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Biomedicine & Pharmacotherapy =... Jun 2024Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell...
Idiopathic pulmonary fibrosis is an aging-related, chronic lung disease, with unclear pathogenesis and no effective treatment. One of the triggering factors in cell aging is oxidative stress and it is known to have a role in idiopathic pulmonary fibrosis. In this paper, the protective effect of the E-CG-01 (3,4-lacto-cycloastragenol) molecule in terms of its antioxidant properties was evaluated in the bleomycin induced mice lung fibrosis model. Bleomycin sulfate was administered as a single dose (2.5 U/kg body weight) intratracheally to induce lung fibrosis. E-CG-01 was administered intraperitoneally in three different doses (2 mg/kg/day, 6 mg/kg/day, and 10 mg/kg/day) for 14 days, starting three days before the bleomycin administration. Fibrosis was examined by Hematoxylin-Eosin, Masson Trichrome, and immunohistochemical staining for TGF-beta1, Type I collagen Ki-67, and gama-H2AX markers. Activity analysis of catalase and Superoxide dismutase enzymes, measurement of total oxidant, total glutathione, and Malondialdehyde levels. In histological analysis, it was determined that all three different doses of the molecule provided a prophylactic effect against the progression of fibrosis compared to the bleomycin control group. However, it was observed that only the molecule applied in the high dose decreased the total oxidant stress level. Lung weight ratio increased in the BLM group but significantly reduced with high-dose E-CG-01. E-CG-01 at all doses reduced collagen deposition, TGF-β expression, and Ki-67 expression compared to the BLM group. Intermediate and high doses of E-CG-01 also significantly reduced alveolar wall thickness and edema formation. These findings suggest that E-CG-01 has potential therapeutic effects in mitigating lung fibrosis through its antioxidant properties.
PubMed: 38943992
DOI: 10.1016/j.biopha.2024.117016 -
The Journal of Nutrition, Health & Aging Jun 2024Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment... (Review)
Review
BACKGROUND
Ketogenic diets (KD) have shown remarkable effects in many disease areas. It has been demonstrated in numerous animal experiments that KD is effective in the treatment of Alzheimer's disease (AD). But the clinical effect of treating AD is uncertain.
OBJECTIVE
To systematically review the impact of KD on cognitive function in AD.
METHODS
We conducted a search of three international databases-PubMed, Cochrane Library, and Embase-to retrieve RCTs on the KD intervention for AD from the inception of the databases through October 2023. Two reviewers searched and screened the literature, extracted and checked relevant data independently, and assessed the risk of bias of the included studies. The meta-analysis was carried out utilizing RevMan 5.3 software.
RESULTS
A total of 10 RCTS involving 691 patients with AD were included. There were 357 participants in the intervention group and 334 participants in the control group. The duration of the KD intervention ranged from a minimum of 3 months to a maximum of 15 months. Meta-analysis results showed that KD could effectively improve the mental state of the elderly (NM scale) [MD = 7.56, 95%CI (3.02, 12.10), P = 0.001], MMSE [MD = 1.25, 95%CI (0.46, 2.04), P = 0.002], and ADAS-Cog [MD = -3.43, 95%CI (-5.98, -0.88), P = 0.008]. The elevation of ketone body (β-hydroxybutyric) [MD = 118.84, 95%CI (15.20, 222.48), P = 0.02] may also lead to the elevation of triglyceride [MD = 0.19, 95%CI (0.03, 0.35), P = 0.02] and low density lipoprotein [MD = 0.31, 95%CI (0.04, 0.58), P = 0.02].
CONCLUSION
Research conducted has indicated that the KD can enhance the mental state and cognitive function of those with AD, albeit potentially leading to an elevation in blood lipid levels. In summary, the good intervention effect and safety of KD are worthy of promotion and application in clinical treatment of AD.
PubMed: 38943982
DOI: 10.1016/j.jnha.2024.100306 -
The Journal of Nutrition, Health & Aging Jun 2024Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study...
OBJECTIVES
Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs.
METHODS
A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC.
RESULTS
Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]).
CONCLUSIONS
Intervention for improving medication non-adherence among older adults with NCDs should consider IC.
PubMed: 38943981
DOI: 10.1016/j.jnha.2024.100303 -
International Immunopharmacology Jun 2024As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions...
