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1.
Technol Health Care ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39031415

ABSTRACT

BACKGROUND: The Stepped Care Model (SCM) is an evidence-based treatment approach that tailors treatment intensity based on patients' health status, aiming to achieve the most positive treatment outcomes with the least intensive and cost-effective interventions. Currently, the effectiveness of the Stepped Care Model in postoperative rehabilitation for TKA (Total Knee Arthroplasty) patients has not been reported. OBJECTIVE: The present study aimed to investigate whether the stepped care model could improve early-stage self-report quality of life and knee function after total knee arthroplasty via a prospective randomized controlled design. METHODS: It was a mono-center, parallel-group, open-label, prospective randomized controlled study. Patients who aging from 60-75 years old as well as underwent unilateral primary total knee arthroplasty due to end-stage knee osteoarthritis between 2020.06 to 2022.02 were enrolled. Participants were randomized and arranged into two groups in a 1:1 allocation. The control group was given traditional rehabilitation guidance, while the stepped care model group was given continued stepped care. Hospital for special surgery knee score, daily living ability (ADL), knee flexion range, and adverse events at 1, 3, and 6 months after total knee arthroplasty were recorded. RESULTS: 88 patients proceeded to the final analysis. There was no significant difference of age, gender, length of stay, BMI, and educational level between the two groups at the baseline. After specific stepped care model interventions, patients showed significant improvements in HHS in 1 month (85.00 (82.25, 86.00) vs. 80.00 (75.00, 83.00), p< 0.001), 3 months (88.00 (86.00, 92.00) vs. 83.00 (76.75, 85.00), p< 0.001), and 6 months (93.00 (90.25, 98.00) vs. 88.00 (84.25, 91.75), p< 0.001) when compared with the control group. Similar results were also found in both daily living ability and knee flexion angle measurements. No adverse event was observed during the follow-up. CONCLUSION: The present study found that the stepped care model intervention significantly improved early-stage knee function and self-reported life quality after total knee arthroplasty due to knee osteoarthritis. Female patients and those less than 70 years old benefit more from the stepped care model intervention after total knee arthroplasty.

2.
J Cardiovasc Pharmacol ; 84(1): 18-25, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38968565

ABSTRACT

ABSTRACT: Recent studies have revealed the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in patients with AMI were included. The mean difference and/or odds ratio (OR) with 95% confidence intervals were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%; otherwise, a random-effects model was employed. Four randomized controlled trials and 4 observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (OR = 0.50, 95% CI: 0.32-0.80) and all-cause death (OR = 0.65, 95% CI: 0.44-0.95) compared with those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (mean difference = 1.90, 95% CI: 1.62-2.17) and a greater reduction of N-terminal prohormone of brain natriuretic peptide (OR = 0.88, 95% CI 0.82-0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI; SGLT2i may serve as an additional therapeutic option for patients with AMI, regardless of the presence or absence of diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Myocardial Infarction , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Treatment Outcome , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Myocardial Infarction/diagnosis , Male , Middle Aged , Female , Aged , Heart Failure/drug therapy , Heart Failure/mortality , Heart Failure/physiopathology , Heart Failure/diagnosis , Observational Studies as Topic , Risk Factors , Risk Assessment , Recovery of Function , Time Factors
3.
Int J Cardiol ; 413: 132359, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004352

