Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.129
Filter
1.
Pharmacol Res ; 205: 107236, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38797358

ABSTRACT

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.

2.
Biomed Pharmacother ; 175: 116694, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38713943

ABSTRACT

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.


Subject(s)
Atherosclerosis , Diabetes Mellitus , Kaempferols , Non-alcoholic Fatty Liver Disease , Obesity , Humans , Kaempferols/pharmacology , Kaempferols/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Obesity/drug therapy , Obesity/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Signal Transduction/drug effects
3.
Article in English | MEDLINE | ID: mdl-38740536

ABSTRACT

BACKGROUND AND AIMS: Both iron overload and iron deficiency have been associated with cardiovascular diseases in observational studies. Previous Mendelian Randomization (MR) studies discovered a protective effect of higher iron status on coronary atrial disease, while a neutral effect on all-cause heart failure. Using two-sample MR, we evaluated how genetically predicted systemic iron status affects the risk of non-ischemic cardiomyopathy and different phenotypes. METHODS AND RESULTS: Two-sample MR analyses were performed to estimate the causal effect of four biomarkers of systemic iron status on diagnosed cardiomyopathy and its subtypes in 242,607 participants from the FinnGen research project. The level of transferrin saturation was significantly associated with an increased risk of cardiomyopathy (OR, 1.17; 95% CI, 1.13-1.38) when using nine separately selected genetic instruments. An increase in genetically determined serum iron (odds ratio [OR] per standard deviation [SD], 1.25; 95% confidence interval [CI], 1.13-1.38) and ferritin (OR, 1.49; 95% CI, 1.02-2.18) were associated with an increased risk of cardiomyopathy. Total iron binding capacity, a marker of reduced iron status, was inversely linked with cardiomyopathy (OR, 0.80; 95% CI, 0.65-0.98). The risk effect of iron status was more evident in hypertrophic cardiomyopathy and related heart failure. CONCLUSIONS: These analyses support the causal effect of increased systemic iron status on a higher risk of non-ischemic cardiomyopathy. A screening test for cardiomyopathy should be considered in patients with evidence of iron overload. Future study is needed for exploring the mechanism of these causal variants on cardiomyopathy.

4.
Parasite ; 31: 23, 2024.
Article in English | MEDLINE | ID: mdl-38759153

ABSTRACT

Eimeria tenella is an obligate intracellular parasite which causes great harm to the poultry breeding industry. Protein phosphorylation plays a vital role in host cell-E. tenella interactions. However, no comprehensive phosphoproteomic analyses of host cells at various phases of E. tenella infection have been published. In this study, quantitative phosphoproteomic analysis of chicken embryo DF-1 fibroblasts that were uninfected (UI) or infected with E. tenella for 6 h (PI6, the early invasion phase) or 36 h (PI36, the trophozoite development phase) was conducted. A total of 10,122 phosphopeptides matched to 3,398 host cell phosphoproteins were identified and 13,437 phosphorylation sites were identified. Of these, 491, 1,253, and 275 differentially expressed phosphorylated proteins were identified in the PI6/UI, PI36/UI, and PI36/PI6 comparisons, respectively. KEGG pathway enrichment analysis showed that E. tenella modulated host cell processes through phosphorylation, including focal adhesion, regulation of the actin cytoskeleton, and FoxO signaling to support its early invasion phase, and modulating adherens junctions and the ErbB signaling pathway to favor its trophozoite development. These results enrich the data on the interaction between E. tenella and host cells and facilitate a better understanding of the molecular mechanisms underlying host-parasite relationships.


