Neobaicalein prevents isoflurane anesthesia-induced cognitive impairment in neonatal mice via regulating CREB1

Abstract Objectives: Isoflurane (ISO) is widely used in the clinic and research. The authors aimed to explore whether Neobaicalein (Neob) could protect neonatal mice from ISO-induced cognitive damage. Method: The open field test, Morris water maze test, and tail suspension test was performed to assess the cognitive function in mice. Enzyme-linked immunosorbent assay was used to evaluate inflammatory-related protein concentrations. Immunohistochemistry was used to assess Ionized calcium-Binding Adapter molecule-1 (IBA-1) expression. Hippocampal neuron viability was detected using the Cell Counting Kit-8 assay. Double immunofluorescence staining was employed to confirm the interaction between proteins. Western blotting was used to assess protein expression levels. Results: Neob notably improved cognitive function and exhibited anti-inflammatory effects; moreover, under isotreatment, it exhibited neuroprotective effects. Furthermore, Neob suppressed interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels and upregulated interleukin-10 levels in ISO-treated mice. Neob significantly mitigated iso-induced increases in IBA-1 - positive cell numbers of the hippocampus in neonatal mice. Furthermore, it inhibited ISO-induced neuronal apoptosis. Mechanistically, Neob was observed to upregulate cAMP Response Element Binding protein (CREB1) phosphorylation and protected hippocampal neurons from ISO-mediated apoptosis. Moreover, it rescued ISO-induced abnormalities of synaptic protein. Conclusions: Neob prevented ISO anesthesia-induced cognitive impairment by suppressing apoptosis and inflammation through upregulating CREB1.

Effect of Chahuang ointment on prevention of phlebitis from peripherally inserted central catheter: randomized clinical trial / Efeito da pomada Chahuang na prevenção de flebite de cateter central inserido perifericamente: ensaio clínico randomizado / Efecto de la pomada de Chahuang en la prevención de la flebitis por catéter central insertado periféricamente: ensayo clínico aleatorizado

ABSTRACT Objective: To assess the effect of Chahuang ointment, a Chinese herbal ointment, on the prevention of phlebitis in patients with peripherally inserted central catheters. Method: This was a multicenter randomized controlled trial, with 171 eligible patients randomly assigned into one of three groups: the Chahuang ointment group, the Mucopolysaccharide Polysulfate cream group, and the control group. The degrees of vein injuries at 72 hours after peripherally inserted central catheter insertion were the primary outcome. Secondary outcomes were the vascular wall thickness, tissue edema and microthrombus evaluated by Color Doppler Flow Imaging, the vascular endothelial growth factor, and endothelin-1 (ET-1) expression in vivo. Results: Compared with the control group, the Chahuang ointment group showed significantly lower incidence of postoperative phlebitis, tissue edema, and microthrombus at 72 hours after peripherally inserted central catheter insertion (all P<0.01). The VEGF and ET-1 expression were significantly inhibited in the Chahuang ointment group after 3 days of treatment (both P<0.01). There were no statistical differences in the degree of vein injuries, microthrombus, or tissue edema between the Chahuang ointment and mucopolysaccharide polysulfate groups (all P>0.05). Conclusion: Chahuang ointment was shown to provide effective prevention and protection against phlebitis after peripherally inserted central catheter insertion.

RESUMO Objetivo: Avaliar o efeito da pomada Chahuang, uma pomada à base de ervas chinesas, na prevenção de flebite em pacientes com cateter central de inserção periférica. Método: Este foi um estudo multicêntrico randomizado controlado, com 171 pacientes elegíveis aleatoriamente designados em um de três grupos: o grupo de pomada Chahuang, o grupo de creme de polissulfato de mucopolissacarídeo e o grupo de controle. Os graus de lesões das veias em 72 horas após a inserção do cateter central perifericamente inserido foram o resultado primário. Os desfechos secundários foram a espessura da parede vascular, edema tecidual e microtrombos avaliados por Color Doppler Flow Imaging, o fator de crescimento endotelial vascular e a expressão da endotelina-1 (ET-1) in vivo. Resultados: Comparado com o grupo controle, o grupo de pomada Chahuang apresentou incidência significativamente menor de flebite pós-operatória, edema de tecido e microtrombos 72 horas após a inserção do cateter central inserido perifericamente (todos P <0,01). A expressão de VEGF e ET-1 foi significativamente inibida no grupo de pomada Chahuang após 3 dias de tratamento (ambos P <0,01). Não houve diferenças estatísticas no grau de lesões das veias, microtrombos ou edema de tecido entre os grupos de pomada de Chahuang e polissulfato de mucopolissacarídeo (todos P> 0,05). Conclusão: A pomada Chahuang demonstrou fornecer prevenção e proteção eficazes contra flebite após a inserção do cateter central perifericamente inserido.