ABSTRACT

BACKGROUND: Studies have revealed the beneficial effects of sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of heart failure (HF) regardless of the presence of diabetes. Besides, SGLT2i can decrease the incidence of atrial fibrillation (AF) in a broad population. However, the effects of SGLT2i on AF recurrence following catheter ablation (CA) remain uncertain. Therefore, this meta-analysis was undertaken to elucidate the effects of SGLT2i on AF recurrence after CA in AF patients. METHODS: A comprehensive search of PubMed, Embase, and Cochrane library was conducted for relevant studies, encompassing data from inception until March 20, 2024. The data were pooled using a fixed-effects model if the I2 value was <50%; otherwise, a random-effects model was adopted. RESULTS: One randomized controlled trial (RCT) and five observational studies involving 5623 patients with AF who underwent CA were included. SGLT2i treatment was associated with a significantly lower rate of AF recurrence (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.31-0.66). Subgroup analysis demonstrated that patients treated with SGLT2i exhibited a lower incidence of AF recurrence compared to those treated with dipeptidyl peptidase-4 inhibitors (DPP4i). The favorable effects of SGLT2i on AF recurrence were more pronounced in male patients and patients with persistent AF. CONCLUSIONS: This meta-analysis provided evidence supporting the effectiveness of SGLT2i in reducing the risk of AF recurrence after CA in AF patients. SGLT2i may serve as an additional therapy option in this population.

4.
Free Radic Biol Med ; 222: 569-578, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39009245

ABSTRACT

Mitophagy is a mechanism that maintains mitochondrial integrity and homeostasis and is thought to promote longevity and reduce the risk of age-related neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigate the abundance of mitochondrial reactive oxygen species (ROS), mitochondrial function, and mitophagy in primary fibroblasts from patients with sporadic AD (sAD) and normal healthy controls. The results show increased levels of mitochondrial ROS, changes in mitochondrial morphology, altered bioenergetic properties, and defects in autophagy, mitophagy, and lysosome-mediated degradation pathways in sAD fibroblasts relative to control fibroblasts. Interestingly, lysosome abundance and the staining of lysosomal markers remained high, while the capacity of lysosome-dependent degradation was lower in sAD fibroblasts than in controls fibroblasts. Nicotinamide riboside supplementation decreased mitochondrial ROS, while capacity for lysosomal degradation remained unchanged in sAD fibroblasts relative to healthy control fibroblasts. These findings provide insight into molecular mechanisms involving the dysregulation of lysosome and autophagy/mitophagy pathways that may contribute significantly to clinical signs and pathological features of sAD.

5.
Cell Death Discov ; 10(1): 337, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048556

ABSTRACT

Epirubicin (EPI) is effective in the treatment of malignant cancers, but its application is limited by life-threatening cardiotoxicity. Iron homeostasis disturbance has been implicated in anthracycline induced cardiotoxicity (AIC), and ferroptosis is involved in AIC which dependent upon intracellular iron. However, the role and exact mechanisms of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity (EIC) remain elusive. In this study, we aimed to investigate mechanisms underlying ferroptosis-driven EIC. Epirubicin triggered ferroptosis both in vivo and in cultured cardiomyocytes, and pretreatment with ferroptosis inhibitor, Ferrostatin-1(Fer-1) alleviates EIC. Microarray analysis was performed to screen for potential molecules involved in EIC in neonatal primary mouse ventricular cardiomyocytes (NMVMs). We found that the transcript level of ATP6V0A2, a subunit of vacuolar ATPase (V-ATPase), was significantly downregulated when NMVMs were subjected to EPI, which was verified in vivo and in vitro as measured by real time quantitative reverse transcription PCR (qRT-PCR) and immunoblotting. Intriguingly, overexpression of ATP6V0A2 effectively decreased excessive oxidative stress and lipid-peroxidation accumulation, thereby inhibiting ferroptosis and protecting cardiomyocytes against EIC, as evidenced by functional, enzymatic, and morphological changes. Mechanistically, forced expression of ATP6V0A2 restored lysosomal acidification in EPI-treated cardiomyocytes and protected cardiomyocytes and mice hearts from ferroptosis-driven EIC. In this study, our data elucidate that ferroptosis is involved in EIC, which is ignited by ATP6V0A2-dependent lysosomal acidification dysfunction. Our study provides a new potential therapeutic target for ameliorating EIC.