Title: Analyse phosphoprotéomique quantitative de cellules DF-1 de poulet infectées par Eimeria tenella, par spectrométrie de masse avec marqueur de masse en tandem (TMT) et surveillance des réactions parallèles (PRM). Abstract: Eimeria tenella est un parasite intracellulaire obligatoire qui cause de graves dommages à l'industrie de l'élevage de volailles. La phosphorylation des protéines joue un rôle essentiel dans les interactions entre la cellule hôte et E. tenella. Cependant, aucune analyse phosphoprotéomique complète des cellules hôtes à différentes phases de l'infection par E. tenella n'a été publiée. Dans cette étude, une analyse phosphoprotéomique quantitative de fibroblastes DF-1 d'embryon de poulet non infectés (NI) ou infectés par E. tenella pendant 6 h (PI6, la phase d'invasion précoce) ou 36 h (PI36, la phase de développement des trophozoïtes) a été réalisée. Un total de 10 122 phosphopeptides correspondant à 3 398 phosphoprotéines de cellules hôtes ont été identifiés et 13 437 sites de phosphorylation ont été identifiés. Parmi celles-ci, 491, 1 253 et 275 protéines différentiellement phosphorylées exprimées ont été identifiées respectivement dans les comparaisons PI6/NI, PI36/NI et PI36/PI6. L'analyse d'enrichissement de la voie KEGG a montré qu'E. tenella modulait les processus de la cellule hôte par phosphorylation, y compris l'adhésion focale, la régulation du cytosquelette d'actine et la signalisation FoxO, pour aider sa phase d'invasion précoce, et la modulation des jonctions adhérentes et de la voie de signalisation ErbB pour favoriser le développement de son trophozoïte. Ces résultats enrichissent les données sur l'interaction entre E. tenella et les cellules hôtes et facilitent une meilleure compréhension des mécanismes moléculaires sous-jacents aux relations hôtes­parasites.


Subject(s)
Chickens , Eimeria tenella , Fibroblasts , Phosphoproteins , Proteomics , Tandem Mass Spectrometry , Animals , Eimeria tenella/physiology , Chickens/parasitology , Proteomics/methods , Phosphoproteins/analysis , Phosphoproteins/metabolism , Phosphorylation , Fibroblasts/parasitology , Cell Line , Poultry Diseases/parasitology , Host-Parasite Interactions , Coccidiosis/parasitology , Coccidiosis/veterinary , Chick Embryo , Signal Transduction
5.
Bull Exp Biol Med ; 176(5): 543-547, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38717566

ABSTRACT

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC.


Subject(s)
Body Temperature , Colitis , Hemodynamics , Probiotics , Rats, Inbred SHR , Rats, Inbred WKY , Animals , Probiotics/pharmacology , Probiotics/administration & dosage , Rats , Male , Colitis/chemically induced , Colitis/physiopathology , Colitis/microbiology , Hemodynamics/drug effects , Body Temperature/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Heart Rate/drug effects , Lactobacillus delbrueckii , Obesity/physiopathology , Obesity, Abdominal/physiopathology , Obesity, Abdominal/chemically induced
6.
Vestn Oftalmol ; 140(2): 85-90, 2024.
Article in Russian | MEDLINE | ID: mdl-38742503

ABSTRACT

The introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts. The described methods of treatment, according to the authors, are the most promising.


Subject(s)
Keratoconus , Keratoconus/surgery , Keratoconus/diagnosis , Humans , Cornea/surgery , Cornea/diagnostic imaging , Corneal Transplantation/methods , Corneal Surgery, Laser/methods , Treatment Outcome , Collagen
7.
Int J Ophthalmol ; 17(5): 852-860, 2024.
Article in English | MEDLINE | ID: mdl-38766337