As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice. We replaced primed microglia with newly repopulated microglia through pharmacological administration and withdrawal of the colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397. Further, we performed a series of behavioral tests and flow cytometry in mouse models of middle cerebral artery occlusion (MCAO) to study the effects of microglial replacement on ischemic injury in the aged brain. With depletion and subsequent repopulation of microglia in MCAO mice, microglial replacement in aged mice improved neurological function and decreased brain infarction. This protective effect was accompanied by the reduction of peripheral immune cells infiltrating into brains. We showed that the repopulated microglia expressed elevated neuroprotective factors (including Cluster of Differentiation 206, transforming growth factor-β, and interleukin-10) and diminished expression of inflammatory markers (including Cluster of Differentiation 86, interleukin-6, and tumor necrosis factor α). Moreover, microglial replacement protected the blood-brain barrier and relieved neuronal death in aged mice subjected to 60 min of MCAO. These results imply that the replacement of microglia in the aged brain may alleviate brain damage and neuroinflammation, and therefore, ischemic brain damage. Thus, targeting microglia could be a promising therapeutic strategy for ischemic stroke.
PubMed: 38943977
DOI: 10.1016/j.intimp.2024.112473 -
International Immunopharmacology Jun 2024Idiopathic pulmonary fibrosis (IPF) is considered to be associated with aging. Both ER stress and the unfolded protein response (UPR) have been associated with pulmonary...
Idiopathic pulmonary fibrosis (IPF) is considered to be associated with aging. Both ER stress and the unfolded protein response (UPR) have been associated with pulmonary fibrosis via key mechanisms including AEC apoptosis, EMT, altered myofibroblast differentiation, and M2 macrophage polarization. A relationship between ER stress and aging has also been demonstrated in vitro, with increased p16 and p21 levels seen in lung epithelial cells of older IPF patients. The mechanism underlying ER stress regulation of IPF fibroblasts is still unclear. In this study, we aimed to delineate ER stress regulation in IPF-derived fibroblasts. Here, we found that ER stress markers (p-eIF2α, p-IREα, ATF6) and fibrosis markers (α-SMA and Collagen-I) were significantly increased in lung tissues of IPF patients and bleomycin-induced mouse models. Notably, the expression of PGC-1α was decreased in fibroblasts. In vivo experiments were designed using an AAV-6 vector mediated conditional PGC-1α knockout driven by a specific α-SMA promoter. Ablation of PGC-1α expression in fibroblasts promoted ER stress and supported the development of pulmonary fibrosis in a bleomycin-induced mouse model. In another experimental group, mice with conditional knockout of PGC-1α in fibroblasts and injected intraperitoneally with 4-PBA (an endoplasmic reticulum stress inhibitor) were protected from lung fibrosis. We further constructed an AAV-6 vector mediated PGC-1α overexpression model driven by a specific Collagen-I promoter. Overexpression of PGC-1α in fibroblasts suppressed ER stress and attenuated development of pulmonary fibrosis in bleomycin-induced mouse models. Taken together, this study identified PGC-1α as a promising target for developing novel therapeutic options for the treatment of lung fibrosis.
PubMed: 38943974
DOI: 10.1016/j.intimp.2024.112514 -
Journal of Clinical Neuroscience :... Jun 2024Sarcopenia has been purported to be a pre-operative risk factor that affects patient outcomes in oncological surgery, but no study as of yet has investigated the effect...
BACKGROUND
Sarcopenia has been purported to be a pre-operative risk factor that affects patient outcomes in oncological surgery, but no study as of yet has investigated the effect of sarcopenia in patients with spinal tumours. Psoas muscle measurements, including the psoas muscle index (PMI), are an objective way to determine sarcopenia.
OBJECTIVES
We investigated if PMI could predict post-operative outcomes (length of hospital stay and post-operative complications) in surgically treated spinal tumour patients in a multi-ethnic Asian population.
METHODS
We conducted a retrospective cohort study of patients with spinal tumours who underwent surgery at our tertiary institution from January 2016 to January 2020. PMI was measured on T2-weighted MRI sequences, at the middle of the L3 vertebral body and measurements were collected by 2 independent raters. The primary outcome was length of hospital stay (LOS), and the secondary outcome was post-operative complications. ROC curve was used to attain the cut-off value for PMI and the population was then stratified into 2 groups; sarcopenic if PMI was less than 1.22 and non-sarcopenic if the PMI value was more than or equal to 1.22. Multivariable linear regression was used for LOS, while multivariate logistic regression was used for complications.
RESULTS
57 patients were included with a mean length of stay of 17.8 days (SD 25.1) and the total number of patients with complications were 20 (35.1 %). Mean LOS was significantly higher in the sarcopenic group compared to the non-sarcopenic group. Univariate analysis confirmed the association of lower psoas muscle index corresponding with longer lengths of stay and this was corroborated in a multivariable linear regression model. There were no significant associations between PMI and postoperative complications.