6.
Angew Chem Int Ed Engl ; : e202404599, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023389

ABSTRACT

Spatiotemporally controlled two-photon photodegradation of hydrogels has gained increasing attention for high-precision subtractive tissue engineering. However, conventional photolabile hydrogels often have poor efficiency upon two-photon excitation in the near-infrared (NIR) region and thus require high laser dosage that may compromise cell activity. As a result, high-speed two-photon hydrogel erosion in the presence of cells remains challenging. Here we introduce the design and synthesis of efficient coumarin-based photodegradable hydrogels to overcome these limitations. A set of photolabile coumarin-functionalized polyethylene glycol linkers are synthesized through a Passerini multicomponent reaction. After mixing these linkers with thiolated hyaluronic acid, semi-synthetic photodegradable hydrogels are formed in situ via Michael addition crosslinking. The efficiency of photodegradation in these hydrogels is significantly higher than that in nitrobenzyl counterparts upon two-photon irradiation at 780 nm. A complex microfluidic network mimicking the bone microarchitecture is successfully fabricated in preformed coumarin hydrogels at high speeds of up to 300 mm s-1 and low laser dosage down to 10 mW. Further, we demonstrate fast two-photon printing of hollow microchannels inside a hydrogel to spatiotemporally direct cell migration in 3D. Collectively, these hydrogels may open new avenues for fast laser-guided tissue fabrication at high spatial resolution.

7.
Macromol Rapid Commun ; : e2400241, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871361

ABSTRACT

Metal-organic frameworks (MOFs) have shown great research and application value in various types of hydrosilylation reactions. However, studies on photocatalysis-induced hydrosilylation using MOFs are extremely rare. Metal nanoparticles (MNPs)@MOFs are extensively studied for their excellent structural tunability and photocatalytic activity, but there are few reports on their application in photocatalytic hydrosilylation. Here, a novel photocatalyst consisting of platinum (Pt) nanoparticles immobilized in a MOF framework is synthesized and used for photocatalytic hydrosilylation. The effects of various factors on hydrosilylation conversion are investigated, including catalyst concentration, substrate ratio, and irradiation intensity. Furthermore, the photoreactivity of the synthesized Pt catalyst is evaluated in the presence of different concentrations of 2-chlorothixanthone as a photosensitizer. It is noteworthy that the conversion of the reaction increases with increasing catalyst concentration or photosensitizer concentration, whereas increasing the polymethylhydrosiloxane content does not lead to a significant increase in conversion. This study demonstrates the potential of MNPs@MOFs as efficient photocatalysts for photoinduced hydrosilylation reactions and paves the way for future applications in this area.

8.
Alzheimers Dement ; 20(6): 4212-4233, 2024 06.
Article in English | MEDLINE | ID: mdl-38753870

ABSTRACT

BACKGROUND: Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown. METHODS: We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches. RESULTS: Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aß) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD. CONCLUSIONS: Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA. HIGHLIGHTS: Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.


Subject(s)
Alzheimer Disease , Coumarins , Disease Models, Animal , Lysosomes , Mice, Transgenic , Mitophagy , Alzheimer Disease/drug therapy , Animals , Coumarins/pharmacology , Coumarins/therapeutic use , Lysosomes/drug effects , Lysosomes/metabolism , Mice , Mitophagy/drug effects , Amyloid beta-Peptides/metabolism , Cognition/drug effects
9.
Food Chem ; 448: 139088, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38547707

ABSTRACT

The duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRMHR) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R2Xcum, R2Ycum and Q2cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R2) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation.


