Targeted delivery of activatable 131I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics.

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in several types of human cancers, we have reported a 131I-labeled radiopharmaceutical ([131I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) for treatment of legumain-overexpressed tumors in vivo. However, liver enrichment limits its application. In this study, a new radiopharmaceutical [131I]IM(HE)3AAN was synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE)3) into [131I]MAAN to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic [131I]IM(HE)3AAN could react with its precursor to form heterologous dimer ([131I]H-Dimer) that is highly hydrophobic. Cerenkov imaging reveals that [131I]IM(HE)3AAN displayed superior tumor selectivity and longer tumor retention time as compared with [131I]MAAN, with a significant reduction in liver uptake. After an 18-day treatment with [131I]IM(HE)3AAN, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs during treatment. These findings suggest [131I]IM(HE)3AAN emerges as a promising candidate for treatment of legumain-overexpressed tumors.

Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.

BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD. METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association. RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.

Pioglitazone Alleviates ß1-Adrenergic Receptor Antibody-Induced Atrial Fibrillation Susceptivity via Mitigation of PPAR-γ-Mediated Metabolic Inflexibility.

BACKGROUND: Beta-1-adrenergic receptor antibodies (ß1-AAbs) function as arrhythmogenic molecules in autoimmune-related atrial fibrillation (AF). This study examined the potential impact of pioglitazone, an agonist for peroxisome proliferator-activated receptor-γ (PPAR-γ), on atrial remodeling induced by ß1-AAbs. METHODS: An in vivo study was performed to confirm the protective effects of pioglitazone on ß1- AAbs-induced atrial remodeling. GW9662, a PPAR-γ antagonist, was employed to identify the potential therapeutic target of pioglitazone. The rats were administered subcutaneous injections of the second extracellular loop peptide for 8 weeks to establish active immunization models. Pioglitazone was then administered orally for 2 weeks. Epicardial electrophysiologic studies, multielectrode array measurements, and echocardiography were conducted to examine atrial remodeling. Glucose metabolism products and key metabolic molecules were measured to evaluate the atrial substrate metabolism. Mitochondrial morphologies and function indices were tested to depict the underlying links between atrial metabolism and mitochondrial homeostasis under the pioglitazone treatment. RESULTS: Pioglitazone significantly reversed ß1-AAbs-induced AF susceptibility, ameliorated atrial structural remodeling, decreased the global insulin resistance reflected in the plasma glucose and insulin levels, and increased the protein expressions of glycolipid uptake and transportation (GLUT1, CD36, and CPT1a). These trends were counterbalanced by the GW9662 intervention. Mechanistically, pioglitazone mitigated the atrial mitochondrial network damage and partly renovated the mitochondrial biogenesis, even the mitochondrial dynamics, which were reversed by inhibiting the PPAR-γ target. CONCLUSION: Pioglitazone effectively reduced the AF vulnerability and recovered the atrial myocardial metabolism and mitochondrial damage. The potential anti-remodeling effect of pioglitazone on the atrium was associated with the moderately increased expression of key membrane proteins related to glucose transporter and fatty acid uptake, which may promote the increased myocardial preference for utilization of FA as the key cardiac oxidative fuel and ameliorate the atrial metabolic inflexibility.

ADPN Regulates Oxidative Stress-Induced Follicular Atresia in Geese by Modulating Granulosa Cell Apoptosis and Autophagy.

Geese are susceptible to oxidative stress during reproduction, which can lead to follicular atresia and impact egg production. Follicular atresia is directly triggered by the apoptosis and autophagy of granulosa cells (GCs). Adiponectin (ADPN), which is secreted by adipose tissue, has good antioxidant and anti-apoptotic capacity, but its role in regulating the apoptosis of GCs in geese is unclear. To investigate this, this study examined the levels of oxidative stress, apoptosis, and autophagy in follicular tissues and GCs using RT-qPCR, Western blotting, immunofluorescence, flow cytometry, transcriptomics and other methods. Atretic follicles exhibited high levels of oxidative stress and apoptosis, and autophagic flux was obstructed. Stimulating GCs with H2O2 produced results similar to those of atretic follicles. The effects of ADPN overexpression and knockdown on oxidative stress, apoptosis and autophagy in GCs were investigated. ADPN was found to modulate autophagy and reduced oxidative stress and apoptosis in GCs, in addition to protecting them from H2O2-induced damage. These results may provide a reasonable reference for improving egg-laying performance of geese.

