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Pharmacodynamics and Mechanism of Astragali Radix and Anemarrhenae Rhizoma in Treating Chronic Heart Failure by Inhibiting Complement Activation. 黄芪和知母通过抑制补体激活治疗慢性心力衰竭的药效学和机制
Pub Date : 2024-04-01 DOI: 10.1089/rej.2023.0068
Qi Dai, Shi Zhao, Weihong Li, Kedi Liu, Xingru Tao, Chengzhao Liu, Hong Yao, Fei Mu, Sha Chen, Jing Li, Peifeng Wei, Feng Gao, Miaomiao Xi

Astragali radix (AR) and anemarrhenae rhizoma (AAR) are used clinically in Chinese medicine for the treatment of chronic heart failure (CHF), but the exact therapeutic mechanism is unclear. In this study, a total of 60 male C57BL/6 mice were divided into 5 groups, namely sham, model, AR, AAR, and AR-AAR. In the sham group, the chest was opened without ligation. In the other groups, the chest was opened and the transverse aorta was ligated to construct the transverse aortic constriction model. After 8 weeks of feeding, mice were given medicines by gavage for 4 weeks. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were detected by echocardiography. Heart weight index (HWI) and wheat germ agglutinin staining were used to evaluate cardiac hypertrophy. Hematoxylin-eosin staining was used to observe the pathological morphology of myocardial tissue. Masson staining was used to evaluate myocardial fibrosis. The content of serum brain natriuretic peptide (BNP) was detected by enzyme-linked immunosorbent assay kit. The content of serum immunoglobulin G (IgG) was detected by immunoturbidimetry. The mechanism of AR-AAR in the treatment of CHF was explored by proteomics. Western blot was used to detect the protein expressions of complement component 1s (C1s), complement component 9 (C9), and terminal complement complex 5b-9 (C5b-9). The results show that AR-AAR inhibits the expression of complement proteins C1s, C9, and C5b-9 by inhibiting the production of IgG antibodies from B cell activation, which further inhibits the complement activation, attenuates myocardial fibrosis, reduces HWI and cardiomyocyte cross-sectional area, improves cardiomyocyte injury, reduces serum BNP release, elevates LVEF and LVFS, improves cardiac function, and exerts myocardial protection.

黄芪(AR)和知母(AAR)在中医临床上被用于治疗慢性心力衰竭(CHF),但确切的治疗机制尚不清楚。本研究将 60 只雄性 C57BL/6 小鼠分为 6 组,分别为 Sham 组、Model 组、AR 组、AAR 组和 AR-AAR 组。Sham 组小鼠只开胸、不结扎。其他组小鼠开胸并结扎横向主动脉,构建横向主动脉收缩(TAC)模型。小鼠饲养八周后,灌胃给药四周。通过超声心动图检测左室射血分数(LVEF)和左室缩短分数(LVFS)。心脏重量指数(HWI)和小麦胚芽凝集素(WGA)染色用于评估心脏肥大。苏木精-伊红(HE)染色用于观察心肌组织的病理形态。马森染色用于评估心肌纤维化。用酶联免疫吸附试剂盒检测血清中脑钠肽(BNP)的含量。用免疫比浊法检测血清免疫球蛋白 G(IgG)的含量。通过蛋白质组学探讨了 AR-AAR 治疗 CHF 的机制。采用 Western 印迹法检测补体成分 1s(C1s)、补体成分 9(C9)和末端补体复合物 5b-9(C5b-9)的蛋白表达。结果表明,AR-AAR通过抑制B细胞活化产生的IgG抗体来抑制补体蛋白C1s、C9和C5b-9的表达,从而进一步抑制补体活化,减轻心肌纤维化,降低HWI和心肌细胞横截面积,改善心肌细胞损伤,减少血清BNP释放,提高LVEF和LVFS,改善心功能,发挥心肌保护作用。
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引用次数: 0
Rejuvenation Research Is 20 Years Old! 年轻化研究已有 20 年历史!
Pub Date : 2024-04-01 DOI: 10.1089/rej.2024.29011.editorial
Aubrey de Grey, Irina Conboy
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引用次数: 0
The Association Between Multidimensional Frailty and Poor Venous Accesses in a Geriatric Population: A Retrospective Study. 老年群体多维度虚弱与静脉通路不畅之间的关联:一项回顾性研究。
Pub Date : 2024-04-01 DOI: 10.1089/rej.2023.0054
Davide Mariani, Francesco Saverio Ragusa, Martina Alongi, Elisabetta Gugliuzza, Giorgia Petta, Alessandra Luca, Giuseppe Bianco, Anna Maria Marfisi, Diego Lalicata, Antonio Cambiano, Alessandro D'Aleo, Francesca Tantillo, Elisabetta Vaccaro, Nicola Veronese, Mario Barbagallo

