Identification, structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors.

During the analysis of benziamidazole-class irreversible proton pump inhibitors, an unusual mass spectral response with the mass-to-charge ratio at [M+10]+ intrigued us, as it couldn't be assigned to any literature known relevant structure, intermediate or adduct ion. Moreover, this mysterious mass pattern of [M+10]+ has been gradually observed by series of marketed proton pump inhibitors, viz. omeprazole, pantoprazole, lansoprazole and rabeprazole. All the previous attempts to isolate the corresponding component were unsuccessful. The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate (10), which is the common fragment ion of series of labile aggregates. The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation. These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization. The structure of the corresponding pyridinium thiocyanate species of omeprazole (10a) has been eventually characterized with the help of synthetic specimen (10a'). Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance, chemical derivatization and colorimetric experiments.

Effect of Comprehensive Nursing Intervention on the Effect of CT-Guided Intravenous Thrombolysis in Acute Cerebral Infarction.

OBJECTIVE: To investigate the effect of comprehensive nursing intervention on the effect of CT-guided intravenous thrombolytic therapy for acute cerebral infarction. METHODS: 99 patients with acute cerebral infarction in the internal carotid artery system who were hospitalized in our department from December 2019 to December 2020 with an onset of 3-9 h were selected and randomly divided into two groups. All patients underwent multimode CT examinations and received rt-PA thrombolytic therapy. 52 patients with conventional care were included in the control group, and 47 patients with comprehensive nursing intervention were included in the observation group. The influence characteristics, Barthel score, serum MMP-9 level, and NIHSS score were compared between the two groups. RESULTS: After the comprehensive nursing intervention, the total efficiency, total satisfaction, psychological status, and Barthel score of the observation group were significantly higher than those of the control group (P < 0.05). The serum MMP-9 level and NIHSS score were significantly lower than those of the control group (P < 0.05). CONCLUSION: The use of comprehensive nursing interventions in the CT-guided intravenous thrombolysis treatment of ACI patients reduced the degree of neurological impairment, improved the therapeutic effect, increased nursing satisfaction, and enabled better control of the condition of patients with cerebral infarction, which is worth promoting research.

Molecular Mechanism of 73HOXC-AS1-Activated Wntß-Catenin Signaling and eIF4AIII in Promoting Progression of Gastric Cancer.

OBJECTIVE: This study is aimed at exploring the regulatory mechanism of 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eukaryotic initiation factor 4A (eIF4AIII) expression increased by lentivirus-eIF4AIII-RNAi (44682-1) (LV-eIF4AIII-RNAi (44682-1)). METHODS: Focusing on the occurrence and progression of gastric cancer, the human gastric cancer cell line BGC823 (University Experimental Center) was taken as the research object and was transfected after subculture. According to the different ways of transfection, the cells were divided into the P1 group (LV-eIF4AIII-RNAi (44682-1) overexpressed plasmid), the P2 group (pcDNA-HOXC-AS1 overexpressed plasmid), the P3 group (LV-eIF4AIII-RNAi (44682-1) + pcDNA-HOXC-AS1), and the P4 group (no transfection, control group). Cell proliferation was detected by CCK-8 (Cell Counting Kit-8) assay, Western blotting was adopted to detect Wnt3a and P-GSK3ß proteins, Transwell assay was adopted to detect the ability of cell migration and invasion, and cell cycle and apoptosis were detected by flow cytometry. RESULTS: The results show that the protein expression levels of Wnt3a and P-GSK3ß (glycogen synthase kinase-3ß) in the P1 and P4 groups were lower than those in the P2 and P3 groups (P < 0.05). The cell activity and clone number of BGC823 in the P3 group were higher than those in the P1, P2, and P4 groups (P < 0.05). The apoptosis rate of BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups (P < 0.05). The proportion of BGC823 cells in the P3 group at the S phase was significantly higher than those in the P1, P2, and P4 groups, while the proportion in the G2 phase was significantly lower than those in the P1, P2, and P4 groups (P < 0.05). The number of migrating and invading BGC823 cells in the P3 group was significantly higher than those in the P1, P2, and P4 groups, while the number of migrating BGC823 cells in the P4 group was significantly lower than those in the P1 and P2 groups (P < 0.05). CONCLUSION: The 73HOXC-AS1 overexpression plasmid-activated Wntß-catenin classic signaling pathway and eIF4AIII expression increased by LV-eIF4AIII-RNAi (44682-1) could act together on BGC823 cells to improve cell proliferation activity, migration, and invasion; inhibit cell apoptosis; and prevent cells from entering the S phase.