Dialdehyde cellulose (DAC) and polyethyleneimine (PEI) coated polyvinylidene fluoride (PVDF) membrane for simultaneously removing emulsified oils and anionic dyes.

Developing high-efficiency membrane for oil and dye removal is very urgent, because wastewater containing them can cause great damage to human and environment. In this study, a coated membrane was fabricated by applying DAC and PEI onto the commercial PVDF microfiltration membrane for supplying the demand. The coated membrane presents superhydrophlic and superoleophobic properties with a water contact angle of 0o and underwater oil contact angle exceed 150°, as well as excellent low underwater oil adhesion performance. The coated membrane shows high separation efficiency exceeded 99.0% and flux 350.0 L·m-2·h-1 when used for separating for six kinds of oil including pump oil, sunflower oil, n-hexadecane, soybean oil, diesel and kerosene in water emulsions. Additionally, the coated membrane can effectively remove anionic dyes, achieving rejection rates of 94.7%, 93.4%, 92.3%, 90.7% for the CR, MB, RB5, AR66, respectively. More importantly, the membrane was able to simultaneously remove emulsified oil and soluble anionic dyes in wastewater containing both of them. Therefore, this novel coated membrane can be a promising candidate for treating complex wastewater.

Legumain-Triggered Macrocyclization of Radiofluorinated Tracer for Enhanced PET Imaging.

Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an 18F-labeled radiotracer [18F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([18F]AlF-RESCA) method with high radiochemical yield (RCY) (88.35 ± 3.93%) and radiochemical purity (RCP) (>95%). More notably, the tracer can be transformed into a hydrophobic macrocyclic molecule under the joint action of legumain and reductant. Simultaneously, the tracer could target legumain-positive tumors and enhance accumulation and retention in tumors, resulting in the amplification of PET imaging signals. The enhancement of radioactivity enables PET imaging of legumain activity with high specificity. We envision that, by combining this highly efficient 18F-labeled strategy with our intramolecular macrocyclization reaction, a range of radiofluorinated tracers can be designed for tumor PET imaging and early cancer diagnosis in the future.

Choline Dehydrogenase Contributes to Salt Tolerance in Dunaliella through Betaine Synthesis.

In Dunaliella tertiolecta, a microalga renowned for its extraordinary tolerance to high salinity levels up to 4.5 M NaCl, the mechanisms underlying its stress response have largely remained a mystery. In a groundbreaking discovery, this study identifies a choline dehydrogenase enzyme, termed DtCHDH, capable of converting choline to betaine aldehyde. Remarkably, this is the first identification of such an enzyme not just in D. tertiolecta but across the entire Chlorophyta. A 3D model of DtCHDH was constructed, and molecular docking with choline was performed, revealing a potential binding site for the substrate. The enzyme was heterologously expressed in E. coli Rosetta (DE3) and subsequently purified, achieving enzyme activity of 672.2 U/mg. To elucidate the role of DtCHDH in the salt tolerance of D. tertiolecta, RNAi was employed to knock down DtCHDH gene expression. The results indicated that the Ri-12 strain exhibited compromised growth under both high and low salt conditions, along with consistent levels of DtCHDH gene expression and betaine content. Additionally, fatty acid analysis indicated that DtCHDH might also be a FAPs enzyme, catalyzing reactions with decarboxylase activity. This study not only illuminates the role of choline metabolism in D. tertiolecta's adaptation to high salinity but also identifies a novel target for enhancing the NaCl tolerance of microalgae in biotechnological applications.

OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/ß-Catenin Signaling Pathways.

Spinal cord injury (SCI) is a significant health concern, as it presently has no effective treatment in the clinical setting. Inflammation is a key player in the pathophysiological process of SCI, with a number of studies evidencing that the inhibition of the NF-κB signaling pathway may impede the inflammatory response and improve SCI. OTULIN, as a de-ubiquitination enzyme, the most notable is its anti-inflammatory effect. OTULIN can inhibit the NF-κB signaling pathway to suppress the inflammatory reaction via de-ubiquitination. In addition, OTULIN may promote vascular regeneration through the Wnt/ß-catenin pathway in the wake of SCI. In this review, we analyze the structure and physiological function of OTULIN, along with both NF-κB and Wnt/ß-catenin signaling pathways. Furthermore, we examine the significant role of OTULIN in SCI through its impairment of the NF-κB signaling pathway, which could open the possibility of it being a novel interventional target for the condition.