Since the association between frailty and difficulty in finding venous access (VA) is largely unexplored and unclear in geriatrics, the aim of this study is to demonstrate how multidimensional frailty is associated with bad VA in a population of older hospitalized people. Multidimensional Prognostic Index (MPI), based on eight different domains usually assessed in comprehensive geriatric assessment, was used for identifying multidimensional frailty; VA heritage was investigated using a questionnaire prepared by a trained nurse, based on clinical experience. Overall, 145 patients were included (mean age 78.6 ± 7.6; males 51.0%). Frailer people, identified as an MPI >0.66 (MPI 3), had a significantly higher presence of bad VA (49.0% vs. 27.3% in MPI 3 and MPI 1 groups, p = 0.045), no success at first attempt (49.0% vs. 22.7% in MPI 3 and MPI 1 groups, p = 0.03), reported more frequently pain during VA attempts (63.3% in MPI 3 vs. 27.3 in MPI 1, p = 0.002), and significantly higher scores in the Numeric Rating Scale compared to their robust counterparts. Taking robust participants in MPI 1 as reference, after adjusting for potential confounders, frailer people (MPI 3) were at increased odds of bad VA (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 1.16-6.41; p = 0.02), not success at first attempt (OR = 3.67; 95% CI: 1.09-12.57; p = 0.04), and presence of pain during VA attempt (OR = 4.26; 95% CI: 1.30-13.92; p = 0.02). In conclusion, our study demonstrated an association between multidimensional frailty and bad VA in a population of older hospitalized people.

在老年病学领域,身体虚弱与寻找静脉通路(AV)困难之间的关系大多尚未得到探讨,也不明确,因此本研究旨在证明在老年住院患者中,身体虚弱与寻找静脉通路(AV)困难之间的关系。研究采用多维预后指数(MPI)来确定多维虚弱程度;由一名训练有素的护士根据临床经验编制问卷,对 AV 遗产进行调查。总共纳入了 145 名患者(平均年龄 78.6(±7.6)岁,男性占 51.0%)。与体格健壮的人相比,体格较弱的人存在不良反流的比例明显较高,首次尝试反流不成功,在尝试反流过程中更频繁地报告疼痛,NRS(数字评分量表)得分也明显较高,即使在调整了一些潜在的混杂因素后也是如此。总之,我们的研究表明,在住院老年人群中,多维度虚弱与不良房室术之间存在关联。
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引用次数: 0
Vitamin D Protects Against Cardiac Hypertrophy Through the Regulation of Mitochondrial Function in Aging Rats. 维生素 D 通过调节衰老大鼠的线粒体功能防止心肌肥大。
Pub Date : 2024-04-01 Epub Date: 2024-02-20 DOI: 10.1089/rej.2023.0061
Siamak Shahidi, Alireza Komaki, Iraj Salehi, Sara Soleimani Asl, Parisa Habibi, Fatemeh Ramezani-Aliakbari

Cardiac aging is defined as mitochondrial dysfunction of the heart. Vitamin D (VitD) is an effective agent in ameliorating cardiovascular disorders. In this study, we indicated the protective effects of VitD against cardiac aging. Male Wistar rats were randomly divided into four groups: control (CONT), D-galactose (D-GAL): aged rats induced by D-GAL, D-GAL + Ethanol: aged rats treated with ethanol, and D-GAL + VitD aged rats treated with VitD. Aging was induced by D-GAL at 150 mg/kg via intraperitoneal injection for 8 weeks. Aged rats were treated with VitD (D-GAL + VitD) by gavage for 8 weeks. The serum samples were used to evaluate biochemical factors, and heart tissues were assessed to determine oxidative stress and gene expression. The D-GAL rats exhibited cardiac hypertrophy, which was associated with decreased antioxidant enzyme activity, enhanced oxidative marker, and changes in the expression of mitochondrial genes in comparison with the control rats. Co-treatment with VitD ameliorated all these changes. In conclusion, VitD could protect the heart against D-GAL-induced aging via enhancing antioxidant effects, and the expression of mitochondrial genes.

