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41.
The available drug therapy for post-ischemic neurodegeneration of the brain is symptomatic. This review provides an evaluation of possible dietary therapy for post-ischemic neurodegeneration with myricetin. The purpose of this review was to provide a comprehensive overview of what scientists have done regarding the benefits of myricetin in post-ischemic neurodegeneration. The data in this article contribute to a better understanding of the potential benefits of myricetin in the treatment of post-ischemic brain neurodegeneration, and inform physicians, scientists and patients, as well as their caregivers, about treatment options. Due to the pleiotropic properties of myricetin, including anti-amyloid, anti-phosphorylation of tau protein, anti-inflammatory, anti-oxidant and autophagous, as well as increasing acetylcholine, myricetin is a promising candidate for treatment after ischemia brain neurodegeneration with full-blown dementia. In this way, it may gain interest as a potential substance for the prophylaxis of the development of post-ischemic brain neurodegeneration. It is a safe substance, commercially available, inexpensive and registered as a pro-health product in the US and Europe. Taken together, the evidence available in the review on the therapeutic potential of myricetin provides helpful insight into the potential clinical utility of myricetin in treating neurodegenerative disorders with full-blown dementia. Therefore, myricetin may be a promising complementary agent in the future against the development of post-ischemic brain neurodegeneration. Indeed, there is a scientific rationale for the use of myricetin in the prevention and treatment of brain neurodegeneration caused by ischemia. 相似文献
42.
ukasz Kopiasz Katarzyna Dziendzikowska Magorzata Gajewska Micha Oczkowski Kinga Majchrzak-Kuligowska Tomasz Krlikowski Joanna Gromadzka-Ostrowska 《Nutrients》2021,13(2)
Background: Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model. Methods: A total of 150 Sprague–Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG−) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot. Results: The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days. Conclusions: Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD. 相似文献
43.
This study was to explore the effect and mechanism of Probucol on STZ-induced erectile dysfunction in diabetic rats. Thirty SD male rats aged 12 weeks were given intraperitoneal injection of STZ after fasting for 12 hr. Diabetic rats were haphazardly partitioned under two assemblies and administered 0 or 500 mg/kg probucol by oral gavage to 12 weeks. Control group was intraperitoneally injected with physiological saline, and saline was administered by oral gavage daily. Intracorporeal pressure was used to evaluate erectile function. Levels of proteins were detected using immunohistochemistry and Western blotting. α-SMA and vWF were detected using immunofluorescence staining. After treatment, erectile function in probucol group was significantly improved. Endoplasmic reticulum stress-related proteins were expressed higher in DM group than in sham group, while expression of these proteins decreased significantly in probucol group. However, α-SMA and vWF were expressed at lower levels in DM group than in sham group, and probucol treatment reversed this phenomenon. Finally, Bax and Caspase3 were expressed at higher levels and Bcl-2 was expressed at lower levels in DM group, while the opposite result was obtained in probucol group. In conclusions, probucol improves erectile function by reducing endothelial dysfunction and inhibiting PERK/ATF4/CHOP pathway in STZ-induced diabetic rats. 相似文献
44.
目的探讨牛磺酸(NHS)对老年大鼠骨量流失的影响,并探讨可能的机制。方法将30只大鼠随机分为对照组(CON)、模型组(MOD)以及牛磺酸组(NHS),每组10只;其中NHS组大鼠每天接受牛磺酸(2 g/kg)治疗12周;待治疗结束后通过Micro-CT检测、HE染色切片、血清指标、蛋白质印迹观察治疗效果,探讨可能的机制。结果治疗12周后,与MOD组相比,三点弯曲试验、Micro-CT和HE染色切片结果显示NHS组大鼠的骨小梁数量、骨强度和骨密度(bone mineral density,BMD)得到明显改善。NHS组大鼠最大载荷和弹性模量、BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。和MOD组比较,NHS治疗后大鼠血清BLAP、P1NP、TRACP-5b和β-CTX水平明显降低,组间差异有统计学意义(P<0.05)。和MOD组比较,NHS组Runx2、BMP2、Beclin-1和LC3Ⅱ/LC3-Ⅰ表达水平明显上调,而P62表达水平显著下调,比较差异有统计学意义(P<0.05)。结论NHS可能通过激活自噬,从而对年龄引起的骨量丢失起到保护作用。 相似文献
45.