CONCLUSIONS
Lower PMI values were significantly associated with a longer LOS. PMI may be warranted for risk stratifying Asian spinal tumour patients undergoing surgery.
PubMed: 38943906
DOI: 10.1016/j.jocn.2024.06.022 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024Citation scores (CS) have been traditionally used to measure the impact of scientific publications. Sourced from the Internet, Altmetric Attention Scores (AAS) are...
BACKGROUND AND AIMS
Citation scores (CS) have been traditionally used to measure the impact of scientific publications. Sourced from the Internet, Altmetric Attention Scores (AAS) are complementary metrics that assess how often publications are discussed and used globally. We compared by rank the top 500 papers by CS and AAS published in Clinical Nutrition with corresponding AAS and CS.
METHODS
A search for all publications in Clinical Nutrition was performed on Dimensions (https://app.dimensions.ai/discover/publication) on 3rd April 2024. Outputs were ranked according to CS and then by AAS with the top 500 in each category selected. Scores, year and type of publication were recorded. Correlation was expressed as the Spearman's rank coefficient (ϱ).
RESULTS
We identified 18,790 outputs. Within the top 500 publications ranked by CS, there was a significant weak positive correlation (ϱ = 0.235, P < 0.0001) between CS [median (IQR) 149 (116-223)] and AAS [7 (3-22)]. Ranked by AAS, there was a non-significant very weak positive correlation (ϱ = 0.072, P = 0.106) between AAS [55.5 (36-115)] and CS [42 (16.5-94.5)]. Trends remained similar when grouped by publication type. Guidelines, ranked by CS, had the highest CS and ranked by AAS, the highest CS and AAS. Publications per year, by year, ranked by CS, had a negatively skewed distribution peaking in 2012 and declined thereafter, but when ranked by AAS, had a moderately positive linear trend from 2001 to 2024 (ϱ = 0.513, P < 0.0001).
CONCLUSION
Correlation between CS and AAS was weak. Guidelines had the highest CS and AAS. CS are iterative taking years to mature while AAS are immediate.
PubMed: 38943805
DOI: 10.1016/j.clnu.2024.06.021 -
Maturitas Jun 2024A helpful method to understand cognitive decline in older people is to consider this entity as increasing cognitive frailty caused by a number of interacting... (Review)
Review
A helpful method to understand cognitive decline in older people is to consider this entity as increasing cognitive frailty caused by a number of interacting pathological processes. Over the last 20 years, multiple lifestyle, environmental and constitutional factors have been linked to the development of cognitive decline. For two interventions based on these factors, increasing physical activity and the control of hypertension, there is class 1 evidence for benefit. Other interventions based on these factors do not have the support of high-level evidence for the alteration of cognitive decline, but their other benefits would argue for their implementation. These interventions include increasing education, smoking cessation, avoiding head injuries, decreasing exposure to air pollution and increased social connections. As cognitive decline is experienced almost universally with ageing, and serious cognitive decline is experienced by substantial numbers of low-risk individuals, whole-of-population intervention strategies are the most effective and efficient. For other interventions to help prevent cognitive decline there is not sufficient evidence for their implementation to be recommended. These include alteration of alcohol ingestion, correction of hearing loss, treatment of depression, dietary interventions, menopausal hormone treatment and monoclonal antibodies directed against amyloid-β.
PubMed: 38943792
DOI: 10.1016/j.maturitas.2024.108062 -
Cell Reports Jun 2024Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation. A model cell system is constructed to induce ferroptosis by...
Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation. A model cell system is constructed to induce ferroptosis by re-expressing the transcription factor BACH1, a potent ferroptosis inducer, in immortalized mouse embryonic fibroblasts (iMEFs). The transfer of the culture supernatant from ferroptotic iMEFs activates the proliferation of hepatoma cells and other fibroblasts and suppresses cellular senescence-like features. The BACH1-dependent secretion of the longevity factor FGF21 is increased in ferroptotic iMEFs. The anti-senescent effects of the culture supernatant from these iMEFs are abrogated by Fgf21 knockout. BACH1 activates the transcription of Fgf21 by promoting ferroptotic stress and increases FGF21 protein expression by suppressing its autophagic degradation through transcriptional Sqstm1 and Lamp2 repression. The BACH1-induced ferroptotic FGF21 secretion suppresses obesity in high-fat diet-fed mice and the short lifespan of progeria mice. The inhibition of these aging-related phenotypes can be physiologically significant regarding ferroptosis.
PubMed: 38943639
DOI: 10.1016/j.celrep.2024.114403 -
Aging Jun 2024This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related...
This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.
PubMed: 38943627
DOI: 10.18632/aging.205920