Retraction to "Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats".

[This retracts the article DOI: 10.1515/biol-2021-0012.].

A novel AlGaN/GaN heterostructure field-effect transistor based on open-gate technology.

In this study, a novel AlGaN/GaN heterostructure field-effect transistor based on open-gate technology was fabricated. Sample transistors of different structures and sizes were constructed. Through measurements, it was found that by changing the width of the opening, the threshold voltage of the device could be easily modulated across a larger range. The open-gate device had two working modes with different transconductance. When the gate-source voltage VGS ≤ - 4.5 V, only the open region was conductive, and a new working mechanism modulated the channel current. Corresponding theoretical analysis and calculations showed that its saturation mechanism was related to a virtual gate formed by electron injection onto the surface. Also, the gate-source voltage modulated the open channel current by changing the channel electron mobility through polarization Coulomb field scattering. When used as class-A voltage amplifiers, open-gate devices can achieve effective voltage amplification with very low power consumption.

Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats.

Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1ß, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.

LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway.

Glioblastoma multiforme (GBM) brings serious physical and psychological pain to GBM patients, whose survival rate remains not optimistic. Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of many cancers, including GBM. However, the mechanism and function of long intergenic non-protein coding RNA 1152 (LINC01152) in GBM are still unclear. In our study, we aimed to explore the function and mechanism of LINC01152 in GBM. Then qRT-PCR analysis was implemented to search the expression of RNAs in GBM tissues and cells. Functional assays such as EdU assay, colony formation assay, TUNEL assay and flow cytometry analysis were conducted to estimate GBM cell proliferation and apoptosis. RNA pull down assay, luciferase reporter assay, RIP and ChIP assays were implemented to search the binding between molecules. As a result, we discovered that LINC01152 was upregulated in GBM tissues and cells. LINC01152 and mastermind like transcriptional coactivator 2 (MAML2) could both play the oncogenic part in GBM. Moreover, LINC01152 positively regulated MAML2 in GBM by sponging miR-466 and recruiting SRSF1. In turn, RBPJ/MAML2 transcription complex was found to activate the transcription of LINC01152 in GBM cells. In conclusion, LINC01152 could upregulate the expression of MAML2 to promote tumorigenesis in GBM via Notch signaling pathway.

Correlation Between SNPs at the 3'UTR of the FGF2 Gene and Their Interaction with Environmental Factors in Han Chinese Diabetic Peripheral Neuropathy Patients.

FGF2 is a neurotrophic factor that can act as a key regulatory molecule of neuroprotection, neurogenesis, and angiogenesis in various injuries. To explore the genetic background of the FGF2 gene on DPN development, this study analyzed the correlation between SNPs in the 3'UTR of the FGF2 gene and their interaction with environmental factors in DPN patients of Han Chinese nationality. Sanger sequencing was used to analyze the FGF2 genotypes at the rs1048201, rs3804158, rs41348645, rs6854081, rs3747676, rs7683093, rs1476215, and rs1476217 loci in 150 DPN patients, 150 NDPN patients, and 150 healthy control patients. Plasma FGF2 levels were measured in all subjects by using ELISAs. Subjects carrying the T allele at the rs1048201 locus in the FGF2 gene had a significantly lower risk of developing DPN compared with subjects carrying the C allele (OR = 0.43, 95% CI = 0.33-0.56, p < 0.01). Subjects with the G genotype at the rs6854081 locus had an exceptionally higher risk of developing DPN than subjects with the T allele (OR = 1.66, 95% CI = 1.39-1.89, p < 0.01). Individuals harboring the G allele at the rs7683093 locus had a markedly higher risk of DPN than patients with the C allele (OR = 1.63, 95% CI = 1.36-1.87, p < 0.01). Finally, individuals having the A genotype at the rs1476215 locus had a significantly higher risk of DPN than individuals carrying the T allele (OR = 1.82, 95% CI = 1.53-2.02, p < 0.01). There was an interaction between age and alcohol consumption and the SNP rs7683093. SNPs at rs1048201, rs6854081, rs7683093, and rs1476215 in the FGF2 3'UTR were strongly associated with plasma levels of FGF2 (p < 0.05). SNPs at the rs1048201, rs6854081, rs7683093, and rs1476215 loci in the FGF2 gene were significantly associated with the risk of DPN. A possible mechanism is that these SNPs affect the expression level of FGF2 by interrupting the binding of microRNAs to target sites in the 3'UTR.

NCAPG2 facilitates glioblastoma cells' malignancy and xenograft tumor growth via HBO1 activation by phosphorylation.

NCAPG2 (non-SMC condensin II complex subunit G2), as an important factor in cell mitosis, has been the focus in the study of different cancers. However, the role of NCAPG2 in the malignancy of glioblastoma cells remains unknown. The findings from the present study demonstrated that NCAPG2 was significantly increased in human glioblastoma tissues and was associated with poor clinical outcome. Moreover, NCAPG2 could promote proliferation, migration, and invasion and regulate cell cycle in glioblastoma cells. Investigation of the molecular mechanism indicated that NCAPG2 regulated HBO1 phosphorylation and H4 histone acetylase activation, modulated the activation of Wnt/ß-catenin pathway, and the binding of MCM protein to chromatin to exert its role. Furthermore, knockdown of HBO1 was found to reverse the effect of NCAPG2 overexpression on cell proliferation, migration, invasion, and cell cycle. In addition, knockdown of NCAPG2 attenuated glioblastoma tumorigenesis in vivo. Taken together, the findings demonstrated that NCAPG2 facilitates the malignancy of glioblastoma cells and xenograft tumor growth via HBO1 activation by phosphorylation. These results improve our understanding of the mechanism underlying glioblastoma progression and may contribute to the identification of novel biomarkers and therapeutic targets for glioblastoma.

[Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats].

OBJECTIVE: To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury. METHODS: Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 µg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting. RESULTS: Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury (P < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury (P < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury (P < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma (P < 0.05) and increased further at 2 days (P < 0.01); the water content of the brain did not change significantly at 2 h (P > 0.05) but increased significantly 2 d after the injury (P < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma (P < 0.01). CONCLUSIONS: Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

B-cell CLL/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway.

Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues. Furthermore, high expression of BCL3 protein was confirmed by immunoblotting in glioma cells as compared with normal human astrocyte cell line. The positive expression of BCL3 was correlated with adverse prognostic features and reduced overall survival rate of glioma patients. BCL3 silencing resulted in prominent decreased proliferation, cell cycle arrest in G1 phase and increased apoptosis in U251 cells. In contrast, BCL3 overexpression in U87 cells remarkably facilitated proliferative ability and cell cycle progression and induced apoptosis. In vivo studies showed that BCL3 knockdown inhibited the tumor growth of U251 cells in a mouse xenograft model. Mechanistically, BCL3 positively regulated the abundance of STAT3, p-STAT3 and the downstream targets of STAT3 pathway including BCL2, MCL-1 and cyclin D1 in glioma cells. Furthermore, a positive correlation between BCL3 and STAT3 expression was observed in glioma specimens. Notably, we confirmed that STAT3 knockdown abolished the oncogenic roles of BCL3 in glioma. In conclusion, we suggest that BCL3 serves as an oncogene in glioma by modulating proliferation, cell cycle progression and apoptosis, and its oncogenic effects are mediated by the STAT3 signaling pathway.