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1.
Int J Biol Macromol ; 276(Pt 1): 133736, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992543

ABSTRACT

Pea peptides can lead to degradation through oxidation, deamidation, hydrolysis, or cyclization during production, processing, and storage, which in turn limit their broader application. To stabilize pea peptides, this study employed spray drying technology to create a pea peptide micro-encapsule using maltodextrin, gum tragacanth, and pea peptides. Four key factors, including polysaccharide ratio, glycopeptide ratio, solid-liquid ratio, and inlet temperature, were optimized to enhance the antioxidant properties of the pea peptide micro-encapsule. The results indicated that the utilization of maltodextrin and gum tragacanth significantly improves the storage stability and antioxidant activity of pea peptides. Moreover, optimal storage stability for pea peptides was achieved with a polysaccharide ratio of 9:1, a glycopeptide ratio of 10:1, a solid-liquid ratio of 4:40, and an inlet temperature of 180 °C. After 60 days of storage, the encapsulated pea peptides maintained 70.22 %, 25.19 %, and 40.32 % for scavenging abilities to hydroxyl radical, superoxide anion, and ABTS radical, respectively. In contrast, the unencapsulated pea peptides showed a decline to 47.02 %, 0 %, and 24.46 % in the same antioxidant activities after storage. These findings underscore the potential of spray drying technology to enhance the functional properties of pea peptides for various applications.

2.
Plant Physiol Biochem ; 214: 108940, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39024781

ABSTRACT

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

3.
Front Biosci (Landmark Ed) ; 29(6): 233, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38940043

ABSTRACT

BACKGROUND: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth. METHODS: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array. RESULTS: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth. CONCLUSIONS: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.


Subject(s)
Cell Survival , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Melanoma , Humans , Endoplasmic Reticulum Stress/genetics , Endoplasmic Reticulum Stress/drug effects , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Cell Death/genetics , Apoptosis/genetics , Apoptosis/drug effects , Cell Proliferation/genetics , Cell Proliferation/drug effects , Membrane Proteins
4.
JMIR Public Health Surveill ; 10: e54485, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848124

ABSTRACT

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.


Subject(s)
Acute Coronary Syndrome , Fibrinogen , Humans , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/blood , Fibrinogen/analysis , Male , Female , Prospective Studies , Middle Aged , Aged , Risk Factors , Biomarkers/blood
5.
Angew Chem Int Ed Engl ; : e202407304, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898368

ABSTRACT

Controlling the structure and chemistry of solid electrolyte interphase (SEI) underpins the stability of electrolyte-electrode interface, and is crucial for advancing rechargeable lithium metal batteries (LMBs). Here, we utilized photo-controlled copolymerization to achieve the on-demand synthesis of fluorosulfonyl fluoropolymers as unprecedented artificial SEI layers on Li metal anodes. This work not only enables instant formation of a hybrid polymer-inorganic interphase that consists of a polymer-enriched top layer and a LiF-fortified bottom layer, originating from a single polymeric component, but also imparts various desirable physical properties (e.g., good mechanical strength and flexibility, high ion conductivity, low overpotential) to SEI via a single-to-divergent strategy. Model reactions and structural characterizations supported the formation of a divergent fluorinated interphase, which furnished prolonged stabilization of Li deposition, high coulombic efficiency and improved cycling behavior in electrochemical experiments. This work highlights the great potential of exploring reactive polymers as versatile coatings to stabilize Li metal anodes, providing a promising avenue to solve electrode-electrolyte interfacial problems for LMBs.