目的 研究Homer1b/c蛋白在谷氨酸诱发的细胞自噬中的作用及机制。方法 选用小鼠海马细胞系HT22细胞,通过500 ?mol/L谷氨酸处理建立细胞损伤模型。用siRNA慢病毒转染方式下调Homer1b/c表达和10 ?mol/LBAPTA-AM(1,2-双(2-氨基苯氧基)乙烷-N,N,N`,N`-四乙酸四乙酸甲酯,钙离子螯合剂)、10 mmol/L4-PBA(4-苯基丁酸,内质网应激抑制剂)分别抑制细胞内钙离子释放和内质网应激后,使用蛋白质印迹法检测Homer1b/c,自噬蛋白Beclin-1、微管相关蛋白轻链3(LC3),以及内质网应激标志蛋白CHOP(人内质网应激相关蛋白)、GRP-78(葡萄糖调节蛋白78)的表达水平。每组实验均进行3次,采用独立样本t检验和单因素方差分析进行统计学分析。结果 谷氨酸处理HT22细胞12 h后,Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值均升高(P<0.05),下调Homer1b/c表达可降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度(P<0.05)。抑制细胞内钙离子释放和抑制内质网应激均能降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度(P<0.05)。然而在下调Homer1b/c表达后,抑制细胞内钙离子释放和抑制内质网应激未能进一步降低Beclin-1表达和LC3-Ⅱ/LC3-Ⅰ比值的升高程度(P<0.05)。结论 Homer1b/c能够调节谷氨酸诱导的自噬,其调节作用可能与内质网功能有关。 相似文献
46.
乙酰基二肽-1鲸蜡酯(acetyl dipeptide-1 cetyl ester,AD-1)是乙酸和十六烷基醇与精氨酸和酪氨酸组成的人工合成肽,具有一定的抗炎和提高皮肤屏障功能的作用,已被用于敏感肌化妆品中。该成分虽然也被用于抗衰老化妆品中,但缺乏公开的系统科学研究。本研究通过评价AD-1的体外抗氧化和抗糖基化作用、建立UVA反复照射真皮原代成纤维细胞的光老化模型,探讨其在光老化细胞中的抗衰老活性。采用MTT法测定AD-1对细胞活力的影响;RT-qPCR法检测AD-1和UVA对衰老相关p21、p53、MMPs、IL6、Col1、Col3以及自噬相关p62、ATG5、ATG7 mRNA表达的影响;Western blot法检测AD-1和UVA对衰老及自噬相关p16、p21、p53、Col1、LC3B、p62蛋白水平的影响;β-半乳糖苷酶染色和MDC染色评价细胞衰老损伤,并通过荧光探针DCFH-DA检测细胞内活性氧水平。实验结果显示,AD-1干预可以减少UVA诱导的细胞损伤和mRNA表达异常,改善p16、p21、p53、Col1、LC3B、p62蛋白水平异常。结果表明,AD-1具有一定的... 相似文献
47.
48.
目的:观察在细胞中占在中心地位的内质网在人侵袭性结肠癌细胞中的超微结构特点。方法:收集外科手术切除的结肠癌标本,应用透射电镜技术观察高分化和低分化人侵袭性结肠癌细胞内质网结构。结果:高分化癌细胞呈柱状,排列较整齐。细胞质中的内质网呈多种形状,并常出现不规则扩张。细胞壁底侧的舌状伪足中可见内质网呈囊泡样;分化癌细胞排列拉散,有的几乎与其他细胞脱离,细胞中的内质网减少;有的内质网与质膜融合,但有向外分泌内含物的趋势。结论:观察到的不同分化程度的人侵袭性结肠癌细胞内质网结构特点将可能成为诊断结肠癌的形态学依据。 相似文献
49.
- Recently, 4-chloro-3-ethyl phenol (CEP) has been shown to cause the release of internally stored Ca2+, apparently through ryanodine-sensitive Ca2+ channels, in fractionated skeletal muscle terminal cisternae and in a variety of non-excitable cell types. Its action on smooth muscle is unknown. In this study, we characterized the actions of CEP on vascular contraction in endothelium-denuded dog mesenteric artery. We also determined its ability to release Ca2+, by use of Ca2+ imaging techniques, on dog isolated mesenteric artery smooth muscle cells and on bovine cultured pulmonary artery endothelial cells.
