Search

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Titanium dioxide nanoparticles (TiO 2 -NPs) are widely used in food, paint, coating, cosmetic, and composite orthodontic material. As a common food additive, TiO 2 -NPs can accumulate in various organs of human body, but the effect and underlying mechanism of bone remain unclear. Here mice were exposed to TiO 2 -NPs by oral gavage, and histological staining of femoral sections showed that TiO 2 -NPs reduced bone formation and enhanced osteoclast activity and lipogenesis, contributing to decreased trabecula bone. Transmission electron microscope (TEM) as well as biochemical and flow cytometry analysis of osteoblast exhibited that TiO 2 -NPs accumulated in osteoblast cytoplasm and impaired mitochondria ultrastructure with increased reactive oxygen species (ROS) and lipid hyperoxide, resulting in osteoblast apoptosis. In terms of mechanism, TiO 2 -NPs treatment inhibited expression of AKT and then increased pro-apoptotic protein Bax expression which was failure to form heterodimers with decreased anti-apoptotic Bcl-2, activating downstream Caspase-9 and Caspase-3 and inducing apoptosis. Additionally, TiO 2 -NPs suppressed Wnt3a level and then activated anti-Glycogen synthesis kinase (GSK-3β) phosphorylation, and ultimately resulted in degradation of β-catenin which down-regulated Runt-related transcription factor 2 (Runx2) and Osterix, inhibiting expression of osteogenic related proteins. Together, these results revealed that exposure of TiO 2 -NPs induced apoptosis and inhibited osteoblast differentiation through suppressing PI3K/AKT and Wnt/β-catenin signaling pathways, resulting in reduction of trabecula bone., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to decrease learning and memory of animals. However, whether the impacts of these NPs on the recognition function are involved in hippocamal neuron damages is poorly understood. In this study, primary cultured hippocampal neurons from one-day-old fetal Sprague-Dawley rats were exposed to 5, 15, or 30 µg/mL TiO2 NPs for 24 h, we investigated cell viability, ultrastructure, and mitochondrial membrane potential (MMP), calcium homeostasis, oxidative stress, antioxidant capacity, apoptotic signaling pathway associated with the primary cultured hippocamal neuron apoptosis. Our findings showed that TiO2 NP treatment resulted in reduction of cell viability, promoted lactate dehydrogenase release, apoptosis, and increased neuron apoptotic rate in a dose-dependent manner. Furthermore, TiO2 NPs led to [Ca(2+)]i elevation, and MMP reduction, up-regulated protein expression of cytochrome c, Bax, caspase-3, glucose-regulated protein 78, C/EBP homologous protein and caspase-12, and down-regulated bcl-2 expression in the primary cultured hippocampal neurons. These findings suggested that hippocampal neuron apoptosis caused by TiO2 NPs may be associated with mitochondria-mediated signal pathway and endoplasmic reticulum-mediated signal pathway., (© 2014 Wiley Periodicals, Inc.)

Objective: To investigate the effects of histone deacetylase 2 (HDAC2) expression on cell proliferation, apoptosis and migration of laryngeal squamous cell carcinoma (LSCC) Hep-2 cells., Methods: HDAC2 siRNA and control siRNA were transfected into LSCC Hep-2 cells by lipofectamine 2000, and cells were divided into three experimental groups: untreated group, control siRNA group and HDAC2 siRNA transfection group. Western blotting was utilized to detect the expression of HDAC2 protein in Hep-2 cells. Cell proliferation and apoptosis were investigated by CCK-8 kit and flow cytometry, respectively. Boyden chamber was used to study cell migration. Expressions of cell apoptosis and cell migration related proteins were detected by Western blotting., Results: HDAC2 siRNA significantly down-regulated the expression of HDAC2 protein in LSCC Hep-2 cells. Down-regulation of HDAC2 expression coincided with an inhibition of cell proliferation and migration along with an induced cell apoptosis of Hep-2 cells. Moreover, down-regulation of HDAC2 expression significantly increased the expressions of caspase-3 and caspase-9 proteins but decreased the expressions of matrix metalloproteinases (MMP)-2 and MMP-9 proteins., Conclusions: HDAC2 may play a pivotal role in the initiation and development of LSCC. Down-regulation of HDAC2 expression mediates cell apoptosis. Cell migration inhibition may be tightly associated with overexpression of caspase-3 and caspase-9 along with down-regulation of MMP-2 and MMP-9 expressions.