心脏衰老是指心脏线粒体功能障碍。维生素 D(VitD)是改善心血管疾病的有效药物。在这项研究中,我们指出了维生素 D 对心脏衰老的保护作用。雄性 Wistar 大鼠被随机分为四组:对照组(CONT)、D-半乳糖组(D-GAL):由 D-半乳糖(D-GAL)诱导的衰老大鼠、D-GAL+乙醇组:用乙醇治疗的衰老大鼠,以及 D-GAL+ VitD 组:用 VitD 治疗的衰老大鼠。通过腹腔注射 150 毫克/千克的 D-GAL 诱导衰老,持续八周。给老年大鼠灌胃 VitD(D-GAL+ VitD)治疗八周。血清样本用于评估生化因子,心脏组织用于评估氧化应激和基因表达。与对照组大鼠相比,D-GAL 大鼠表现出心脏肥大,与抗氧化酶活性降低、氧化标记物增强和线粒体基因表达变化有关。与对照组大鼠相比,VitD 可改善所有这些变化。总之,VitD可通过增强抗氧化作用和线粒体基因的表达,保护心脏免受D-GAL诱导的衰老。
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引用次数: 0
Association Between the Length of Leukocyte Telomeres and Functional Performance of Older Adults: Observational Study. 白细胞端粒长度与老年人功能表现之间的关系:观察研究。
Pub Date : 2024-04-01 Epub Date: 2024-02-28 DOI: 10.1089/rej.2023.0050
Fabiana Souza Máximo Pereira, Ronaldo Luis Thomasini, Daniele Sirineu Pereira, Thyago José Silva, Cleyde Amaral Leite, Luís Guilherme Oliveira Reis, Vitor Amorim De Andrade Câmara, Matheus Brum Rodrigues da Costa, João Víctor Santos Bakir, Laise Santos Xavier, Leani Souza Máximo Pereira, Adriana Netto Parentoni, Ana Cristina Rodrigues Lacerda

Despite current literature pointing to a link between shortened telomeres and aging, chronic diseases, and geriatric syndromes, the precise implications of this connection remain unclear. The aim of this exploratory, cross-sectional, observational study was to investigate the association between the relative telomere length (RTL) of peripheral blood leukocyte subtypes (mononuclear cells and granulocytes) and physical performance using the Short Physical Performance Battery (SPPB) in older adults. A cohort of 95 participants was recruited, which included men and women aged over 60 years (70.48 ± 5.5 years). It was found that mononuclear cell RTL was significantly lower than that of granulocytes (p < 0.0001). Moreover, individuals with good SPPB performance exhibited lower mononuclear cell RTL compared with those with moderate or poor performance. However, no significant differences were observed in granulocyte RTL between different SPPB performance groups. The global SPPB score showed an inverse correlation with mononuclear cell RTL, but this correlation was not present with granulocyte RTL. Similarly, the SPPB sit-to-stand domain correlated with mononuclear cell RTL, but no such correlation was found with granulocyte RTL. Our findings challenge conventional expectations, suggesting that shorter mononuclear cell RTL may be associated with favorable functional capacity. The variations in RTL between mononuclear cells and granulocytes highlight their distinct biological roles and turnover rates. A history of immune responses may influence mononuclear cell RTL dynamics, while telomerase activity may protect granulocyte RTL from significant shortening. The unexpected associations observed in mononuclear cell RTL emphasize the complex interplay between immune responses, cellular aging, and functional capacity in older adults.

尽管目前有文献指出端粒缩短与衰老、慢性疾病和老年综合症之间存在联系,但这种联系的确切含义仍不清楚。在这项探索性、横断面、观察性研究中,我们的目的是利用短期体能测试(SPPB)调查老年人外周血白细胞亚型(单核细胞和粒细胞)的端粒相对长度(RTL)与体能表现之间的关系。我们招募了 95 名参与者,其中包括 60 岁以上的男性和女性(70.48 ± 5.5 岁)。我们发现,单核细胞的 RTL 明显低于粒细胞(P
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引用次数: 0
The Clinical Effects of Pharmacotherapy Combined with Blood Flow Restriction and Isometric Exercise Training in Rehabilitating Patients with Heart Failure with Reduced Ejection Fraction. 药物治疗结合血流限制和等长运动训练对射血分数降低型心力衰竭患者康复的临床效果。
Pub Date : 2024-02-01 DOI: 10.1089/rej.2023.0070
Pinxia Wu, Yu Liu