Subject(s)
Camellia sinensis , Food Storage , Metabolomics , Tea , Tea/chemistry , Multivariate Analysis , Camellia sinensis/chemistry , Discriminant Analysis , Catechin/analysis , Catechin/chemistry , Amino Acids/analysis , Amino Acids/chemistry , Alkaloids/analysis , Alkaloids/chemistry , Chromatography, High Pressure Liquid , Plant Extracts/chemistry , Plant Extracts/analysis
10.
Geroscience ; 46(2): 1641-1655, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37713088

ABSTRACT

Aging is a risk factor for human health and quality of life. Screening and development of novel supplements and medications to combat aging and delay the incidence of age-related diseases are of great significance. In this study, salidroside (SA), a primary natural small molecule from Rhodiola rosea, was investigated regarding its effects on life and healthspan and the underlying molecular mechanism(s) of anti-aging and antioxidation. Our results showed that SA effectively prolonged lifespan and exhibited anti-aging and antioxidative properties. Computer-assisted methods, label-free interaction analysis, and in vitro assays showed that SA directly bound heat shock protein 90 (HSP90). Furthermore, SA significantly inhibited the ATPase activity of HSP90, affecting the interaction between HSP90 and its interacting proteins and the expression of downstream genes to regulate lifespan and the oxidative stress response. Our findings provided new insights into the pharmacological properties of SA across multiple species and its potential as an anti-aging drug.


Subject(s)
Glucosides , Longevity , Phenols , Quality of Life , Humans , Oxidative Stress , Antioxidants/pharmacology
11.
Small ; 20(12): e2307685, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37946630

ABSTRACT

The rational design of metal-organic framework (MOF)-based electrocatalysts plays a key role in achieving high-efficiency oxygen evolution reaction (OER). Herein, a synergetic morphology and electronic structure engineering strategy are proposed to design a Co-MOF nanoflower grown on carbon paper via rare-earth cerium doping (CoCe-MOF/CP). Compared with Co-MOF/CP, the developed CoCe-MOF/CP exhibited superior OER performance with a low overpotential of 267 mV at 10 mA cm-2 and outstanding long-term stability over 100 h. Theoretical calculations show that the unique 4f valence electron structure of Ce induced charge redistribution of the Co-MOF surface through the strong Co 3d-O 2p-Ce 4f orbital electronic coupling below the Fermi level. Ce-doped plays a key role in the engineering of the electronic states of the Co sites to endow them with the optimal free energy landscape for enhanced OER catalytic activity. This work provides new insights into comprehending the RE-enhanced mechanism of electrocatalysis and provides an effective strategy for the design of MOF-based electrocatalysts.

12.
Aging Cell ; 23(1): e13942, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37497653

ABSTRACT

Current research on human aging has largely been guided by the milestone paper "hallmarks of aging," which were first proposed in the seminal 2013 paper by Lopez-Otin et al. Most studies have focused on one aging hallmark at a time, asking whether the underlying molecular perturbations are sufficient to drive the aging process and its associated phenotypes. More recently, researchers have begun to investigate whether aging phenotypes are driven by concurrent perturbations in molecular pathways linked to not one but to multiple hallmarks of aging and whether they present different patterns in organs and systems over time. Indeed, preliminary results suggest that more complex interactions between aging hallmarks must be considered and addressed, if we are to develop interventions that successfully promote healthy aging and/or delay aging-associated dysfunction and diseases. Here, we summarize some of the latest work and views on the interplay between hallmarks of aging, with a specific focus on mitochondrial dysfunction. Indeed, this represents a significant example of the complex crosstalk between hallmarks of aging and of the effects that an intervention targeted to a specific hallmark may have on the others. A better knowledge of these interconnections, of their cause-effect relationships, of their spatial and temporal sequence, will be very beneficial for the whole aging research field and for the identification of effective interventions in promoting healthy old age.


Subject(s)
Aging , Mitochondrial Diseases , Humans , Aging/genetics , Phenotype
13.
Food Res Int ; 173(Pt 1): 113238, 2023 11.
Article in English | MEDLINE | ID: mdl-37803551