ABSTRACT

AIM: To assess the performance of macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and 10-2 visual field (VF) parameters in detecting early glaucoma and evaluating the severity of advanced glaucoma. METHODS: Totally 127 eyes from 89 participants (36 eyes of 19 healthy participants, 45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients) were included. The relationships between the optical coherence tomography (OCT)-derived parameters and VF sensitivity were determined. Patients with early glaucoma were divided into eyes with or without central 10° of the VF damages (CVFDs), and the diagnostic performances of OCT-derived parameters were assessed. RESULTS: In early glaucoma, the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation (PSD; with average mGCIPLT: ß=-0.046, 95%CI, -0.067 to -0.024, P<0.001). In advanced glaucoma, the mGCIPLT was related to the 24-2 VF mean deviation (MD; with average mGCIPLT: ß=0.397, 95%CI, 0.199 to 0.595, P<0.001), 10-2 VF MD (with average mGCIPLT: ß=0.762, 95%CI, 0.485 to 1.038, P<0.001) and 24-2 VF PSD (with average mGCIPLT: ß=0.244, 95%CI, 0.124 to 0.364, P<0.001). Except for the minimum and superotemporal mGCIPLT, the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without CVFDs. The area under the curve (AUC) of the average mGCIPLT (AUC=0.949, 95%CI, 0.868 to 0.982) was greater than that of the average circumpapillary retinal nerve fiber layer thickness (cpRNFLT; AUC=0.827, 95%CI, 0.674 to 0.918) and rim area (AUC=0.799, 95%CI, 0.610 to 0.907) in early glaucomatous eyes with CVFDs versus normal eyes. CONCLUSION: The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF, cpRNFLT and ONH parameters, especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

8.
Biomedicines ; 12(5)2024 May 07.
Article in English | MEDLINE | ID: mdl-38790992

ABSTRACT

The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.

9.
Int J Mol Sci ; 25(10)2024 May 19.
Article in English | MEDLINE | ID: mdl-38791584

ABSTRACT

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene expression profiling identified significantly different neuregulin-2 gene (NRG2) expression between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23 ± 2.80) was significantly lower than that in the controls (9.27 ± 4.78, p < 0.001). Next, we conducted resequencing of all the exons of NRG2 in a sample of 349 individuals with ASD, aiming to identify variants of the NRG2 associated with ASD. We identified three variants, including two single nucleotide variants (SNVs), IVS3 + 13A > G (rs889022) and IVS10 + 32T > A (rs182642591), and one small deletion at exon 11 of NRG2 (delGCCCGG, rs933769137). Using data from the Taiwan Biobank as the controls, we found no significant differences in allele frequencies of rs889022 and rs182642591 between two groups. However, there is a significant difference in the genotype and allele frequency distribution of rs933769137 between ASDs and controls (p < 0.0001). The small deletion is located in the EGF-like domain at the C-terminal of the NRG2 precursor protein. Our findings suggest that NRG2 might be a susceptibility gene for ASD.


Subject(s)
Autism Spectrum Disorder , Genetic Predisposition to Disease , Neuregulins , Polymorphism, Single Nucleotide , Humans , Autism Spectrum Disorder/genetics , Male , Female , Neuregulins/genetics , Neuregulins/metabolism , Gene Frequency , Case-Control Studies , Child , Genetic Association Studies , Gene Expression Profiling , Exons/genetics , Adolescent , Adult , Nerve Growth Factors
10.
Heart ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38729636

ABSTRACT

OBJECTIVE: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone. METHODS: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform. RESULTS: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio. CONCLUSIONS: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs. TRIAL REGISTRATION NUMBER: NCT02556450.

11.
Sci Justice ; 64(3): 269-278, 2024 May.
Article in English | MEDLINE | ID: mdl-38735662

ABSTRACT

A novel technique is introduced to predict the printer model used to produce a given document. Samples containing only a few letters printed under varying conditions (i.e., different printing modes, letter types, fonts) were collected to establish a dataset of 41 inkjet printer models from common manufacturers, such as HP, Canon, and Epson. Morphological features were analyzed by extraction of image features using several algorithms in a series of microscopic images and a Wilcoxon test was used to measure the significance of variations between printed samples. Significant differences between various printing conditions might post potential challenge to questioned document examination. Discriminant analysis and the k-nearest neighbor (KNN) algorithm were also employed for source printer prediction under varying printing condition on 30% images with the rest images as training dataset. The results of a validation experiment demonstrated that while quadratic discriminant analysis (QDA) achieved an accuracy of 96.3%, a combination of KNN and QDA reached 98.6%. As such, this technique could aid in the forensic examination of printed documents.