Heart failure with reduced ejection fraction (HFrEF) is associated with reduced cardiac function and impaired quality of life. Blood flow restriction (BFR) training is emerging as a potential adjunctive therapy. This study aimed at evaluating the efficacy of combination of BFR and isometric exercises on cardiac function, functional status, and quality of life in HFrEF patients. Totally 44 patients with HFrEF were equally divided into a control group and a combined treatment group. Both groups received standard pharmacotherapy and upper limb exercise, with the combined group also undergoing BFR and isometric exercise training. We assessed demographic and clinical characteristics, New York Heart Association (NYHA) functional classification, cardiac function parameters, serum Brain Natriuretic Peptide levels, physical capacity via the 6-minute walking test, and quality of life using the Heart Failure Questionnaire (Minnesota Living with Heart Failure Questionnaire). Post-treatment, the combined group significantly improved in NYHA classification (p = 0.012), with more patients shifting to a better class. Cardiac function improved in both groups, with the combined group showing a greater increase in mean left ventricular ejection fractions (p < 0.001), and reductions in left ventricular end-diastolic and end-systolic diameters (p < 0.05). The addition of BFR training to standard pharmacotherapy with upper limb exercise in HFrEF patients led to significant enhancements in cardiac function, functional status, and quality of life. These findings support the integration of BFR training into conventional HFrEF treatment regimens to maximize patient recovery outcomes.

射血分数降低型心力衰竭(HFrEF)与心功能减退和生活质量下降有关。血流限制(BFR)训练正成为一种潜在的辅助疗法。本研究旨在评估血流限制训练与等长运动相结合对射血分数不足型心力衰竭患者的心功能、功能状态和生活质量的影响。研究将 44 名高频低氧血症患者平均分为对照组和联合治疗组。两组患者均接受标准药物治疗和上肢运动,其中联合治疗组还接受了BFR和等长运动训练。我们评估了人口统计学和临床特征、纽约心脏协会(NYHA)功能分级、心功能参数、血清 BNP 水平、通过 6 分钟步行测试(6MWT)获得的体能以及使用心衰问卷(MLHFQ)获得的生活质量。治疗后,联合组患者的 NYHA 分级明显改善(p = 0.012),更多患者转入更好的级别。两组患者的心功能均有所改善,联合组患者的平均左心室射血分数(LVEF,p < 0.001)提高幅度更大,左心室舒张末期(LVEDd)和收缩末期(LVESd,p < 0.05)均有所下降。在对高频心衰患者进行上肢运动的标准药物治疗的基础上,再进行BFR训练,可显著提高患者的心功能、功能状态和生活质量。这些研究结果支持将 BFR 训练纳入传统的高频心衰治疗方案,以最大限度地提高患者的康复效果。
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引用次数: 0
Acknowledgment of Reviewers 2023. 鸣谢 2023 年审稿人。
Pub Date : 2024-02-01 Epub Date: 2023-12-18 DOI: 10.1089/rej.2023.29010.ack
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引用次数: 0
Melatonin Ameliorates Sevoflurane Anesthesia-Induced Deficits in Learning and Memory of Aged Mice Through Nrf2 Signaling Related Ferroptosis. 褪黑素通过与铁突变相关的Nrf2信号转导改善七氟醚麻醉引起的老年小鼠学习和记忆缺陷。
Pub Date : 2024-02-01 Epub Date: 2024-02-06 DOI: 10.1089/rej.2023.0051
Honghu Ni, Yijia Chen, Yongxiang Xie

Our research aimed at investigating the protective effects in aged mice exposed to sevoflurane anesthesia. To assess learning and memory abilities and exploratory behavior, the novel object recognition (NOR) test, Morris water maze (MWM) test, and open field test were employed. Commercial kits were used to measure levels of malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase activity, superoxide dismutase activity, catalase activity, and iron. The messenger RNA and protein levels of ferritin heavy chain 1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and glutathione peroxidase 4 in the hippocampus were detected. Treatment with melatonin significantly ameliorated the decrease in exploration time of novel objects and the discrimination index induced by sevoflurane anesthesia. Melatonin also reduced escape latencies and increased the time spent in the target quadrant in the MWM test. In the open field test, melatonin-treated mice exhibited greater exploratory activity, including longer distances traveled and a higher number of rearing events. Further, melatonin treatment markedly decreased the levels of oxidative stress markers and iron in the hippocampus of aged mice exposed to sevoflurane anesthesia. However, the beneficial effects of melatonin were significantly attenuated following treatment with the Nrf2 inhibitor ML385. Our results suggest that melatonin could alleviate learning and memory impairment induced by sevoflurane anesthesia in aged mice through its antioxidant properties, partially through the Nrf2 pathway.