ABSTRACT

It's generally believed that the longer the storage, the better the quality of dark tea, but the chemical differences of Qingzhuan tea (QZT) with different storage years is still unclear. Herein, in this work, an untargeted metabolomic approach based on SWATH-MS was established to investigate the differential compounds of QZT with 0-9 years' storage time. These QZT samples were roughly divided into two categories by principal component analysis (PCA). After orthogonal projections to latent structures discriminant analysis (OPLS-DA), 18 differential compounds were putatively identified as chemical markers for the storage year variation of QZT. Heatmap visualization showed that the contents of catechins, fatty acids, and some phenolic acids significantly reduced, flavonoid glycosides, triterpenoids, and 8-C N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) increased with the increase of storage time. Furthermore, these chemical markers were verified by the peak areas corresponding to MS2 ions from SWATH-MS. Based on the extraction chromatographic peak areas of MS and MS2 ions, a duration time prediction model was built for QZT with correlation coefficient R2 of 0.9080 and 0.9701, and RMSEP value of 0.85 and 1.24, respectively. This study reveals the chemical differences of QZT with different storage years and provides a theoretical basis for the quality evaluation of stored dark tea.


Subject(s)
Catechin , Tea , Tea/chemistry , Flavonoids/analysis , Metabolomics/methods , Catechin/analysis , Ions
14.
Nutrients ; 15(20)2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37892459

ABSTRACT

Polyphenols, a class of bioactive compounds with phenolic structures, are abundant in human diets. They have gained attention in biomedical fields due to their beneficial properties, including antioxidant, antibacterial, and anti-inflammatory activities. Therefore, polyphenols can prevent multiple chronic or infectious diseases and may help in the prevention of oral diseases. Oral health is crucial to our well-being, and maintaining a healthy oral microbiome is essential for preventing various dental and systemic diseases. However, the mechanisms by which polyphenols modulate the oral microbiota and contribute to oral health are still not fully understood, and the application of polyphenol products lies in different stages. This review provides a comprehensive overview of the advancements in understanding polyphenols' effects on oral health: dental caries, periodontal diseases, halitosis, and oral cancer. The mechanisms underlying the preventive and therapeutic effects of polyphenols derived from dietary sources are discussed, and new findings from animal models and clinical trials are included, highlighting the latest achievements. Given the great application potential of these natural compounds, novel approaches to dietary interventions and oral disease treatments may emerge. Moreover, investigating polyphenols combined with different materials presents promising opportunities for developing innovative therapeutic strategies in the treatment of oral diseases.


Subject(s)
Dental Caries , Microbiota , Animals , Humans , Polyphenols/pharmacology , Polyphenols/therapeutic use , Polyphenols/chemistry , Oral Health , Dental Caries/prevention & control , Diet
15.
Heliyon ; 9(6): e17392, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37484291

ABSTRACT

Replication stress, caused by Rev1 deficiency, is associated with mitochondrial dysfunction, and metabolic stress. However, the overall metabolic alterations and possible interventions to rescue the deficits due to Rev1 loss remain unclear. Here, we report that loss of Rev1 leads to intense changes in metabolites and that this can be manipulated by NAD + supplementation. Autophagy decreases in Rev1-/- mouse embryonic fibroblasts (MEFs) and can be restored by supplementing the NAD+ precursor nicotinamide riboside (NR). The abnormal mitochondrial morphology in Rev1-/- MEFs can be partially reversed by NR supplementation, which also protects the mitochondrial cristae from rotenone-induced degeneration. In nematodes rev-1 deficiency causes sensitivity to oxidative stress but this cannot be rescued by NR supplementation. In conclusion, Rev1 deficiency leads to metabolic dysregulation of especially lipid and nucleotide metabolism, impaired autophagy, and mitochondrial anomalies, and all of these phenotypes can be improved by NR replenishment in MEFs.

