This study aims to investigate the expression differences of peripheral blood mononuclear cells (PBMCs) in patients with elderly rheumatoid arthritis (ERA). Differentially expressed genes (DEGs) of PBMCs between young patients with RA (RA_Y) and elderly patients with RA (RA_A) were identified by RNA sequencing using the DESeq2 package, followed by bioinformatics analysis. The overlapped targets of the current DEGs and proteomic differentially expressed proteins (another set of unpublished data) were identified and further validated. The bioinformatics analysis revealed significant transcriptomic heterogeneity between RA_A and RA_Y. A total of 348 upregulated and 363 downregulated DEGs were identified. Gene functional enrichment analysis indicated that the DEGs, which represented senescence phenotype for patients with ERA, were enriched in pathways such as Phosphatidylinositol3 kinase/AKT serine-threonine protein kinase (PI3K/Akt) signaling, Mitogen-activated protein kinases (MAPK) signaling, toll-like receptor family, neutrophil degranulation, and immune-related pathways. Gene set enrichment analysis further confirmed the activation of humoral immune response pathways in RA_A. Quantitative polymerase chain reaction validated the expression of five representative DEGs such as SPTA1, SPTB, VNN1, TNXB, and KRT1 in PBMCs of patients with ERA. Patients with ERA have significant senescence phenotype differences versus the young patients. The DEGs identified may facilitate exploring the biomarkers of senescence in RA.
{"title":"Secretory Phenotype in Peripheral Blood Mononuclear Cells of Elderly Patients with Rheumatoid Arthritis.","authors":"Wenlong Wang, Yanjuan Chen, Yidi Shen, Jian Chen, Xiaoyang Yao, Yongjun Cheng, Jinzhong Xu, Lisha Ma, Yong Chen, Chuanfu Zhang","doi":"10.1089/rej.2024.0008","DOIUrl":"10.1089/rej.2024.0008","url":null,"abstract":"<p><p>This study aims to investigate the expression differences of peripheral blood mononuclear cells (PBMCs) in patients with elderly rheumatoid arthritis (ERA). Differentially expressed genes (DEGs) of PBMCs between young patients with RA (RA_Y) and elderly patients with RA (RA_A) were identified by RNA sequencing using the <i>DESeq2</i> package, followed by bioinformatics analysis. The overlapped targets of the current DEGs and proteomic differentially expressed proteins (another set of unpublished data) were identified and further validated. The bioinformatics analysis revealed significant transcriptomic heterogeneity between RA_A and RA_Y. A total of 348 upregulated and 363 downregulated DEGs were identified. Gene functional enrichment analysis indicated that the DEGs, which represented senescence phenotype for patients with ERA, were enriched in pathways such as Phosphatidylinositol3 kinase/AKT serine-threonine protein kinase (PI3K/Akt) signaling, Mitogen-activated protein kinases (MAPK) signaling, toll-like receptor family, neutrophil degranulation, and immune-related pathways. Gene set enrichment analysis further confirmed the activation of humoral immune response pathways in RA_A. Quantitative polymerase chain reaction validated the expression of five representative DEGs such as <i>SPTA1</i>, <i>SPTB</i>, <i>VNN1</i>, <i>TNXB</i>, and <i>KRT1</i> in PBMCs of patients with ERA. Patients with ERA have significant senescence phenotype differences versus the young patients. The DEGs identified may facilitate exploring the biomarkers of senescence in RA.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"122-130"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-05-13DOI: 10.1089/rej.2024.0014
Xia Li, Liang Chen, Yunyun Sun, Yuanhai Li
Total hip arthroplasty (THA) is a highly effective intervention for addressing hip joint issues, yet managing perioperative pain remains a significant challenge. In this study, we aimed to investigate the impact of supplementing ropivacaine with dexmedetomidine in ultrasound-guided continuous pericapsular nerve group block (PENGB) among elderly patients undergoing THA. We conducted a retrospective analysis involving 112 elderly patients who underwent THA. These patients were divided into two groups: the Control group, receiving ropivacaine alone, and the DEX group, receiving ropivacaine combined with dexmedetomidine. We evaluated various parameters including hemodynamic data, postoperative pain levels assessed using the Visual Analog Scale, cognitive status measured with the Montreal Cognitive Assessment, and serum markers (S100β and GFAP). Our findings revealed that the DEX group exhibited improved stability in blood pressure and oxygen saturation following surgery. Moreover, patients in the DEX group reported significantly lower levels of pain at 6 and 12 hours postsurgery, with a prolonged duration of pain relief. Furthermore, dexmedetomidine administration was associated with preserved cognitive function during the early postoperative period. Analysis of serum markers suggested potential cognitive protection conferred by the addition of dexmedetomidine. Overall, our study underscores the multifaceted benefits of incorporating dexmedetomidine into ropivacaine-based PENGB for elderly THA patients.