我们的研究旨在探讨七氟醚麻醉对老年小鼠的保护作用。为了评估小鼠的学习记忆能力和探索行为,我们采用了新物体识别(NOR)测试、莫里斯水迷宫(MWM)测试和空地测试。商用试剂盒用于测量丙二醛、NADPH氧化酶活性、超氧化物歧化酶活性、过氧化氢酶活性和铁的水平。还检测了海马中铁蛋白重链 1、核因子红细胞 2 相关因子 2(Nrf2)、血红素加氧酶 1 和谷胱甘肽过氧化物酶 4 的 mRNA 和蛋白质水平。褪黑素能明显改善七氟醚麻醉引起的探索新物体时间和辨别指数的减少。在莫里斯水迷宫测试中,褪黑素还能减少逃逸潜伏期,增加在目标象限停留的时间。在开阔地测试中,褪黑激素处理的小鼠表现出更强的探索活动,包括更长的行进距离和更多的饲养活动。此外,褪黑素还能显著降低七氟醚麻醉下老年小鼠海马中氧化应激标记物和铁的水平。然而,褪黑素的有益作用在使用Nrf2抑制剂ML385处理后明显减弱。我们的研究结果表明,褪黑素可通过其抗氧化特性(部分通过Nrf2途径)减轻七氟醚麻醉对老年小鼠学习和记忆的损伤。
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引用次数: 0
Irreplaceable Judy Campisi. 无可替代的朱迪-坎皮西
Pub Date : 2024-02-01 DOI: 10.1089/rej.2024.0010
Irina Conboy
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引用次数: 0
Naringenin Orchestrates and Regulates the Reactive Oxygen Species-Mediated Pathways and Proinflammatory Signaling: Targeting Hallmarks of Aging-Associated Disorders. 柚皮苷协调和调节 ROS 介导的途径和促炎信号传导:针对衰老相关疾病的标志。
Pub Date : 2024-02-01 DOI: 10.1089/rej.2023.0065
Deepika, Tikam Chand Dakal, Narendra Kumar Sharma, Vipin Ranga, Pawan Kumar Maurya

The therapeutic application of flavonoids in the management of infectious diseases, cancers, chronic wounds, aging, and neurodegenerative disorders has been well documented in scientific literature. The citric flavonoid naringenin comes under the category of flavanone and exhibits a plethora of health benefits. Very few flavonoids such as curcumin, resveratrol, catechin, quercetin, and kaempferol have been studied to exert their anti-aging properties in humans. The effect of naringenin in the context of age-associated disorders in detail has not been elucidated yet. The databases used for the literature search were Science Direct, Google Scholar, and PubMed. More emphasis has been put on the recent literature on "naringenin" and its effect on "age-associated disorders." Almost all chronic degenerative disorders are characterized by oxidative stress and inflammatory response. The study aims at highlighting the reactive oxygen species-mediated activity of naringenin and the underlying molecular mechanism leading to the prevention of various age-associated disorders. Altogether, the review presents a systematic comprehension of the pharmaceutical and clinicopathological benefits of naringenin in age-associated disorders.

类黄酮在治疗传染病、癌症、慢性伤口、衰老和神经退行性疾病方面的应用已在科学文献中得到充分证明。柠檬黄酮类化合物柚皮苷属于黄烷酮类化合物,具有大量的健康益处。姜黄素、白藜芦醇、儿茶素、槲皮素和山柰酚等黄酮类化合物在人体中发挥抗衰老作用的研究很少。柚皮苷对老年相关疾病的影响尚未得到详细阐明。用于文献检索的数据库包括 Science Direct、Google Scholar 和 PubMed。最近关于 "柚皮素 "及其对 "老年相关疾病 "影响的文献受到了更多关注。几乎所有慢性退行性疾病都以氧化应激和炎症反应为特征。本研究旨在强调柚皮素介导的活性氧及其预防各种老年相关疾病的分子机制。总之,这篇综述系统地阐述了柚皮苷对老年相关疾病的药物和临床病理学益处。
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引用次数: 0
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Rejuvenation research
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