16.
Front Aging Neurosci ; 15: 1101216, 2023.
Article in English | MEDLINE | ID: mdl-37358952

ABSTRACT

Background: The growing prevalence of Alzheimer's disease (AD) is becoming a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have recently been suggested as etiological factors in AD, in association with abnormalities in components of the autophagic machinery like lysosomes and phagosomes. Several large transcriptomic studies have been performed on different brain regions from AD and healthy patients, and their data represent a vast source of important information that can be utilized to understand this condition. However, large integration analyses of these publicly available data, such as AD RNA-Seq data, are still missing. In addition, large-scale focused analysis on mitophagy, which seems to be relevant for the aetiology of the disease, has not yet been performed. Methods: In this study, publicly available raw RNA-Seq data generated from healthy control and sporadic AD post-mortem human samples of the brain frontal lobe were collected and integrated. Sex-specific differential expression analysis was performed on the combined data set after batch effect correction. From the resulting set of differentially expressed genes, candidate mitophagy-related genes were identified based on their known functional roles in mitophagy, the lysosome, or the phagosome, followed by Protein-Protein Interaction (PPI) and microRNA-mRNA network analysis. The expression changes of candidate genes were further validated in human skin fibroblast and induced pluripotent stem cells (iPSCs)-derived cortical neurons from AD patients and matching healthy controls. Results: From a large dataset (AD: 589; control: 246) based on three different datasets (i.e., ROSMAP, MSBB, & GSE110731), we identified 299 candidate mitophagy-related differentially expressed genes (DEG) in sporadic AD patients (male: 195, female: 188). Among these, the AAA ATPase VCP, the GTPase ARF1, the autophagic vesicle forming protein GABARAPL1 and the cytoskeleton protein actin beta ACTB were selected based on network degrees and existing literature. Changes in their expression were further validated in AD-relevant human in vitro models, which confirmed their down-regulation in AD conditions. Conclusion: Through the joint analysis of multiple publicly available data sets, we identify four differentially expressed key mitophagy-related genes potentially relevant for the pathogenesis of sporadic AD. Changes in expression of these four genes were validated using two AD-relevant human in vitro models, primary human fibroblasts and iPSC-derived neurons. Our results provide foundation for further investigation of these genes as potential biomarkers or disease-modifying pharmacological targets.

17.
Pestic Biochem Physiol ; 192: 105388, 2023 May.
Article in English | MEDLINE | ID: mdl-37105617

ABSTRACT

Juvenile hormone (JH) plays a crucial endocrine regulatory role in insect metamorphosis, reproduction, and longevity in multiple organisms, such as flies, honeybees, and migratory monarch butterflies. However, the molecular mechanism of JH affecting longevity remains largely unknown. In this study, we showed that JH III and its analog methoprene shortened the survival days significantly in the adulthood of male silkworm. At the same time, the allatostatin, a neuropeptide that inhibits the secretion of JH by the corpora allata, could extend the survival days dramatically after adult eclosion in male silkmoth. Interestingly, a central pro-longevity FoxO transcription factor was reduced upon JH stimulation in silkworm individuals and BmN-SWU1 cells. Furthermore, the analysis of the upstream sequence of the FoxO gene identified a JH response element which suggested that FoxO might be regulated as a target of JH. Surprisingly, we identified a Bmtakeout (BmTO) gene that encodes a JH-binding protein and contains a FoxO response element. As expected, FoxO overexpression and knockdown up- and down-regulated the expression of BmTO respectively, indicating that BmTO functions as a FoxO target. BmTO overexpression could release the inhibitory effect of JH on the BmFoxO gene by reducing JH bioavailability to block its signal transduction. Collectively, these results may provide insights into the mechanism of the JH-FoxO-TO axis in aging research and pest control.


Subject(s)
Bombyx , Butterflies , Animals , Juvenile Hormones/pharmacology , Juvenile Hormones/metabolism , Bombyx/genetics , Bombyx/metabolism , Longevity , Metamorphosis, Biological
18.
ACS Omega ; 8(6): 5820-5835, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36816686