12.
NPJ Parkinsons Dis ; 10(1): 100, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730245

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a common comorbidity among Parkinson's disease (PD) patients. Yet, little is known about dysregulated pathways that are unique in PD patients with T2DM. We applied high-resolution metabolomic profiling in serum samples of 636 PD and 253 non-PD participants recruited from Central California. We conducted an initial discovery metabolome-wide association and pathway enrichment analysis. After adjusting for multiple testing, in positive (or negative) ion mode, 30 (25) metabolic features were associated with T2DM in both PD and non-PD participants, 162 (108) only in PD participants, and 32 (7) only in non-PD participants. Pathway enrichment analysis identified 17 enriched pathways associated with T2DM in both the PD and non-PD participants, 26 pathways only in PD participants, and 5 pathways only in non-PD participants. Several amino acid, nucleic acids, and fatty acid metabolisms were associated with T2DM only in the PD patient group suggesting a possible link between PD and T2DM.

13.
J Mater Chem B ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727406

ABSTRACT

Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials.

14.
Chem Pharm Bull (Tokyo) ; 72(5): 507-511, 2024.
Article in English | MEDLINE | ID: mdl-38811194

ABSTRACT

Amaryllidaceae alkaloids are structurally diverse natural products with a wide range biological properties, and based on the partial identification of the biosynthetic enzymes, norbelladine would be a common intermediate in the biosynthetic pathways. Previous studies suggested that norbelladine synthase (NBS) catalyzed the condensation reaction of 3,4-dihydroxybenzaldehyde and tyramine to form norcraugsodine, and subsequently, noroxomaritidine/norcraugsodine reductase (NR) catalyzed the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of norcraugsodine to generate norbelladine. However, recent studies have highlighted possible alternative Amaryllidaceae alkaloid biosynthetic pathways via the formation of isovanillin and vanillin from the 4-O- and 3-O-methylation reactions of 3,4-dihydroxybenzaldehyde, respectively. Herein, we focused on NpsNBS and NpsNR, which were initially identified from Narcissus pseudonarcissus, and explored their substrate recognition tolerance by performing condensation reactions of tyramine with various benzaldehyde derivatives, to shed light on the Amaryllidaceae alkaloid biosynthetic pathway from the viewpoint of the enzymatic properties. The assays revealed that both NpsNBS and NpsNR lacked the abilities to produce 4'-O- and 3'-O-methylnorbelladine from isovanillin and vanillin with tyramine, respectively. These observations thus suggested that Amaryllidaceae alkaloids are biosynthesized from norbelladine, formed through the condensation/reduction reaction of 3,4-dihydroxybenzaldehyde with tyramine.


Subject(s)
Aldehydes , Aldehydes/chemistry , Aldehydes/metabolism , Hydroxylation , Molecular Structure , Substrate Specificity , Nitrate Reductase/chemistry , Nitrate Reductase/metabolism
15.
Med Sci Sports Exerc ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38768014

ABSTRACT

PURPOSE: Chronic, high-altitude hypoxic exposure increases the risk of high-altitude pulmonary hypertension (PH). Emerging evidence shows maternal exercise may improve offspring resistance to disease throughout life. The purpose of this study is to determine if maternal exercise mitigates chronic hypoxic-induced changes in the offspring indicative of high-altitude pulmonary hypertension development. METHODS: Female adult C57BL/6 J mice were randomly allocated to nonexercise or exercise conditions. Exercise consisted of voluntary running wheel exercise for four weeks during the perinatal period. Three days after birth, the pups remained at low altitude (normoxia) or were exposed to hypobaric hypoxia of 450 mmHg to simulate ~4500 m altitude exposure until 8 weeks of age. The study consisted of 4 groups: Hypoxia + Nonexercise pregnancy, Hypoxia + Exercise, or the respective, normoxia conditions (Normoxia + Nonexercise or Normoxia + Exercise). Offspring body size, motor function, right ventricular systolic pressure (RVSP), and cardiopulmonary morphology were assessed after 8 weeks in normoxia or hypoxia. RESULTS: Both hypoxic groups had smaller body sizes, reduced motor function, increased hematocrit, RVSP, muscularization in medium-sized pulmonary arteries, as well as right ventricular hypertrophy and contractility compared to the normoxic groups ( p < 0.05). CONCLUSIONS: Chronic hypoxia simulating 4500 m attenuated growth, lowered motor function, and elicited PH development. Voluntary maternal exercise did not significantly decrease RVSP in the offspring, which aligned with a lack of effect to attenuate abnormal body size and cardiopulmonary development due to chronic hypoxia. These findings are preliminary in nature and more powered studies through larger group sizes are required to generalize the results to the population.