{"title":"Effects of Dexmedetomidine Added to Ropivacaine in Ultrasound-Guided Continuous Pericapsular Nerve Group Block Among Elderly Patients Undergoing Total Hip Arthroplasty.","authors":"Xia Li, Liang Chen, Yunyun Sun, Yuanhai Li","doi":"10.1089/rej.2024.0014","DOIUrl":"10.1089/rej.2024.0014","url":null,"abstract":"<p><p>Total hip arthroplasty (THA) is a highly effective intervention for addressing hip joint issues, yet managing perioperative pain remains a significant challenge. In this study, we aimed to investigate the impact of supplementing ropivacaine with dexmedetomidine in ultrasound-guided continuous pericapsular nerve group block (PENGB) among elderly patients undergoing THA. We conducted a retrospective analysis involving 112 elderly patients who underwent THA. These patients were divided into two groups: the Control group, receiving ropivacaine alone, and the DEX group, receiving ropivacaine combined with dexmedetomidine. We evaluated various parameters including hemodynamic data, postoperative pain levels assessed using the Visual Analog Scale, cognitive status measured with the Montreal Cognitive Assessment, and serum markers (S100β and GFAP). Our findings revealed that the DEX group exhibited improved stability in blood pressure and oxygen saturation following surgery. Moreover, patients in the DEX group reported significantly lower levels of pain at 6 and 12 hours postsurgery, with a prolonged duration of pain relief. Furthermore, dexmedetomidine administration was associated with preserved cognitive function during the early postoperative period. Analysis of serum markers suggested potential cognitive protection conferred by the addition of dexmedetomidine. Overall, our study underscores the multifaceted benefits of incorporating dexmedetomidine into ropivacaine-based PENGB for elderly THA patients.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"115-121"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxidative stress (OS) causes biochemical and morphological alterations in erythrocytes. The primary factors contributing to OS are aging and storage. Antioxidants significantly alleviate OS. Therefore, this study aimed to investigate the response of young and old erythrocytes to vitamin C and vitamin E during storage. Erythrocytes were separated into young and old by the Percoll method. Each erythrocyte subpopulation was categorized into the i) Control (additive solution-7 [AS-7]) and ii) vitamin C and vitamin E in AS-7 (VC+VE) groups and stored for 21 days at 4°C. OS, antioxidant, and aging markers were analyzed on days 1, 14, and 21. The activity of antioxidant enzymes was similar throughout storage in young cells. However, superoxide dismutase activity elevated in old cells (Control and VC+VE) on days 1 and 21. Catalase (CAT) activity increased on days 14 and 21, whereas glutathione peroxidase (GPX) increased on days 1 and 14 in old Controls. However, in old VC+VE, CAT increased on day 21 and GPX increased on day 1. Advanced oxidation protein products, superoxides, glutathione, and uric acid increased in old cells throughout storage. Malondialdehyde decreased in old VC+VE compared with old Control on days 14 and 21. Sialic acids and glutamate oxaloacetate transaminase activity were higher in young cells compared to old cells. Young cells exhibited lower oxidative changes throughout storage. Vitamin C and vitamin E were effective in maintaining the redox balance in old cells. These findings emphasize the need for specific approaches for different subpopulations during erythrocyte banking.