Rutaecarpine protects podocytes in diabetic kidney disease by targeting VEGFR2/NLRP3-mediated pyroptosis.

OBJECTIVE: Diabetic kidney disease (DKD) is the most common cause of the end-stage renal disease, which has limited treatment options. Rutaecarpine has anti-inflammatory effects, however, it has not been studied in DKD. Pyroptosis is a newly discovered mode of podocyte death related to inflammation. This study aimed to explore whether Rutaecarpine can ameliorate DKD and to clarify its possible mechanism. METHODS: In this study, we investigated the effects of Rutaecarpine on DKD using diabetic mice model (db/db mice) and high glucose (HG)-stimulated mouse podocyte clone 5 (MPC5) cells. Quantitative reverse transcription polymerase chain reaction and western blot were performed to detect the related gene and protein levels. We applied pharmacological prediction, co-immunoprecipitation assay, cellular thermal shift assay, surface plasmon resonance to find the target and pathway of the substances. Gene knockdown experiments confirmed this view in HG-stimulated MPC5 cells. RESULTS: Rutaecarpine significantly reduced proteinuria, histopathological damage, and pyroptosis of podocytes in a dose-dependent manner in db/db mice. Rutaecarpine also protected high glucose induced MPC5 injury in vitro experiments. Mechanistically, Rutaecarpine can inhibit pyroptosis in HG-stimulated MPC5 by reducing the expression of VEGFR2. VEGFR2 is a target of Rutaecarpine in MPC5 cells and directly binds to the pyroptosis initiation signal, NLRP3. VEGFR2-knockdown disrupted the beneficial effects of Rutaecarpine in HG-stimulated MPC5 cells. CONCLUSION: Rutaecarpine inhibits renal inflammation and pyroptosis through VEGFR2/NLRP3 pathway, thereby alleviating glomerular podocyte injury. These findings highlight the potential of Rutaecarpine as a novel drug for DKD treatment.

New Design Method of a Supersonic Steam Injection Nozzle and Its Numerical Simulation Verification.

Steam huff-n-puff in horizontal wells often had limitations, such as uneven steam injection and low reservoir utilization. To improve steam injection efficiency, a new method for designing a supersonic nozzle was proposed based on the principles of aerodynamics and thermodynamics. The nozzle featured a tapering section, a throat, and a diverging section. The best geometric shape of the tapering section was the Witoszynski curve. A set of nozzle size designs were established, and the size parameters were optimized. The results showed that the nozzle could inject steam into the formation at supersonic speed and it had the characteristics of constant flow rate and uniform development of the steam chamber. According to the steam Reynolds number and the good aggregation distribution characteristics of the size design model, three sequential nozzles of 3.0, 5.0, and 6.5 mm were formed based on the throat. When the throat diameter was 5.0 mm, the tapering length was 4.3 mm, the diverging length was 5.5 mm, the throat length was 3.0 mm, the inlet diameter was 9.8 mm, and the outlet diameter was 6.2 mm. Numerical simulations indicated that the pressure drop loss during steam huff-n-puff injection in horizontal wells was within 10%. It was of great significance to establish the nozzle size design model of the steam injection effect of horizontal wells.

Two Birds with One Stone: A Novel Dithiomaleimide-Based GalNAc-siRNA Conjugate Enabling Good siRNA Delivery and Traceability.

For the first time, a novel dithiomaleimides (DTM) based tetra-antennary GalNAc conjugate was developed, which enable both efficient siRNA delivery and good traceability, without incorporating extra fluorophores. This conjugate can be readily constructed by three click-type reactions, that is, amidations, thiol-dibromomaleimide addition and copper catalyzed azide-alkyne cycloaddition (CuAAC). And it also has comparable siRNA delivery efficiency, with a GalNAc L96 standard to mTTR target. Additionally, due to the internal DTMs, a highly fluorescent emission was observed, which benefited delivery tracking and reduced the cost and side effects of the extra addition of hydrophobic dye molecules. In all, the simple incorporation of DTMs to the GalNAc conjugate structure has potential in gene therapy and tracking applications.

Single cell characteristics of patients with vaccine-related adverse reactions following inactivated COVID-19 vaccination.