6.
Circulation ; 149(25): 2002-2020, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38885303

ABSTRACT

Myocardial infarction is a cardiovascular disease characterized by a high incidence rate and mortality. It leads to various cardiac pathophysiological changes, including ischemia/reperfusion injury, inflammation, fibrosis, and ventricular remodeling, which ultimately result in heart failure and pose a significant threat to global health. Although clinical reperfusion therapies and conventional pharmacological interventions improve emergency survival rates and short-term prognoses, they are still limited in providing long-lasting improvements in cardiac function or reversing pathological progression. Recently, cardiac patches have gained considerable attention as a promising therapy for myocardial infarction. These patches consist of scaffolds or loaded therapeutic agents that provide mechanical reinforcement, synchronous electrical conduction, and localized delivery within the infarct zone to promote cardiac restoration. This review elucidates the pathophysiological progression from myocardial infarction to heart failure, highlighting therapeutic targets and various cardiac patches. The review considers the primary scaffold materials, including synthetic, natural, and conductive materials, and the prevalent fabrication techniques and optimal properties of the patch, as well as advanced delivery strategies. Last, the current limitations and prospects of cardiac patch research are considered, with the goal of shedding light on innovative products poised for clinical application.


Subject(s)
Myocardial Infarction , Humans , Myocardial Infarction/therapy , Myocardial Infarction/physiopathology , Animals , Tissue Scaffolds
7.
Angew Chem Int Ed Engl ; : e202408611, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38924225

ABSTRACT

Controlled radical copolymerizations present attractive avenues to obtain polymers with complicated compositions and sequences. In this work, we report the development of a visible-light-driven organocatalyzed controlled copolymerization of fluoroalkenes and acyclic N-vinylamides for the first time. The approach enables the on-demand synthesis of a broad scope of amide-functionalized main-chain fluoropolymers via novel fluorinated thiocarbamates, facilitating regulations over chemical compositions and alternating fractions by rationally selecting comonomer pairs and ratios. This method allows temporally controlled chain-growth by external light, and maintains high chain-end fidelity that promotes facile preparation of block sequences. Notably, the obtained F/N hybrid polymers, upon hydrolysis, afford free amino-substituted fluoropolymers versatile for post modifications toward various functionalities (e.g., amide, sulfonamide, carbamide, thiocarbamide). We further demonstrate the in-situ formation of polymer networks with desirable properties as protective layers on lithium metal anodes, presenting a promising avenue for advancing lithium metal batteries.

8.
Talanta ; 275: 126069, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38692042

ABSTRACT

Lipid deposition has been considered one of the key factors in the occurrence of valvular heart disease (VHD) and a great potential target for the diagnosis of VHD. However, the development of lipid imaging technologies and efficient lipid specific probes is in urgent demand. In this work, we have prepared a lipid droplets (LDs) targeted fluorescence probe CPTM based on a push-pull electronic structure for the imaging of diseased aortic valves. CPTM showed obvious twisted intramolecular charge transfer (TICT) effect and its emission changed from 600 nm in water to 508 nm in oil. CPTM not only exhibited good biocompatibility and high photostability, but also impressive LDs specific imaging performance in human primary valvular interstitial cells and human diseased aortic valves. Moreover, the dynamic changes of intracellular LDs could be monitor in real-time after staining with CPTM. These results were expected to offer new ideals for the designing of novel LDs specific probes for further bioimaging applications.


Subject(s)
Aortic Valve , Fluorescent Dyes , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Optical Imaging , Lipid Droplets/chemistry , Color , Aortic Valve Disease/diagnostic imaging , Lipids/chemistry , Lipids/analysis
9.
Cytokine Growth Factor Rev ; 77: 91-103, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735805

ABSTRACT

Interleukin-17 (IL-17), a pivotal cytokine in immune regulation, has attracted significant attention in recent years due to its roles in various physiological and pathological processes. This review explores IL-17 in immunological context, emphasizing its structure, production, and signaling pathways. Specifically, we explore its involvement in inflammatory diseases and autoimmune diseases, with a notable focus on its emerging implications in cardiovascular system. Through an array of research insights, IL-17 displays multifaceted functions yet awaiting comprehensive discovery. Highlighting therapeutic avenues, we scrutinize the efficacy and clinical application of four marketed IL-17 mAbs along other targeted therapies, emphasizing their potential in immune-mediated disease management. Additionally, we discussed the novel IL-17D-CD93 axis, elucidating recent breakthroughs in their biological function and clinical implications, inviting prospects for transformative advancements in immunology and beyond.