RESUMEN Objetivo: Evaluar el efecto de la pomada Chahuang, una pomada herbal china, sobre la prevención de la flebitis en pacientes con catéteres centrales insertados periféricamente. Método: Este fue un ensayo controlado aleatorio multicéntrico, con 171 pacientes elegibles asignados al azar en uno de tres grupos: el grupo de ungüento Chahuang, el grupo de crema de polisulfato de mucopolisacárido y el grupo de control. Los grados de lesiones de las venas a las 72 horas después de la inserción del catéter central insertado periféricamente fueron el resultado primario. Los resultados secundarios fueron el grosor de la pared vascular, el edema tisular y el microtrombo evaluados por imágenes de flujo con Doppler en color, el factor de crecimiento endotelial vascular y la expresión de endotelina-1 (ET-1) in vivo. Resultados: En comparación con el grupo de control, el grupo de ungüento Chahuang mostró una incidencia significativamente menor de flebitis posoperatoria, edema tisular y microtrombos a las 72 horas después de la inserción del catéter central insertado periféricamente (todos P <0,01). La expresión de VEGF y ET-1 se inhibió significativamente en el grupo de pomada de Chahuang después de 3 días de tratamiento (ambos P <0,01). No hubo diferencias estadísticas en el grado de lesiones venosas, microtrombos o edema tisular entre los grupos de pomada de Chahuang y polisulfato de mucopolisacárido (todos P> 0,05). Conclusión: Se demostró que la pomada de Chahuang proporciona una prevención y protección eficaces contra la flebitis después de la inserción de un catéter central insertado periféricamente.

NF-E2: a novel regulator of alpha-hemoglobin stabilizing protein gene expression / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether α-hemoglobin stabilizing protein (AHSP), the α-globin-specific molecular chaperone, is regulated by erythroid transcription factor NF-E2.</p><p><b>METHODS</b>We established the stable cell line with NF-E2p45 (the larger subunit of NF-E2) short hairpin RNA to silence its expression. Western blot, real-time polymerase chain reaction, and chromatin immunoprecipitation (ChIP) analysis were performed to detect the expression of AHSP, the histone modifications at AHSP gene locus, and the binding of GATA-1 at the AHSP promoter with NF-E2p45 deficiency. ChIP was also carried out in dimethyl sulfoxide (DMSO)-induced DS19 cells and estrogen-induced G1E-ER4 cells to examine NF-E2 binding to the AHSP gene locus and its changes during cell erythroid differentiation. Finally, luciferase assay was applied in HeLa cells transfected with AHSP promoter fragments to examine AHSP promoter activity in the presence of exogenous NF-E2p45.</p><p><b>RESULTS</b>We found that AHSP expression was highly dependent on NF-E2p45. NF-E2 bound to the regions across AHSP gene locus in vivo, and the transcription of AHSP was transactivated by exogenous NF-E2p45. In addition, we observed the decrease of H3K4 trimethylation and GATA-1 occupancy at the AHSP gene locus in NF-E2p45-deficient cells. Restoration of GATA-1 in G1E-ER4 cells in turn led to increased DNA binding of NF-E2p45.</p><p><b>CONCLUSION</b>NF-E2 may play an important role in AHSP gene regulation, providing new insights into the molecular mechanisms underlying the erythroid-specific expression of AHSP as well as new possibilities for β-thalassemia treatment.</p>

Epigenetic repression of SATB1 by polycomb group protein EZH2 in epithelial cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the regulatory mechanism of SATB1 repression in cells other than T cells or erythroid cells, which have high expression level of SATB1.</p><p><b>METHODS</b>HeLa epithelial cells were treated with either histone deacetylase inhibitor (HDACi) trichostatin A (TSA) or DNA methylation inhibitor 5-Aza-C before detecting SATB1 expression. Luciferase reporter system was applied to measure effects of EZH2 on SATB1 promoter activity. Over-expression or knockdown of EZH2 and subsequent quantitative reverse transcription-polymerase chain reaction were performed to determine the effect of this Polycomb group protein on SATB1 transcription. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of EZH2 and trimethylated H3K27 (H3K27me3) at SATB1 promoter in HeLa cells. K562 cells and Jurkat cells, both having high-level expression of SATB1, were used in the ChIP experiment as controls.</p><p><b>RESULTS</b>Both TSA and 5-Aza-C increased SATB1 expression in HeLa cells. Over-expression of EZH2 reduced promoter activity as well as the mRNA level of SATB1, while knockdown of EZH2 apparently enhanced SATB1 expression in HeLa cells but not in K562 cells and Jurkat cells. ChIP assay Results suggested that epigenetic silencing of SATB1 by EZH2 in HeLa cells was mediated by trimethylation modification of H3K27. In contrast, enrichment of EZH2 and H3K27me3 was not detected within proximal promoter region of SATB1 in either K562 or Jurkat cells.</p><p><b>CONCLUSION</b>SATB1 is a bona fide EZH2 target gene in HeLa cells and the repression of SATB1 by EZH2 may be mediated by trimethylation modification on H3K27.</p>