{"title":"Differential Responses of Young and Old Erythrocytes Stored with Vitamin C and Vitamin E in Additive Solution-7.","authors":"Masannagari Pallavi, Vani Rajashekaraiah","doi":"10.1089/rej.2024.0033","DOIUrl":"10.1089/rej.2024.0033","url":null,"abstract":"<p><p>Oxidative stress (OS) causes biochemical and morphological alterations in erythrocytes. The primary factors contributing to OS are aging and storage. Antioxidants significantly alleviate OS. Therefore, this study aimed to investigate the response of young and old erythrocytes to vitamin C and vitamin E during storage. Erythrocytes were separated into young and old by the Percoll method. Each erythrocyte subpopulation was categorized into the i) Control (additive solution-7 [AS-7]) and ii) vitamin C and vitamin E in AS-7 (VC+VE) groups and stored for 21 days at 4°C. OS, antioxidant, and aging markers were analyzed on days 1, 14, and 21. The activity of antioxidant enzymes was similar throughout storage in young cells. However, superoxide dismutase activity elevated in old cells (Control and VC+VE) on days 1 and 21. Catalase (CAT) activity increased on days 14 and 21, whereas glutathione peroxidase (GPX) increased on days 1 and 14 in old Controls. However, in old VC+VE, CAT increased on day 21 and GPX increased on day 1. Advanced oxidation protein products, superoxides, glutathione, and uric acid increased in old cells throughout storage. Malondialdehyde decreased in old VC+VE compared with old Control on days 14 and 21. Sialic acids and glutamate oxaloacetate transaminase activity were higher in young cells compared to old cells. Young cells exhibited lower oxidative changes throughout storage. Vitamin C and vitamin E were effective in maintaining the redox balance in old cells. These findings emphasize the need for specific approaches for different subpopulations during erythrocyte banking.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-04-09DOI: 10.1089/rej.2023.0071
Ling Wang
Sudden deafness poses a significant threat to patients' quality of life, yet effective indicators for evaluating its onset and prognosis remain elusive. The inner ear is primarily supplied by the labyrinthine artery, which lacks collateral circulation. Changes in coagulation function and hemorheology can cause spasm or thrombosis of the labyrinthine artery, leading to ischemia, hypoxia, and microcirculation disorders in the inner ear, ultimately resulting in sudden deafness. This retrospective study examined 196 patients with sudden deafness, utilizing the 2015 Chinese guideline for diagnosis and treatment classification. Coagulation system analysis used the STA-R Evolution automatic coagulation analyzer, measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen (FIB). Plasma lactate concentration was determined using a Johnson and Johnson Fusion 5.1 model plasma lactate detector. Results of the study revealed a correlation between the degree of hearing loss and disease prognosis. Patients with higher grade hearing loss exhibited elevated plasma lactate levels upon admission compared with those with lower grade hearing loss. Importantly, elevated plasma lactate levels at admission served as predictive indicators for treatment outcomes. In addition, patients with ineffective treatment demonstrated a more coagulable blood state, as evidenced by the lower APTT (ineffective treatment: 31.47 ± 4.55 seconds, effective treatment: 35.17 ± 5.38 seconds) and PT on admission, but higher plasma FIB. In conclusion, plasma lactate levels upon admission hold promise as prognostic markers for sudden deafness treatment outcomes, providing valuable insights for clinical management.