Subject(s)
Autoimmune Diseases , Cardiovascular Diseases , Interleukin-17 , Humans , Interleukin-17/immunology , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Cardiovascular Diseases/immunology , Cardiovascular Diseases/therapy , Signal Transduction , Inflammation/immunology , Cardiovascular System/immunology , Antibodies, Monoclonal/therapeutic use
10.
Nucleic Acids Res ; 52(10): 5643-5657, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38716861

ABSTRACT

Genomic mutations allow bacteria to adapt rapidly to adverse stress environments. The three-dimensional conformation of the genome may also play an important role in transcriptional regulation and environmental adaptation. Here, using chromosome conformation capture, we investigate the high-order architecture of the Zymomonas mobilis chromosome in response to genomic mutation and ambient stimuli (acetic acid and furfural, derived from lignocellulosic hydrolysate). We find that genomic mutation only influences the local chromosome contacts, whereas stress of acetic acid and furfural restrict the long-range contacts and significantly change the chromosome organization at domain scales. Further deciphering the domain feature unveils the important transcription factors, Ferric uptake regulator (Fur) proteins, which act as nucleoid-associated proteins to promote long-range (>200 kb) chromosomal communications and regulate the expression of genes involved in stress response. Our work suggests that ubiquitous transcription factors in prokaryotes mediate chromosome organization and regulate stress-resistance genes in bacterial adaptation.


Subject(s)
Adaptation, Physiological , Bacterial Proteins , Chromosomes, Bacterial , Gene Expression Regulation, Bacterial , Transcription Factors , Adaptation, Physiological/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Chromosomes, Bacterial/chemistry , Chromosomes, Bacterial/genetics , Gene Expression Regulation, Bacterial/genetics , Mutation , Repressor Proteins/metabolism , Repressor Proteins/genetics , Stress, Physiological/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Zymomonas/genetics , Zymomonas/metabolism , Nucleic Acid Conformation
11.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2585-2596, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812159

ABSTRACT

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.


Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury , Cyclooxygenase 2 , Liver , NF-kappa B , Panax , Saponins , Signal Transduction , Animals , Acetaminophen/adverse effects , Acetaminophen/toxicity , Mice , Panax/chemistry , Male , Saponins/pharmacology , Saponins/administration & dosage , NF-kappa B/genetics , NF-kappa B/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Liver/drug effects , Liver/metabolism , Signal Transduction/drug effects , Humans , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology
12.
Article in English | MEDLINE | ID: mdl-38749449

ABSTRACT

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: To identify the incidence, predictors, and clinical outcomes of PVR following TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with severe Sievers type 1 BAV stenosis undergoing TAVR with current generation transcatheter heart valves (THVs) in 24 international centres were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAE), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%): mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were larger virtual raphe ring (VRR) perimeter (ORadj 1.07, 95% CI 1.02-1.13), severe annular or left ventricular outflow tract (LVOT) calcification (ORadj 5.21, 95% CI 1.45-18.77), self-expanding valve (ORadj 9.01, 95% CI 2.09-38.86), and intentional supra-annular THV positioning (ORadj 3.31, 95% CI 1.04-10.54). At a median follow-up of 1.3 [IQR 0.5-2.4] years, moderate or severe PVR was associated with an increased risk of MAE (HRadj 2.52, 95% CI 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAE during follow-up.