A good safety and immunogenicity profile was reported in Phase I and II clinical trials of inactivated SARS-CoV-2 vaccines. Here, we report two cases associated with vaccine-associated adverse events, including one patient with fever and another with anaphylactic shock resulting from inactivated SARS-CoV-2 vaccination. Cell sub-types and the importance of genetic characteristics were assessed using single-cell mRNA sequencing and machine learning. Overall, the patient with fever showed a significant increase in the numbers of cytotoxic CD8 T cells and MKI67high CD8 T cells. A potential concurrent infection with the Epstein-Barr virus enhanced interferon type I responses to vaccination against the virus. STAT1, E2F1, YBX1, and E2F7 played a key role in the transcription regulation of MKI67high CD8 T cells. In contrast, the patient with allergic shock displayed predominant increases in the numbers of S100A9high monocytes, activated CD4 T cells, and PPBPhigh megakaryocytes. The decision tree showed that LYZ and S100A8 in S100A9high monocytes contributed to the degranulation of neutrophils and activation of neutrophils involved in allergic shock. PPBP and PF4 were major contributors to platelet degranulation. These findings highlight the diversity of adverse reactions following inactivated SARS-CoV-2 vaccination and show the emerging role of cellular subtypes and central genes in vaccine-associated adverse reactions.

The identification of cell sub-types may help in the diagnosis of COVID-19 vaccine-related adverse events.COVID-19 vaccination-related acute pulmonary edema may induce a higher risk of thrombosis.The long-term fever after vaccination may attribute to the excessive type I interferon responses.

Molecular dynamics simulations reveal the inhibition mechanism of Cdc42 by RhoGDI1.

Cell division control protein 42 homolog (Cdc42), which controls a variety of cellular functions including rearrangements of the cell cytoskeleton, cell differentiation and proliferation, is a potential cancer therapeutic target. As an endogenous negative regulator of Cdc42, the Rho GDP dissociation inhibitor 1 (RhoGDI1) can prevent the GDP/GTP exchange of Cdc42 to maintain Cdc42 into an inactive state. To investigate the inhibition mechanism of Cdc42 through RhoGDI1 at the atomic level, we performed molecular dynamics (MD) simulations. Without RhoGDI1, Cdc42 has more flexible conformations, especially in switch regions which are vital for binding GDP/GTP and regulators. In the presence of RhoGDI1, it not only can change the intramolecular interactions of Cdc42 but also can maintain the switch regions into a closed conformation through extensive interactions with Cdc42. These results which are consistent with findings of biochemical and mutational studies provide deep structural insights into the inhibition mechanisms of Cdc42 by RhoGDI1. These findings are beneficial for the development of novel therapies targeting Cdc42-related cancers.

Maternal supplementation with human milk-derived Lactiplantibacillus plantarum WLPL04 affects the immunity and gut microbiota of offspring rats.

Pregnancy and lactation are a window period during which interventions on mothers bring beneficial effects to newborns. This study aims to investigate the effects of maternal supplementation with human-milk-derived Lactiplantibacillus plantarum WLPL04-36e during pregnancy and lactation on the physiology, immunity and gut microbiota of dams and their offspring. We found that after maternal supplementation, L. plantarum WLPL04-36e could be detected in the intestines and extraintestinal tissues (liver, spleen, kidneys, mammary gland, MLN and brain) of dams, as well as in the intestines of their offspring. Maternal supplementation with L. plantarum WLPL04-36e could significantly increase the body weights of dams and their offspring during the middle to late lactation period, elevate the serum levels of IL-4, IL-6, and IL-10 of dams and IL-6 level of offspring, and increase the proportion of spleen CD4+ T lymphocytes of the offspring. Moreover, L. plantarum WLPL04-36e supplementation could increase the alpha diversity of milk microbiota during early and middle lactation periods, and elevated the abundance of Bacteroides in the intestines of offspring at week 2 and week 3 after birth. These results suggest that maternal supplementation with human-milk-derived L. plantarum can regulate the immunity and intestinal microbiota composition of offspring and play positive roles in the growth of offspring.

Study on Hydrothermal Cracking of Heavy Oil under the Coexisting Conditions of Supercritical Water and Non-condensate Gas.