16.
J Hazard Mater ; 472: 134498, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38733782

ABSTRACT

Advanced oxidation processes for the treatment of organic pollutants in wastewater suffer from difficulties in mineralization, potential risks of dissolved residues, and high oxidant consumption. In this study, radical-initiated polymerization is dominated in an UV/peroxydisulfate (PDS) process to eliminate organic pollutant of pharmaceutical metoprolol (MTP). Compared with an ideal degradation-based UV/PDS process, the present process can save four fifths of PDS consumption at the same dissolved organic carbon removal of 47.3%. Simultaneously, organic carbon can be recovered from aqueous solution by separating solid polymers at a ratio of 50% of the initial chemical oxygen demand. The chemical structure of products was analyzed to infer the transformation pathways of MTP. Unlike previous studies on simple organic pollutants that the polymerization can occur independently, the polymerization of MTP is dependent on the partial degradation of MTP, and the main monomer in polymerization is a dominant degradation product (4-(2-methoxyethyl)-phenol, denoted as DP151). The separated solid polymers are formed by repeated oxidation and coupling of DP151 or its derivatives through a series of intermediate oligomers. This proof-of-concept study demonstrates the advantage of polymerization-dominated mechanism on dealing with large organic molecules with complex structures, as well as the potential of UV/PDS process for simultaneous organic pollution reduction and organic carbon recovery from aqueous solution.

17.
Sci Data ; 11(1): 467, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719891

ABSTRACT

Angiogenesis is extensively involved in embryonic development and requires complex regulation networks, whose defects can cause a variety of vascular abnormalities. Cis-regulatory elements control gene expression at all developmental stages, but they have not been studied or profiled in angiogenesis yet. In this study, we exploited public DNase-seq and RNA-seq datasets from a VEGFA-stimulated in vitro angiogenic model, and carried out an integrated analysis of the transcriptome and chromatin accessibility across the entire process. Totally, we generated a bank of 47,125 angiogenic cis-regulatory elements with promoter (marker by H3K4me3) and/or enhancer (marker by H3K27ac) activities. Motif enrichment analysis revealed that these angiogenic cis-regulatory elements interacted preferentially with ETS family TFs. With this tool, we performed an association study using our WES data of TAPVC and identified rs199530718 as a cis-regulatory SNP associated with disease risk. Altogether, this study generated a genome-wide bank of angiogenic cis-regulatory elements and illustrated its utility in identifying novel cis-regulatory SNPs for TAPVC, expanding new horizons of angiogenesis as well as vascular abnormality genetics.


Subject(s)
Polymorphism, Single Nucleotide , Humans , Regulatory Sequences, Nucleic Acid , Vascular Endothelial Growth Factor A/genetics , Genome-Wide Association Study , Neovascularization, Pathologic/genetics
18.
Nanoscale ; 16(20): 9770-9780, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38597919