13.
Eur Heart J Digit Health ; 5(3): 219-228, 2024 May.
Article in English | MEDLINE | ID: mdl-38774374

ABSTRACT

Aims: Permanent pacemaker implantation and left bundle branch block are common complications after transcatheter aortic valve replacement (TAVR) and are associated with impaired prognosis. This study aimed to develop an artificial intelligence (AI) model for predicting conduction disturbances after TAVR using pre-procedural 12-lead electrocardiogram (ECG) images. Methods and results: We collected pre-procedural 12-lead ECGs of patients who underwent TAVR at West China Hospital between March 2016 and March 2022. A hold-out testing set comprising 20% of the sample was randomly selected. We developed an AI model using a convolutional neural network, trained it using five-fold cross-validation and tested it on the hold-out testing cohort. We also developed and validated an enhanced model that included additional clinical features. After applying exclusion criteria, we included 1354 ECGs of 718 patients in the study. The AI model predicted conduction disturbances in the hold-out testing cohort with an area under the curve (AUC) of 0.764, accuracy of 0.743, F1 score of 0.752, sensitivity of 0.876, and specificity of 0.624, based solely on pre-procedural ECG images. The performance was better than the Emory score (AUC = 0.704), as well as the logistic (AUC = 0.574) and XGBoost (AUC = 0.520) models built with previously identified high-risk ECG patterns. After adding clinical features, there was an increase in the overall performance with an AUC of 0.779, accuracy of 0.774, F1 score of 0.776, sensitivity of 0.794, and specificity of 0.752. Conclusion: Artificial intelligence-enhanced ECGs may offer better predictive value than traditionally defined high-risk ECG patterns.

14.
Article in English | MEDLINE | ID: mdl-38745381

ABSTRACT

Tricuspid regurgitation is a common valve disease with high incidence and poor prognosis. For elderly patients and those with a history of open heart surgery, second thoracotomy and valve replacement carry a high risk. Transcatheter tricuspid valve replacement (TTVR) has become an alternative treatment for patients with high surgical risk. LuX-Valve is a novel self-expandable valve that does not rely on radial force to anchor the valve annulus. The preliminary results have been satisfactory, and this technology is gradually being adopted in China and around the world. Successful implementation of this technique depends on echocardiographic preoperative screening, intraoperative guidance, and postoperative follow-up. The purpose of this article is to provide a state-of-the-art review of the key points and technical considerations for preoperative screening, intraoperative guidance, and postoperative follow-up for TTVR.

15.
EuroIntervention ; 20(9): 536-550, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726720

ABSTRACT

The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI..


Subject(s)
Consensus , Hemorrhage , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Risk Factors , Hemorrhage/etiology , Risk Assessment , Aortic Valve Stenosis/surgery , Aortic Valve/surgery
16.
World J Stem Cells ; 16(5): 538-550, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38817334

ABSTRACT

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

17.
Ultrason Sonochem ; 107: 106888, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38697875

ABSTRACT

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

18.
J Colloid Interface Sci ; 667: 520-528, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38653073

ABSTRACT

Fluorescent probes that specifically targeting Lipid droplets (LDs) have shown potential in biological imaging. Albeit, their in vivo applications are limited due to the hydrophobicity, low signal-to-noise ratio (SNR) and LDs-specificity. Thus, we designed a novel probe namely MeOND, and a reactive oxygen species (ROS)-responsive nano-platform to improve in vivo LDs-specific imaging. MeOND exhibits a remarkable twisted intramolecular charge transfer (TICT) effect with a strongly enhanced near-infrared emission in low-polarity lipid environment. Also, MeOND demonstrates satisfactory biocompatibility and superior intracellular LDs imaging capabilities. MeOND encapsulated nano-platform (MeOND@PMM) presented favorable water solubility and biocompatibility. MeOND@PMM remains stable in physiological conditions but quickly degrades in the environment of elevated ROS level. The released MeOND could then light up the intracellular LDs in atherosclerotic plaques. The design of the probe and nano-platform is expected to provide a better tool for the scientific research of LDs and LDs-related diseases.