This study looked at the effects of temperature, water-oil ratio, and the addition of non-condensable gas on the thermal cracking of extra-heavy oil in the lab. The goal was to learn more about the properties and reaction rates of deep extra-heavy oil under supercritical water conditions, which are not well understood. The changes in the composition of the extra-heavy oil were analyzed with and without the presence of non-condensable gas. The reaction kinetics of the thermal cracking of extra-heavy oil were quantitatively characterized and compared between the two conditions of supercritical water alone and supercritical water mixed with non-condensable gas. The results showed that (1) under supercritical water conditions, the extra-heavy oil underwent significant thermal cracking, which led to a significant increase in the amount of light components, the release of CH4, and the formation of a new component, coke, which led to a noticeable decrease in the viscosity of the oil; (2) increasing the water-oil ratio could promote the thermal cracking of extra-heavy oil and led to a significant decrease in oil viscosity, indicating a more complete thermal cracking reaction. Moreover, increasing the water-oil ratio was found to facilitate the flowability of the cracked oil; (3) the addition of non-condensable gas intensified the conversion of coke but inhibited and slowed down the thermal cracking of asphaltene, which is detrimental to the thermal cracking of extra-heavy oil; and (4) the kinetic analysis showed that the addition of non-condensable gas resulted in a decrease in the thermal cracking rate of asphaltene, which is detrimental to the thermal cracking of heavy oil.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.

Leaching of heavy metal(loid)s from historical Pb-Zn mining tailing in abandoned tailing deposit: Up-flow column and batch tests.

This study aims to investigate the water-leaching characteristics of heavy metal(loid)s (HMs) from historical Pb-Zn mine tailing of an abandoned tailing deposit in eastern China. Up-flow column and batch leaching tests were conducted at different liquid-to-solid (L/S) ratios to estimate the releases of HMs and investigate the controlling mechanisms. Calcite and silicate were the dominant minerals in the tailing and the HMs contents followed the order of Zn (2371 mg/kg) > Pb (2061 mg/kg) > Cu (109 mg/kg) > Cr (47.8 mg/kg) > As (15.9 mg/kg) > Cd (5.1 mg/kg). Moreover, considerable fractions of Pb, Zn, and Cd existed in the acid-soluble forms (41-47%). Column and batch leaching tests consistently showed that limited quantities (<0.002%) of HMs could be leached from this historical tailing. In particular, variations in column conditions (e.g., length, flow rate, and initial saturation) significantly affected the release fluxes from the columns but had a relatively limited effect on the leaching mechanisms. The estimated results of HM release suggested that the leaching process was predominantly solubility-controlled and the dissolution of Ca-bearing minerals (e.g., calcite) primarily controlled the release of HMs. The studied tailing had a limited impact on the quality of the surrounding aquatic environments because the water-leaching concentrations of HMs were generally lower than the Chinese standards for drinking water. Only for Pb, the leaching results in column tests were significantly lower than those in batch tests; whereas the results in column tests for other HMs were comparable to those in batch tests to a certain extent. Based on the column test results, the amounts of HMs potentially released from the abandoned tailing deposit (height, 10 m; footprint area, 30,000 m2; tailing dry density, 1.9 × 103 kg/m3) followed a decreasing order of Zn (4.2 × 105 kg) > Cu (2.3 × 104 kg) > Pb (1.4 × 104 kg) > Cr (2.3 × 104 kg) > Cd (1.6 × 103 kg) > As (1.2 × 103 kg) over the 75-year assessment period (corresponding to an L/S ratio of 10 L/kg with an annual precipitation of 1500 mm).

Ellagic acid activates the Keap1-Nrf2-ARE signaling pathway in improving Parkinson's disease: A review.

Parkinson's disease (PD) is a familiar neurodegenerative disease, accompanied by motor retardation, static tremor, memory decline and dementia. Heredity, environment, age and oxidative stress have been suggested as key factors in the instigation of PD. The Keap1-Nrf2-ARE signaling is one of the most significant anti- oxidative stress (OS) pathways. The Keap1 is a negative regulator of the Nrf2. The Keap1-Nrf2-ARE pathway can induce cell oxidation resistance and reduce nerve injury to treat neurodegenerative diseases. Ellagic acid (EA) can inhibit the Keap1 to accumulate the Nrf2 in the nucleus, and act on the ARE to produce target proteins, which in turn may alleviate the impact of OS on neuronal cells of PD. This review analyzes the structure and physiological role of EA, along with the structure, composition and functions of the Keap1-Nrf2-ARE signaling pathway. We further expound on the mechanism of ellagic acid in its activation of the Keap1-Nrf2-ARE signaling pathway, as well as the relationship between EA in impairing the TLR4/Myd88/NF-κB and Nrf2 pathways. Ellagic acid has the potentiality of improving PD by activating the Keap1-Nrf2-ARE signaling pathway and scavenging free radicals.

Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. OBJECTIVE: The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. METHODS: A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. RESULTS: Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF. CONCLUSIONS: Plasma Gal-3 concentration is an independent predictor of post-MI NOAF.