ABSTRACT

Prussian blue nanoparticles exhibit the potential to be employed in bioanalytical applications due to their robust stability, peroxidase-like catalytic functionality, straightforward synthesis, and biocompatibility. An efficient approach is presented for the synthesis of nucleic acid-modified Prussian blue nanoparticles (DNA-PBNPs), utilizing nanoparticle porosity to adsorb nucleic acids (polyT). This strategic adsorption leads to the exposure of nucleic acid sequences on the particle surface while retaining catalytic activity. DNA-PBNPs further couple with functional nucleic acid sequences and aptamers through complementary base pairing to act as transducers in biosensors and amplify signal acquisition. Subsequently, we integrated a copper ion-dependent DNAzyme (Cu2+-DNAzyme) and a vascular endothelial growth factor aptamer (VEGF aptamer) onto screen-printed electrodes to serve as recognition elements for analytes. Significantly, our approach leverages DNA-PBNPs as a superior alternative to traditional enzyme-linked antibodies in electrochemical biosensors, thereby enhancing both the efficiency and adaptability of these devices. Our study conclusively demonstrates the application of DNA-PBNPs in two different biosensing paradigms: the sensitive detection of copper ions and vascular endothelial growth factor (VEGF). These results indicate the promising potential of DNA-modified Prussian blue nanoparticles in advancing bioanalytical sensing technologies.


Subject(s)
Biosensing Techniques , Copper , DNA, Catalytic , DNA , Electrochemical Techniques , Ferrocyanides , Vascular Endothelial Growth Factor A , Ferrocyanides/chemistry , Biosensing Techniques/methods , DNA, Catalytic/chemistry , Vascular Endothelial Growth Factor A/analysis , Copper/chemistry , DNA/chemistry , Aptamers, Nucleotide/chemistry , Nanoparticles/chemistry , Humans , Electrodes
19.
J Cancer Res Ther ; 20(2): 599-607, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38687930

ABSTRACT

OBJECTIVE: It is crucially essential to differentially diagnose single-nodule pulmonary metastases (SNPMs) and second primary lung cancer (SPLC) in patients with colorectal cancer (CRC), which has important clinical implications for treatment strategies. In this study, we aimed to establish a feasible differential diagnosis model by combining 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) radiomics, computed tomography (CT) radiomics, and clinical features. MATERIALS AND METHODS: CRC patients with SNPM or SPLC who underwent 18F-FDG PET/CT from January 2013 to July 2022 were enrolled in this retrospective study. The radiomic features were extracted by manually outlining the lesions on PET/CT images, and the radiomic modeling was realized by various screening methods and classifiers. In addition, clinical features were analyzed by univariate analysis and logistic regression (LR) analysis to be included in the combined model. Finally, the diagnostic performances of these models were illustrated by the receiver operating characteristic (ROC) curves and the area under the curve (AUC). RESULTS: We studied data from 61 patients, including 36 SNPMs and 25 SPLCs, with an average age of 65.56 ± 10.355 years. Spicule sign and ground-glass opacity (GGO) were significant independent predictors of clinical features (P = 0.012 and P < 0.001, respectively) to build the clinical model. We achieved a PET radiomic model (AUC = 0.789), a CT radiomic model (AUC = 0.818), and a PET/CT radiomic model (AUC = 0.900). The PET/CT radiomic models were combined with the clinical model, and a well-performing model was established by LR analysis (AUC = 0.940). CONCLUSIONS: For CRC patients, the radiomic models we developed had good performance for the differential diagnosis of SNPM and SPLC. The combination of radiomic and clinical features had better diagnostic value than a single model.


Subject(s)
Colorectal Neoplasms , Fluorodeoxyglucose F18 , Lung Neoplasms , Positron Emission Tomography Computed Tomography , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Female , Diagnosis, Differential , Middle Aged , Aged , Retrospective Studies , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/diagnosis , ROC Curve , Radiopharmaceuticals , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/pathology , Adult , Radiomics
20.
Int J Cardiol ; 407: 132064, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38670460

ABSTRACT

PURPOSE: Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). METHODS: Patients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. RESULTS: Totally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52-67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04-1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93-0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95-0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). CONCLUSION: Higher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Nutrition Assessment , Nutritional Status , Humans , Cardiac Resynchronization Therapy/methods , Cardiac Resynchronization Therapy/trends , Male , Female , Aged , Middle Aged , Retrospective Studies , Heart Failure/therapy , Heart Failure/mortality , Heart Failure/physiopathology , Heart Failure/diagnosis , Prognosis , Nutritional Status/physiology , Treatment Outcome , Geriatric Assessment/methods , Follow-Up Studies , Time Factors , Risk Assessment/methods , Risk Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...