Subject(s)
Atherosclerosis , Fluorescent Dyes , Optical Imaging , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Atherosclerosis/diagnostic imaging , Atherosclerosis/metabolism , Fluorescent Dyes/chemistry , Animals , Mice , Lipid Droplets/chemistry , Lipid Droplets/metabolism , Nanoparticles/chemistry , Humans , Particle Size , RAW 264.7 Cells , Surface Properties
19.
Am J Case Rep ; 25: e943687, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38676296

ABSTRACT

BACKGROUND Hepatic hydatid cyst disease, caused by the parasite Echinococcus granulosus, is endemic in certain rural areas of the world, but not in most of East Asia outside Mainland China. In Taiwan, only one autochthonous case has been reported over the past 40 years. We present the case of an urban 91-year-old female patient without international travel history for more than 40 years. CASE REPORT The 91-year-old woman who used a wheelchair came to the Emergency Department reporting melena for 2 days and 1 episode of coffee-grounds vomitus. Epigastric tenderness was present. An incidental finding of elevated liver enzymes along with the clinical picture prompted further survey. Computed tomography revealed a 14×10×12 cm homogeneous cystic lesion in the right hepatic lobe with a partially calcified wall. On sonograms, a similar lesion was found, and the pathognomic "water-lily" sign was visualized along with the isoechoic-to-hypoechoic internal septa, fulfilling the diagnosis despite the patient's refusal to undergo magnetic resonance imaging studies and invasive definite diagnostic procedures. Although anthelmintic chemotherapy and invasive therapeutic measures were also refused, her symptoms improved and was not recurrent under supportive measures. However, the cyst was still present 12 months after discharge. CONCLUSIONS The case highlights that in areas with few cases of hepatic hydatid disease, the accurate diagnosis could be missed in patients without a significant epidemiological history. However, once imaging findings, especially those that are pathognomic, are appropriately interpreted on at least 2 imaging modalities, such cases could be diagnosed without further definitive studies.


Subject(s)
Echinococcosis, Hepatic , Humans , Female , Echinococcosis, Hepatic/diagnosis , Echinococcosis, Hepatic/diagnostic imaging , Taiwan , Aged, 80 and over , Tomography, X-Ray Computed
20.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167158, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38588780

ABSTRACT

OBJECTIVES: Diabetic cardiomyopathy (DCM) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients, with its underlying mechanisms still elusive. This study aims to investigate the role of cholesterol-25-monooxygenase (CH25H) in T2DM induced cardiomyopathy. METHODS: High fat diet combined with streptozotocin (HFD/STZ) were used to establish a T2DM model. CH25H and its product 25-hydroxycholesterol (25HC) were detected in the hearts of T2DM model. Gain- or loss-of-function of CH25H were performed by receiving AAV9-cTNT-CH25H or CH25H knockout (CH25H-/-) mice with HFD/STZ treatment. Cardiac function was evaluated using echocardiography, and cardiac tissues were collected for immunoblot analysis, histological assessment and quantitative polymerase chain reaction (qPCR). Mitochondrial morphology and function were evaluated using transmission electron microscopy (TEM) and Seahorse XF Cell Mito Stress Test Kit. RNA-sequence analysis was performed to determine the molecular changes associated with CH25H deletion. RESULTS: CH25H and 25HC were significantly decreased in the hearts of T2DM mice. CH25H-/- mice treated with HFD/STZ exhibited impaired mitochondrial function and structure, increased lipid accumulation, and aggregated cardiac dysfunction. Conversely, T2DM mice receiving AAV9-CH25H displayed cardioprotective effects. Mechanistically, RNA sequencing and qPCR analysis revealed that CH25H deficiency decreased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target gene expression. Additionally, administration of ZLN005, a potent PGC-1α activator, partially protected against high glucose and palmitic acid induced mitochondria dysfunction and lipid accumulation in vitro. CONCLUSION: Our study provides compelling evidence supporting the protective role of CH25H in T2DM-induced cardiomyopathy. Furthermore, the regulation of PGC-1α may be intricately involved in this cardioprotective process.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Diabetic Cardiomyopathies , Mice, Knockout , Animals , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/prevention & control , Diabetic Cardiomyopathies/etiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Mice , Male , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Steroid Hydroxylases/metabolism , Steroid Hydroxylases/genetics , Diet, High-Fat/adverse effects , Mice, Inbred C57BL , Hydroxycholesterols/metabolism , Myocardium/metabolism , Myocardium/pathology , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
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