ABSTRACT

Organic-rich shales and mudstones have long been investigated regarding the control of source, environment, climate, etc. on the enrichment of organic carbon. However, little is documented about how autotrophy and heterotrophy influence organic carbon cycling/export. Here, we show molecular and carbon isotopic compositional changes of the shale or mudstone source rocks from the Chang 3 to 7 members of the Yanchang Formation. The Chang 7 member source rocks have higher quality (480-500 mg/g) and total organic carbon (TOC) (15.3% on average) than other member source rocks; the sterane/hopane ratio and the δ13C of organic carbon and kerogen decrease from the Chang 3 to 7 members, but Δδ ([average δ13C of n-C17 + n-C18] - [average δ13C of pristane + phytane]) increases, and no aryl isoprenoids and C40 aromatic carotenoids (e.g., isorenieratane) were observed. These low maturity biomarker features suggest that there were no water stratification, photic zone euxinia (PZE), and no obvious change in the organic matter source, and the water column is generally anoxic. A comparison of the δ13C of Pr and Ph with the δ13C of the n-C17 and n-C18 alkanes reveals a shift in the mode of carbon cycling/export (autotrophy versus heterotrophy) in the Yanchang Formation and that there was dominant heterotrophic bacterial activity or bacterial biomass in the Chang 7 member. The TOC spike in the Chang 7 member may result from boosted carbon cycling/export that improves organic carbon preservation than other members. Possible external forcings on the shift are abundant hydrothermal- or volcanic-derived metal salts as electron acceptors in the palaeowater, which is a reasonable explanation for enhanced heterotrophic bacterial activity. This finding improves our understanding of heterotrophic bacterial activity control on organic matter (OM) preservation and may be a significant supplement for understanding the ecological or environmental forcings in the Yanchang Formation, Ordos Basin.

19.
ACS Macro Lett ; 12(2): 263-268, 2023 Feb 21.
Article in English | MEDLINE | ID: mdl-36734851

ABSTRACT

A coumarinacyl anilinium (CAA) salt, facilely synthesized via a one-pot reaction, is shown to be a versatile visible and NIR photoinitiator for cationic and step-growth polymerizations. CAA salt exhibits superior photoinitiation performance as compared to commercial iodonium salt in cationic polymerization. Upon visible-light irradiation, this salt undergoes hemolytic and heterolytic cleavage and subsequent electron transfer and hydrogen abstraction reactions, forming reactive species capable of initiating cationic polymerization of epoxides and vinyl monomers. After a short irradiation period, polymerization also proceeds in the dark due to the non-nucleophilic nature of the counteranion. NIR-induced polymerizations were successfully conducted based on upconversion photochemistry. CAA salt can also initiate step-growth polymerization of N-ethyl carbazole (NEC) by oxidation of the monomer by the photochemically formed anilium radical cations. Subsequent proton release and radical coupling reactions essentially yield polycarbazole. CAA salt, featuring straightforward synthesis and long-wavelength sensitivity as well as versatile photoinitiating performance, has great potential in various applications.

20.
Am J Transl Res ; 14(10): 7226-7232, 2022.
Article in English | MEDLINE | ID: mdl-36398228

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures. METHODS: Retrospective study of 158 elderly patients with hip fractures who underwent artificial femoral head replacement in our hospital from March 2016 to July 2019 were enrolled. According to the unified discharge standards, patients were divided into the observation (65 cases who met discharge criteria) and control group (93 cases who failed to meet all discharge criteria). Histopathological feature, operation status, postoperative Harris Hip score, therapeutic outcome, postoperative complications, readmission and mortality rate were compared between the two groups. RESULTS: Surgery duration and intraoperative blood loss exhibited no difference between the two groups, while transfusion volume and length of hospital stay were significantly increased in the observation group. There was no significant difference in the Harris Hip score between the two groups 12 months postoperatively. The incidence of postoperative complications during the follow-up period was notably lower in the observation group. In addition, the three-month readmission rate and one-year mortality rate were significantly lower in the observation group. CONCLUSIONS: For elderly patients with hip fractures undergoing artificial femoral head replacement, the incidence of postoperative complications and postoperative readmission/mortality rate could be reduced through the establishment of unified discharge standards, which should be used in future clinical practice.

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