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1.
Tree Physiol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976033

ABSTRACT

Mangroves perform a crucial ecological role along the tropical and subtropical coastal intertidal zone where salinity fluctuation is frequently happened. However, the differential responses of mangrove plant at transcriptome combined metabolome level to variable salinity are not well documented. In this study, we used Avicennia marina, a pioneer species of mangrove wetlands and one of the most salt-tolerant mangroves, to investigate the differential salt tolerance mechanisms under low and high salinity using ICP-MS, transcriptomic and metabolomic analysis. The results showed that HAK8 was up-regulated and transported K+ into the roots under low salinity. However, under high salinity, AKT1 and NHX2 were strongly induced, which indicated the transport of K+ and Na+ compartmentalization to maintain ion homeostasis. In addition, A. marina tolerates low salinity by up-regulating ABA signaling pathway and accumulating more mannitol, unsaturated fatty acids, amino acids, and L-ascorbic acid in the roots. Under high salinity, A. marina undergoes a more drastic metabolic network rearrangement in the roots, such as more L-ascorbic acid and oxiglutatione were up-regulated, while carbohydrates, lipids and amino acids were down-regulated in the roots, finally glycolysis and TCA cycle were promoted to provide more energy to improve salt tolerance. Our findings suggest that the major salt tolerance traits in A. marina can be attributed to complex regulatory and signaling mechanisms, and show significant differences between low and high salinity.

2.
Radiat Oncol ; 19(1): 88, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978062

ABSTRACT

PURPOSE: This study aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness. MATERIALS AND METHODS: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance. RESULTS: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P+ < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V50Gy, V40Gy and Dmean for the bladder and rectum, as well as Dmean for the bowel bag, femoral heads, and kidneys (all P+ < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min. CONCLUSION: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning.


Subject(s)
Organs at Risk , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/radiotherapy , Female , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Organs at Risk/radiation effects
3.
Food Chem ; 459: 140429, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39024880

ABSTRACT

The ideal physicochemical properties of bigels are important for food applications. Therefore, a new bigel was prepared based on mixed beef tallow and soybean oil oleogel and deacetylated konjac glucomannan (KGM) hydrogel. The effect of the deacetylation degree of KGM on the physicochemical properties and microstructure of bigels was studied. The bigel containing moderate deacetylation degree of KGM had better rheological properties and hardness (319.84 g) than that with low and high deacetylation degrees of KGM. The interactions among the bigel components were analyzed by Fourier transform infrared spectroscopy and molecular dynamics simulation, indicating that the formation of the bigels was dominated by electrostatic interactions. Overall, the bigels containing moderate deacetylation degree of KGM had better physical properties, which may provide a theoretical foundation to develop bigels with low cholesterol, trans and saturated fats levels to replace traditional solid fats in food industry.

4.
Cancer Med ; 13(14): e70001, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031016

ABSTRACT

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.


Subject(s)
Magnetic Resonance Imaging , Neoadjuvant Therapy , Nomograms , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Middle Aged , Aged , Retrospective Studies , Magnetic Resonance Imaging/methods , Treatment Outcome , ROC Curve , Radiomics
5.
Sci Total Environ ; : 174870, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39029755

ABSTRACT

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

6.
Int Immunopharmacol ; 138: 112623, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38991630

ABSTRACT

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

7.
Article in English | MEDLINE | ID: mdl-38982914

ABSTRACT

Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-ß-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

10.
Ann Surg Oncol ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824192

ABSTRACT

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

11.
Anal Methods ; 16(24): 3839-3846, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38829181

ABSTRACT

The level of sulfur dioxide (SO2) and viscosity in mitochondria play vital roles in various physiological and pathological processes. Abnormalities in mitochondrial SO2 and viscosity are closely associated with numerous biological diseases. It is of great significance to develop novel fluorescence probes for simultaneous detection of SO2 and viscosity within mitochondria. Herein, we have developed a water-soluble, mitochondrial-targeted and near-infrared fluorescent probe, CMBT, for the simultaneous detection of SO2 and viscosity. The probe CMBT incorporates benzothiazolium salt as a mitochondrial targeting moiety and 7-diethylaminocoumarin as a rotor for viscosity detection, respectively. Based on the prompt reaction between nucleophilic HSO3-/SO32- and the backbone of the benzothiazolium salt derivative, probe CMBT displayed high sensitivity and selectivity toward SO2 with a limit of detection as low as 0.17 µM. As viscosity increased, the twisted intramolecular charge transfer (TICT) process was restricted, resulting in fluorescence emission enhancement at 690 nm. Moreover, probe CMBT demonstrated exceptional mitochondrial targeting ability and was successfully employed to image variations of SO2 and viscosity in living cells and mice. The work highlights the great potential of the probe as a convenient tool for revealing the relationship between SO2 and viscosity in biological systems.