{"title":"Clinical Relevance of Plasma Lactic Acid in the Onset and Prognosis of Sudden Deafness.","authors":"Ling Wang","doi":"10.1089/rej.2023.0071","DOIUrl":"10.1089/rej.2023.0071","url":null,"abstract":"<p><p>Sudden deafness poses a significant threat to patients' quality of life, yet effective indicators for evaluating its onset and prognosis remain elusive. The inner ear is primarily supplied by the labyrinthine artery, which lacks collateral circulation. Changes in coagulation function and hemorheology can cause spasm or thrombosis of the labyrinthine artery, leading to ischemia, hypoxia, and microcirculation disorders in the inner ear, ultimately resulting in sudden deafness. This retrospective study examined 196 patients with sudden deafness, utilizing the 2015 Chinese guideline for diagnosis and treatment classification. Coagulation system analysis used the STA-R Evolution automatic coagulation analyzer, measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen (FIB). Plasma lactate concentration was determined using a Johnson and Johnson Fusion 5.1 model plasma lactate detector. Results of the study revealed a correlation between the degree of hearing loss and disease prognosis. Patients with higher grade hearing loss exhibited elevated plasma lactate levels upon admission compared with those with lower grade hearing loss. Importantly, elevated plasma lactate levels at admission served as predictive indicators for treatment outcomes. In addition, patients with ineffective treatment demonstrated a more coagulable blood state, as evidenced by the lower APTT (ineffective treatment: 31.47 ± 4.55 seconds, effective treatment: 35.17 ± 5.38 seconds) and PT on admission, but higher plasma FIB. In conclusion, plasma lactate levels upon admission hold promise as prognostic markers for sudden deafness treatment outcomes, providing valuable insights for clinical management.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"81-86"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-04-24DOI: 10.1089/rej.2023.0069
Bomi Lee, Myeong-Sang Yu, Jae Gwang Song, Hyang-Mi Lee, Hyung Wook Kim, Dokyun Na
Recently, natural herbs have gained increasing attention owing to their comparatively low toxicity levels and the abundance of historical medical documentation regarding their use. Nevertheless, owing to a lack of knowledge regarding these herbs and their compounds, attempts to find those that could be beneficial for treating diseases have often been ad hoc; thus, there is now a growing demand for an in silico method to identify beneficial herbs. In this study, we present a computational approach for identifying natural herbs specifically effective in treating cognitive decline in Alzheimer's disease (AD) sufferers, which analyzes the similarities between herbal compounds and known drugs targeting AD-related proteins. Our in silico method suggests that Corydalis ternata can improve cognitive decline in AD sufferers. Behavioral tests with an AD mouse model for the confirmation of the in silico prediction reveals that C. ternata significantly alleviated the cognitive decline (memory and motor functions) caused by neurodegeneration. Further pathology analyses reveal that C. ternata decreases the level of Aβ plaques, reduces neuroinflammation, and promotes autophagy flux, and thus C. ternata can be clinically effective for preventing mild cognitive impairment during the early stages of AD. These findings highlight the potential utility of our in silico method and the potential clinical application of the identified natural herb in treating and preventing AD.
近来,天然草药因其相对较低的毒性水平和大量有关其用途的历史医学文献而受到越来越多的关注。然而,由于缺乏对这些草药及其化合物的了解,寻找有益于治疗疾病的草药的尝试往往是临时性的;因此,现在人们越来越需要一种硅学方法来识别有益的草药。在这项研究中,我们提出了一种计算方法,通过分析草药化合物与已知的针对注意力缺失症相关蛋白的药物之间的相似性,来确定对治疗注意力缺失症患者认知能力下降特别有效的天然草药。我们的硅学方法表明,C. ternata能改善AD患者的认知能力衰退。为了证实我们的硅学预测,我们用一种注意力缺失症小鼠模型进行了行为测试,结果表明 C. ternata 能明显缓解神经变性引起的认知能力下降(记忆和运动功能)。进一步的病理分析表明,蛇床子素能降低Aβ斑块的水平,减少神经炎症,促进自噬通量,因此蛇床子素在临床上可有效预防AD早期阶段的轻度认知障碍。这些发现凸显了我们的硅学方法的潜在效用,以及所发现的天然草药在治疗和预防AD方面的潜在临床应用。