Background and Objectives: Stathmin plays a critical role in the regulation of mitosis and mediates the development of malignant tumors. Here, we investigated the potential role of stathmin in cell cycle and apoptosis in esophageal squamous cell carcinoma (ESCC)., Methods: A stathmin short hairpin RNA (shRNA) plasmid was employed to downregulate stathmin expression in the ESCC cell line EC9706 cells. Cell proliferation was measured by cell counting, MTT, and colony formation assay. Cell migration was measured by Boyden chamber. Western blot was used to analyze the expressions of stathmin, survivin, and apoptosis-related proteins in transfected cells. Cell cycle and apoptosis were determined by flow cytometry and DNA ladder. Oncogenicity assay in nude mice was utilized to analyze phenotypic changes of transfected cells in vivo., Results: After transfection with stathmin shRNA plasmid, stathmin expression markedly decreased in EC9706 cells. Stathmin downregulation significantly inhibited cell proliferation, cell migration in vitro, and tumorigenicity in vivo, meanwhile arrested cell cycle in the G2/M phase and induced cell apoptosis. Further, stathmin downregulation resulted in downregulation of Bcl-2 and survivin proteins, activation of Caspase-3., Conclusions: These findings demonstrate that stathmin may play an essential role in carcinogenesis of ESCC, which will lay a foundation for target therapy of ESCC., (Copyright © 2011 Wiley-Liss, Inc.)

Apoptotic effects of oleanolic acid (OA) and ursolic acid (UA) on human liver cancer HepG2, Hep3B, Huh7 and HA22T cell lines were examined. OA or UA at 2, 4, 8 micromol/L were used and their effects on cell viability, DNA fragmentation, mitochondrial membrane potential (MMP), activity of Na(+)-K(+)-ATPase, caspase-3 and caspase-8, cell adhesion, level of intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) in these cell lines were determined. OA or UA treatments concentration-dependently decreased cell viability and increased DNA fragmentation in HepG2 and Hep3B cell lines (P<0.05). However, these two compounds reduced viability and increased DNA fragmentation in Huh7 cell only at 4 and 8 micromol/L (P<0.05). OA or UA treatments concentration-dependently lowered MMP in HepG2, Hep3B and HA22T cell lines (P<0.05). These two compounds also concentration-dependently diminished Na(+)-K(+)-ATPase activity and VEGF level in four test cell lines (P<0.05). Besides Huh7 cell, OA or UA treatments concentration-dependently elevated caspase-3 and caspase-8 activities in other three cell lines (P<0.05). Besides HA22T cell, these two compounds concentration-dependently inhibited cell adhesion and decreased ICAM-1 level in other three cell lines (P<0.05). These findings support that OA and UA are potent anti-cancer agents to cause apoptosis in these liver cancer cell lines., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat H9c2 or L-02 cells for 48 h at 37 °C initially, followed by exposure to ethanol at 150 mM for 24 h at 37 °C. Results showed that the content of assessed phytochemicals was in the range of 1019--2045 mg/100 g dry weight. Flavonoids and triterpenoids were two major detected phytochemicals in SDF. SDF treatments at 0.5% and 1% increased the viability of H9c2 cells, but at three concentrations enhanced the survival of L-02 cells. SDF at 0.5% and 1% up-regulated Bcl-2 messenger RNA (mRNA) expression and down-regulated Bax mRNA expression. Ethanol increased reactive oxygen species production, decreased glutathione content, as well as lowered glutathione peroxidase and catalase activities. SDF treatments reversed these changes. SDF at 0.5% and 1% reduced the activity of cytochrome P450 2E1 and nicotinamide adenine dinucleotide phosphate oxidase, limited p47phox mRNA expression, as well as enhanced factor E2-related factor 2 and heme oxygenase-1 mRNA expression. SDF at three con-centrations decreased gp91phox mRNA expression. In conclusion, these novel findings indicated that SDF aqueous extract was rich in phytochemicals and provided anti-apoptotic and anti-oxidative actions to protect cardiac and hepatic cells against ethanol. Thus, SDF might be considered as a functional food with multiple bio-activities. [ABSTRACT FROM AUTHOR]