Protective effect of apple polyphenols on chronic ethanol exposure-induced neural injury in rats.

Apple polyphenols (AP) have attracted much attention due to their various bioactivities. In this study, the protective effect of AP against chronic ethanol exposure-induced neural injury as well as the possible mechanisms were investigated. Body weight, daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated. The influences of AP on motor behavior and memory were detected by locomotor activity test, rotarod test, beam walking test, and Y maze test and novel object recognition test, respectively. The changes of blood ethanol concentration and the oxidative stress were also measured. AP improved chronic ethanol exposure-induced the inhibition of body weight and the decrease of daily average food intake, but did not influence the daily average fluid intake and the daily average ethanol intake, indicating that the improve effect of AP did not result from the decrease of ethanol intake. Motor activity and motor coordination were not influenced after chronic ethanol exposure though the blood ethanol concentration was higher than that in control group. AP improved significantly chronic ethanol-induced the memory impairment and the hippocampal CA1 neurons damage. Further studies found that AP decreased the contents of NO and MDA and increased the levels of T-AOC and GSH in the hippocampus of rats. These results suggest that AP exerts a protective effect against chronic ethanol-induced memory impairment through improving the oxidative stress in the hippocampus.

Bioinformatic analysis to explore key genes associated with brain ischemia-reperfusion injury in rats.

Objectives: Ischemia-reperfusion (I/R) injury can aggravate the dysfunction and structural damage of tissues and organs. This study aimed at investigating the pathogenesis of I/R injury. Methods: GSE82146 was extracted from Gene Expression Omnibus database, which included 12 nonischemic control (NIC) hippocampal tissues and 15 complete global brain ischemia (CGBI)-reperfusion hippocampal tissues. After processing the original data using the affy package, the differentially expressed genes (DEGs) between CGBI and NIC samples were analysed by the limma package. An enrichment analysis for the DEGs was implemented based on the MATHT online tool. Using Cytoscape software, a protein-protein interaction (PPI) network was built and significant network modules were obtained. Finally, miRNA-gene pairs were predicted using the miRWalk2.0 tool, and the miRNA-gene regulatory network was built using the Cytoscape software. Results: Overall, 322 DEGs (279 upregulated and 43 downregulated) were present in the CGBI samples. In PPI network, JUN, STAT3, ATF3, VEGFA and ATF4 had higher degrees. Four significant modules (modules a, b, c and d) were obtained from PPI network. Enrichment analysis suggested that FGF2 in module d was involved in MAPK signalling pathway. In the miRNA-gene regulatory network, rno-miR-125a-5p and rno-miR-125b-5p were among the top 10 miRNAs. Conclusion: JUN, STAT3, ATF3, VEGFA, ATF4, FGF2, rno-miR-125a-5p and rno-miR-125b-5p might affect the development and progression of I/R injury.

Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats.

The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats.

Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure.

Microglia function as the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes which are critical component of neurodegenerative diseases. Alcohol abuse has been considered as one of the common reasons for neurodegeneration although the causative factors are poorly understood. Here, we investigated whether activated microglia were implicated in neurodegeneration and cognitive dysfunctions in adult rats after intermittent alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then 3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4 days of ethanol treatments were repeated four times intermittently to simulate the binge drinking of human alcoholics. Neurodegeneration and microglial activation were detected by Fluoro-Jade B staining, Golgi staining, immunohistochemistry and ELISA, respectively, while cognitive function was assessed by Morris water maze and novel object recognition. The results showed that microglial activation and inflammatory cytokine expression were obvious in the parietal association cortex, entorhinal cortex and hippocampus accompanied by neurodegeneration following ethanol treatment. Moreover, learning and memory abilities also declined following ethanol treatments. However, the hypertrophied microglia disappeared accompanied by the decrease of inflammatory cytokines levels on day 4, and ramified microglial proliferated significantly on day 14 after ethanol withdrawal, along with a recovery from neuronal damage and cognitive impairment. Thus, the present study indicated that activated microglia might be involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia appear to have a contribution to the recovery during abstinence.