{"title":"<i>Corydalis ternata</i> Nakai Alleviates Cognitive Decline in Alzheimer's Disease by Reducing β-Amyloid and Neuroinflammation.","authors":"Bomi Lee, Myeong-Sang Yu, Jae Gwang Song, Hyang-Mi Lee, Hyung Wook Kim, Dokyun Na","doi":"10.1089/rej.2023.0069","DOIUrl":"10.1089/rej.2023.0069","url":null,"abstract":"<p><p>Recently, natural herbs have gained increasing attention owing to their comparatively low toxicity levels and the abundance of historical medical documentation regarding their use. Nevertheless, owing to a lack of knowledge regarding these herbs and their compounds, attempts to find those that could be beneficial for treating diseases have often been <i>ad hoc</i>; thus, there is now a growing demand for an <i>in silico</i> method to identify beneficial herbs. In this study, we present a computational approach for identifying natural herbs specifically effective in treating cognitive decline in Alzheimer's disease (AD) sufferers, which analyzes the similarities between herbal compounds and known drugs targeting AD-related proteins. Our <i>in silico</i> method suggests that <i>Corydalis ternata</i> can improve cognitive decline in AD sufferers. Behavioral tests with an AD mouse model for the confirmation of the <i>in silico</i> prediction reveals that <i>C. ternata</i> significantly alleviated the cognitive decline (memory and motor functions) caused by neurodegeneration. Further pathology analyses reveal that <i>C. ternata</i> decreases the level of Aβ plaques, reduces neuroinflammation, and promotes autophagy flux, and thus <i>C. ternata</i> can be clinically effective for preventing mild cognitive impairment during the early stages of AD. These findings highlight the potential utility of our <i>in silico</i> method and the potential clinical application of the identified natural herb in treating and preventing AD.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"87-101"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether Aprepitant, a substance P receptor blocker, could be utilized to alleviate post-stroke pneumonia is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 h, 48 h, and 72 h post-stroke. On the other hand, different concentrations of aprepitant (0.5, 1, 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-h post-stroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate post-stroke pneumonia in mice suggesting its potential therapeutic use in the clinic.
物质 P 升高可用于预测脑梗塞第一周的早期死亡率。本研究探讨了是否可以利用物质 P 受体阻断剂阿普瑞坦来缓解卒中后肺炎。本研究以 C57BL/6J 雄性小鼠为对象,构建了大脑中动脉闭塞(MCAO)的腔内单丝模型,并检测了卒中后 24 h、48 h 和 72 h 采集的支气管肺泡灌洗液(BALF)和肺组织匀浆中 P 物质的相对表达。另一方面,将不同浓度的阿普瑞坦(0.5、1、2 毫克/千克)雾化并吸入 MCAO 小鼠体内。中风后72小时,在收集的BALF和肺组织匀浆中检测到炎症细胞因子和细菌负荷,组织学检查显示肺损伤。服用阿瑞匹坦可减少 BALF 中的总蛋白、总细胞、中性粒细胞和巨噬细胞。阿瑞匹坦还能降低肺组织匀浆中白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α、干扰素γ、单核细胞趋化蛋白-1和IL-10的浓度。总之,阿瑞匹坦可减轻小鼠卒中后肺炎,这表明它有可能用于临床治疗。
{"title":"Aprepitant alleviates post-stroke pneumonia in a mouse model of middle cerebral artery occlusion.","authors":"Zhihui Xie, Minghui Xin, Fatao Yu, Xiaolin Zhu","doi":"10.1089/rej.2024.0011","DOIUrl":"https://doi.org/10.1089/rej.2024.0011","url":null,"abstract":"Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether Aprepitant, a substance P receptor blocker, could be utilized to alleviate post-stroke pneumonia is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 h, 48 h, and 72 h post-stroke. On the other hand, different concentrations of aprepitant (0.5, 1, 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-h post-stroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate post-stroke pneumonia in mice suggesting its potential therapeutic use in the clinic.","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":"1 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper presents the concept of Antagonistic Pathogenic Pleiotropy (APaP), in which an abnormality that causes a specific pathology can simultaneously reduce other morbidities through unrelated mechanisms, resulting in the pathology causing less morbidity or mortality than expected. The concept is illustrated by the case of Essential Thrombocythaemia (ET). ET patients have substantially elevated platelets, and are therefore expected to have increased thrombotic events leading to reduced life expectancy. However ET patients do not have reduced life expectancy. A possible explanation is that elevated platelets produce higher levels of Platelet Factor 4 (PF4), which has been found to reduce age-associated decline in immune and cognitive function in mice, and has been suggested as a treatment for age-associated illness. The benefit of elevated PF4 is hypothesised to balance the increased morbidity from hematological causes. Searches for other indications where a well-defined pathology is not associated with concomitant reduction in overall mortality may be a route to identifying factors that could protect against, prevent or treat chronic disease.