Abstract The purpose of present HUVE cells and mice study was to investigate the combined effects of carnosine and asiatic acid (AA) against diabetic progression. In HUVE cells, high glucose decreased cell viability, reduced Bcl-2 mRNA expression and increased Bax mRNA expression. The co-treatment of 0.5 μM carnosine plus 0.5 μM AA led to greater cell viability and Bcl-2 mRNA expression than 1 μM carnosine or 1 μM AA treatment alone. This combination more significantly decreased the production of DNA fragmentation, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nuclear factor kappa B binding activity than carnosine or AA treatment alone. In diabetic mice, the combination of 0.25% carnosine plus 0.25% AA in diet resulted in higher final body weight, and lower levels of plasma glucose and triglyceride than 0.5% carnosine or 0.5% AA treatment alone. Carnosine and AA combination caused more reduction in renal levels of leukin-6, TNF-alpha and ROS than carnosine or AA treatment alone. This combination also more significantly limited renal cyclooxygenase-2 activity and p-p38 phosphorylation than carnosine or AA treatment alone. These novel findings support that this combination is a more powerful remedy for diabetic control. Graphical abstract Effects of carnosine (Car) and/or AA upon NF-κB p50/65 binding activity (OD value/mg protein). HUVE cells were pre-treated with 1 μM Car, 1 μM AA or 0.5 μM Car+0.5 μM AA for 24 h incubation at 37 °C. Then, cells were treated with DMEM containing high glucose (33 mM), and followed by incubating for another 24 h at 37 °C. Normal group had no Car, AA, or high glucose. Control group had no Car or AA, but with high glucose. Data are mean ± SD (n = 6). Values with different alphabet among bars are significantly different at P < 0.05 as analyzed by Dunnett's t -test. Image 1 Highlights • HUVE cell line and diabetic mice were used to examine the combined effects of carnosine and asiatic acid (AA). • Co-treatment of carnosine plus AA led to grater HUVE cell viability and Bcl-2 mRNA expression. • In diabetic mice, carnosine and AA combination caused more reduction in renal IL-6, TNF-alpha and ROS generation. • This combination led to more decrease in renal cyclooxygenase-2 activity and p-p38 phosphorylation. • These findings support that this combination is a powerful remedy for diabetic control. [ABSTRACT FROM AUTHOR]

The biologically active form of vitamin D 3 (1,25(OH) 2 D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D 3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D 3 metabolism has been identified in patients with breast cancer, implying that disruption of 1,25(OH) 2 D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1,25(OH) 2 D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D 3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D 3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D 3 , while elevation of Cyp24a1 levels increases degradation of 1,25(OH) 2 D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D 3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of vitamin D 3 signaling and suggest that activation or restoration of the vitamin D 3 regulated pathway is a potential approach for human breast cancer prevention. [ABSTRACT FROM AUTHOR]

Apoptotic, anti-invasive and anti-migratory effects of maslinic acid (MA) at 4, 8, or 16 µM in human esophageal squamous cancer cell line, OE33; gastric cancer cell line, SGC-7901; and pancreatic cancer cell line, Panc-1, were examined. MA treatments inhibited OE33 and SGC-7901 cells growth at 21–66% and 32–75%, respectively; but lowered Panc-1 viability at 13–27% only. MA treatments increased cleaved caspase-3 and Bax expression, and raised caspase-3 and caspase-8 activities in OE33 and SGC-7901 cells. MA treatments also increased DNA fragmentation and decreased reactive oxygen species production in these two cell lines. MA treatments declined invasion and migration in OE33 and SGC-7901 cells, and lowered vascular endothelial growth factor and transforming growth factor-beta1 levels in these cells. MA suppressed hypoxia-inducible factor-1alpha, matrix metalloproteinase (MMP)-2 and MMP-9 expression in OE33 and SGC-7901 cells. These findings indicated that this triterpene was a potent agent against esophagus and stomach cancers. [ABSTRACT FROM AUTHOR]

Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure. [ABSTRACT FROM AUTHOR]