Subject(s)
Fluorescent Dyes , Mitochondria , Sulfur Dioxide , Sulfur Dioxide/analysis , Sulfur Dioxide/chemistry , Fluorescent Dyes/chemistry , Animals , Mitochondria/chemistry , Mitochondria/metabolism , Viscosity , Mice , Humans , Optical Imaging/methods , HeLa Cells , Limit of Detection
13.
Heliyon ; 10(11): e31757, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845977

ABSTRACT

Background: The prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly different from those of adult patients, but the knowledge of the disease is generally poor. Methods: English databases (PubMed, Web of Science, Embase, BIOSIS) and Chinese databases (CNKI, Wanfan, VIP) were searched on October 15th, 2022. All the articles of cross-sectional and cohort studies reporting the species composition and lesion site of the NTM disease in children using well-recognized NTM species identification methods were taken into account. Using a random effects model, we assessed the disease lesion sites and the prevalence of different NTM species in pediatric NTM disease. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. Results: The prevalence rates of NTM disease in children ranged between 0.6 and 5.36/100,000 in different countries, and Europe reported the highest prevalence rate. The most common clinical lesion site was lymph node, accounting for 71.1 % (55.0 %-83.2 %), followed by lung (19.3 %, 9.8%-34.4 %)and then skin and soft tissue (16.6 %,13.5%-20.3 %). Mycobacterium avium complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%-69.6 %). Inconsistent with adult patients, Mycobacterium avium accounted for a dominant proportion in MAC than Mycobacterium intracellulare. Conclusions: The lymph node was the most affected organ in pediatric NTM disease, while Mycobacterium avium was the most isolated pathogenic species in children.

14.
ACS Appl Mater Interfaces ; 16(22): 28134-28146, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38768602

ABSTRACT

Vessel transplantation is currently considered the "gold standard" treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based ß-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.


Subject(s)
Biocompatible Materials , Chitosan , Hydrogels , Polyvinyl Alcohol , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Humans , Polyvinyl Alcohol/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Blood Vessel Prosthesis , Materials Testing , beta-Cyclodextrins/chemistry , Human Umbilical Vein Endothelial Cells/drug effects , Cell Proliferation/drug effects , Hemolysis/drug effects , Animals , Platelet Adhesiveness/drug effects , Cross-Linking Reagents/chemistry
15.
Int J Immunopathol Pharmacol ; 38: 3946320241240706, 2024.
Article in English | MEDLINE | ID: mdl-38712735

ABSTRACT

Introduction: Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. Methods: Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. Results: We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. Conclusion: Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.


Subject(s)
Copper Transporter 1 , Urinary Bladder Neoplasms , Aged , Female , Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Copper Transporter 1/genetics , Copper Transporter 1/metabolism , Disease Progression , DNA Methylation , Gene Expression Regulation, Neoplastic , Mutation , Prognosis , Promoter Regions, Genetic , Up-Regulation , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
16.
Nat Commun ; 15(1): 3901, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724505

ABSTRACT

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Subject(s)
Cytoplasm , NF-KappaB Inhibitor alpha , NF-kappa B , Protein-Tyrosine Kinases , Transcription Factor RelA , Animals , Phosphorylation , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/genetics , Mice , Transcription Factor RelA/metabolism , Humans , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , NF-kappa B/metabolism , Cytoplasm/metabolism , Proteolysis , Cell Nucleus/metabolism , Virus Replication , HEK293 Cells , Signal Transduction , Mice, Inbred C57BL , Cytokines/metabolism , Active Transport, Cell Nucleus , Protein Serine-Threonine Kinases
17.
Medicine (Baltimore) ; 103(21): e38254, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788021

ABSTRACT

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.


Subject(s)
Collateral Circulation , Ischemic Stroke , Propensity Score , Serum Albumin , Humans , Male , Collateral Circulation/physiology , Female , Ischemic Stroke/blood , Ischemic Stroke/physiopathology , Ischemic Stroke/etiology , Middle Aged , Aged , Serum Albumin/analysis , Cerebrovascular Circulation/physiology , Intracranial Arteriosclerosis/blood , Intracranial Arteriosclerosis/physiopathology , Intracranial Arteriosclerosis/complications , Retrospective Studies , Logistic Models
18.
Brain ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701344

ABSTRACT

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

20.
Foods ; 13(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38790808

ABSTRACT

α-Dicarbonyl compounds (α-DCs) are commonly present in various foods. We conducted the investigation into concentration changes of α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in fresh fruits and decapped commercial juices during storage at room temperature and 4 °C, as well as in homemade juices during storage at 4 °C. The studies indicate the presence of α-DCs in all samples. The initial contents of 3-DG in the commercial juices (6.74 to 65.61 µg/mL) are higher than those in the homemade ones (1.97 to 4.65 µg/mL) as well as fruits (1.58 to 3.33 µg/g). The initial concentrations of GO and MGO are normally less than 1 µg/mL in all samples. During storage, the α-DC levels in the fruits exhibit an initial increase followed by a subsequent decrease, whereas, in all juices, they tend to accumulate continuously over time. As expected, 4 °C storage reduces the increase rates of the α-DC concentrations in most samples. From the viewpoint of the α-DC contents, fruits and homemade juices should always be the first choice for daily intake of nutrients and commercial juices ought to be mostly avoided.

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