{"title":"Platelet Factor 4 and longevity of patients with essential thromobocythaemia: an example of Antagonistic Pathogenic Pleiotropy (APaP).","authors":"William Bains","doi":"10.1089/rej.2023.0066","DOIUrl":"https://doi.org/10.1089/rej.2023.0066","url":null,"abstract":"This paper presents the concept of Antagonistic Pathogenic Pleiotropy (APaP), in which an abnormality that causes a specific pathology can simultaneously reduce other morbidities through unrelated mechanisms, resulting in the pathology causing less morbidity or mortality than expected. The concept is illustrated by the case of Essential Thrombocythaemia (ET). ET patients have substantially elevated platelets, and are therefore expected to have increased thrombotic events leading to reduced life expectancy. However ET patients do not have reduced life expectancy. A possible explanation is that elevated platelets produce higher levels of Platelet Factor 4 (PF4), which has been found to reduce age-associated decline in immune and cognitive function in mice, and has been suggested as a treatment for age-associated illness. The benefit of elevated PF4 is hypothesised to balance the increased morbidity from hematological causes. Searches for other indications where a well-defined pathology is not associated with concomitant reduction in overall mortality may be a route to identifying factors that could protect against, prevent or treat chronic disease.","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":"34 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140735512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Pharmacodynamics and Mechanism of Astragali Radix and Anemarrhenae Rhizoma in Treating Chronic Heart Failure by Inhibiting Complement Activation.","authors":"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","doi":"10.1089/rej.2023.0068","DOIUrl":"10.1089/rej.2023.0068","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"61-74"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1089/rej.2024.29011.editorial
Aubrey de Grey, Irina Conboy
{"title":"Rejuvenation Research Is 20 Years Old!","authors":"Aubrey de Grey, Irina Conboy","doi":"10.1089/rej.2024.29011.editorial","DOIUrl":"https://doi.org/10.1089/rej.2024.29011.editorial","url":null,"abstract":"","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":"80 1","pages":"43"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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。
{"title":"The Association Between Multidimensional Frailty and Poor Venous Accesses in a Geriatric Population: A Retrospective Study.","authors":"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","doi":"10.1089/rej.2023.0054","DOIUrl":"10.1089/rej.2023.0054","url":null,"abstract":"<p><p>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, <i>p</i> = 0.045), no success at first attempt (49.0% vs. 22.7% in MPI 3 and MPI 1 groups, <i>p</i> = 0.03), reported more frequently pain during VA attempts (63.3% in MPI 3 vs. 27.3 in MPI 1, <i>p</i> = 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; <i>p</i> = 0.02), not success at first attempt (OR = 3.67; 95% CI: 1.09-12.57; <i>p</i> = 0.04), and presence of pain during VA attempt (OR = 4.26; 95% CI: 1.30-13.92; <i>p</i> = 0.02). In conclusion, our study demonstrated an association between multidimensional frailty and bad VA in a population of older hospitalized people.</p>","PeriodicalId":94189,"journal":{"name":"Rejuvenation research","volume":" ","pages":"75-80"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}