Study Design: The effect of amlodipine (AM) on spinal cord injury (SCI) and autophagy was researched by establishing ventral spinal cord cells (VSC4.1) oxygen and glucose deprivation model and SCI mice model.Objective: To determine the neuroprotective effects of AM by upregulating autophagy during SCI repair.Summary Of Background Data: AM, an antihypertensive medication, has been shown in several studies to inhibit neuronal apoptosis and exert neuroprotective effects in various central nervous system diseases. However, its effects on SCI are unexplored. Autophagy could inhibit cell apoptosis, which has been shown to promote SCI repair. However, the role of AM in autophagy remains unclear.Methods: We examined the relationship between AM, apoptosis, and autophagy in ventral spinal cord cells and the injured spinal cords of C57BL/6 female mice respectively, following histological, behavioral, microscopic, immunofluorescence, and western blotting analyses.Results: We found that AM could inhibit motor neuronal apoptosis in vitro. Furthermore, AM promoted locomotor recovery by upregulating autophagy and alleviating apoptosis, neuronal loss, and spinal cord damage after SCI.Conclusion: AM inhibited motoneuronal apoptosis by upregulating autophagy to improve SCI recovery. [ABSTRACT FROM AUTHOR]

Apoptotic, anti-invasive and anti-migratory effects of maslinic acid (MA) at 4, 8, or 16 µM in human esophageal squamous cancer cell line, OE33; gastric cancer cell line, SGC-7901; and pancreatic cancer cell line, Panc-1, were examined. MA treatments inhibited OE33 and SGC-7901 cells growth at 21–66% and 32–75%, respectively; but lowered Panc-1 viability at 13–27% only. MA treatments increased cleaved caspase-3 and Bax expression, and raised caspase-3 and caspase-8 activities in OE33 and SGC-7901 cells. MA treatments also increased DNA fragmentation and decreased reactive oxygen species production in these two cell lines. MA treatments declined invasion and migration in OE33 and SGC-7901 cells, and lowered vascular endothelial growth factor and transforming growth factor-beta1 levels in these cells. MA suppressed hypoxia-inducible factor-1alpha, matrix metalloproteinase (MMP)-2 and MMP-9 expression in OE33 and SGC-7901 cells. These findings indicated that this triterpene was a potent agent against esophagus and stomach cancers.

Purpose Observe how specific small RNA interference (siRNA) aimed at TPX2 gene suppresses TPX2 gene expression in esophageal cancer EC9706 cells and the effect on esophageal cancer cell growth and invasion ability. Methods Transfect TPX2 siRNA into EC9706 cells via lipofectamin 2000. The experiments were divided into three groups, a negative control, a blank control and an siRNA interference group (24 h, 48 h, 72 h, 96 h). We examined RNA and protein level alteration of the TPX2 gene after TPX2 siRNA transfection by RT-PCR and Western blot analysis. Detection of how TPX2 siRNA influences EC9706 cell proliferation was done by MTT, cell apoptosis monitored through Tunel assay, in vitro invasion ability via Boyden chamber and cell cycle change by flow cytometry. Results After effective siRNA transfection, TPX2 mRNA and protein expression level in siRNA interference group were (0.31 ± 0.08, 0.39 ± 0.12),72 h after transfection, significantly lower than blank control group (1.00 ± 0.01) and negative control group (0.98 ± 0.11), ( F = 71.182, t 1 = 8.17, t 2 = 7.90, P < 0.05); MTT results demonstrated that cell growth and proliferation were inhibited and the inhibition rate was up to 35.4% ( P < 0.05) compared with the control group. TUNEL results indicated that cell apoptosis index in siRNA interference group was 18.28 ± 0.35, higher than that in blank control group (4.07 ± 0.26)and negative control group (4.13 ± 0.22), ( F = 244.5, t 1 = 60.61, t 2 = 53.32, P < 0.01). Boyden chamber results showed that the transmembrane cell number was 45.30 ± 8.08 in siRNA interference group, less than blank control group (121.90 ± 7.83), ( F = 122.46, t 1 = 11.81, t 2 = 10.47, P < 0.01); besides, in siRNA interference group cell invasion inhibition rate was 71.42 ± 9.12, higher than negative control group (5.65 ± 3.55), ( t = 14.256, P < 0.01). Flow cytometry results illustrated that more EC9706 cells went into apoptosis and cell cycle arrested in S phase. Similar results were obtained by in vivo transplantation, as TPX2 siRNA transfection significantly reduced tumor growth of the xenograft in nude mice. Conclusion siRNA could effectively inhibit the invasion and metastasis of EC9706 cells, promote the apoptosis of tumor cells and may become a new approach for treatment of esophageal carcinoma. [ABSTRACT FROM AUTHOR]