- After phenylephrine-(PE, 10 μM) sensitive Ca2+ stores were depleted by maximal PE stimulation in Ca2+-free medium, the action of CEP on refilling of the emptied PE stores was tested, by first pre-incubating the endothelium-denuded artery in CEP for 15 min before Ca2+ was restored for a 30 min refilling period. At the end of this period, Ca2+ and CEP were removed, and the arterial ring was tested again with PE to assess the degree of refilling of the internal Ca2+ store.
- In a concentration-dependent manner (30, 100 and 300 μM), CEP significantly reduced the size of the post-refilling PE contraction (49.4, 28.9 and 5.7% of control, respectively) in Ca2+-free media. This suggests that Ca2+ levels are reduced in the internal stores by CEP treatment. CEP alone did not cause any contraction either in Ca2+-containing or Ca2+-free Krebs solution.
- Restoring Ca2+ in the presence of PE caused a large contraction, which reflects PE-induced influx of extracellular Ca2+. The contraction of tissues pretreated with 300 μM CEP was significantly less compared with controls. However, tissues pretreated with 30 and 100 μM CEP were unaffected. Washout of CEP over 30 min produced complete recovery of responses to PE in Ca2+-free and Ca2+-containing medium suggesting a rapid reversal of CEP effects.
- Concentration-response curves were constructed for PE, 5-hydroxytryptamine (5-HT) and K+ in the absence of and after 30 min pre-incubation with 30, 100 and 300 μM CEP. In all cases, CEP caused a concentration-dependent depression of the maximum response to PE (84.8, 43.4 and 11.6% of control), 5-HT (65.4, 25.7 and 6.9% of control) and K+ (77.6, 41.1 and 10.8% of control).
- Some arterial rings were pre-incubated with ryanodine (30 μM) for 30 min before the construction of PE concentration-response curves. In Ca2+-free Krebs solution, ryanodine alone did not cause any contraction. However, 58% (11 out of 19) of the tissues tested with ryanodine developed contraction (6.9±1.2% of 100 mM K+ contraction, n=11) in the presence of external Ca2+. EC50 values for PE in ryanodine-treated tissues (1.7±0.25 μM, n=16) were not significantly different from controls (2.5±0.41 μM, n=22). Maximum contractions to PE (118.5±4.4% of 100 mM K+ contraction, n=16) were also unaffected by ryanodine when compared to controls (129±4.2%, n=23).
- When fura-2 loaded smooth muscle cells (n=13) and endothelial cells (n=27) were imaged for Ca2+ distribution, it was observed that 100 and 300 μM CEP in Ca2+-free medium caused Ca2+ release in both cell types. Smooth muscle cells showed a small decrease in cell length. Addition of EGTA (5 mM) reversed the effect of CEP on intracellular Ca2+ to control values.
- These data show, for the first time in vascular smooth muscle and endothelial cells, that CEP releases Ca2+ more rapidly than ryanodine. Unlike ryanodine, CEP caused no basal contraction but depressed contractions to PE, 5-HT and K+. The lack of basal contraction may result from altered responsiveness of the contractile system to intracellular Ca2+ elevation.
50.
Yuansheng Tan Daming Li Renjie Song David Lawrence David O Carpenter 《Toxicological sciences》2003,76(2):328-337
The effects of exposure of acutely dissociated rat thymocytes to various polychlorinated biphenyl (PCB) congeners were examined using flow cytometry. Non-planar, ortho-substituted congeners caused a rapid cell death at low micromolar concentrations, while coplanar, dioxin-like congeners at the same concentration were without significant effect. The most potent of the congeners studied was PCB 52 (2,2',5,5'-tetrachlorobiphenyl), which had an IC50 of 3.96 microM at 20 min. Prior to loss of viability there was a decrease in mitochondrial membrane potential Delta Psi m, an accumulation of intracellular calcium, and a progressive leakiness of the plasma membrane. Application of PCB 52 in calcium-free medium reduced the calcium accumulation, but did not reduce cell death. Agents that depolarized mitochondria also did not induce the same degree of cell death caused by PCB 52. Cyclosporin A, which prevents opening of the mitochondria permeability transition channel, protected against cell death but did not protect against mitochondrial depolarization or calcium accumulation. Rapamycin and FK 506 at high concentration provided partial protection against cell death. These observations indicate that the ortho-substituted PCB 52 disrupts plasma, mitochondrial and endoplasmic reticulum membranes. We hypothesize that PCB 52 incorporates into lipid bilayers and with its bulky, three-dimensional ortho-substituted congener structure disrupts membrane function to a greater degree than coplanar congeners. 相似文献