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1.
Chemosphere ; 362: 142776, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969225

ABSTRACT

Metallic chromium pollution in soil is widespread, which aroused intensive research in recent decades. In mainstream research, most studies use materials with a reducing ability to adsorb and reduce hexavalent chromium. However, comprehensive analyses and systematic verifications of these different materials are scarce. Therefore, this study conducted a meta-analysis of relevant papers published from 2013 to October 2024 to compare and analyze the performance and usage conditions of some common materials, such as iron-based materials, mineral inorganic materials, organic materials, and layered double hydroxide materials. We synthesized 31 papers for 186 pairwise comparisons and selected the Standardized Mean Difference (SMD) as the appropriate effect size for mean-to-mean comparisons. Fe-based materials had the most stable performance based on its numerous data support, while organic materials had the worst performance. The difference in performance between inorganic mineral materials was the greatest, which was closely related to the selection of components. The difference in the effectiveness of inorganic materials was the greatest, which was closely related to the selection of components and there was room for further improvement. Through further analysis of the impact of environmental factors on material performance, it can be concluded that the effect of the material was better under alkaline, non-sandy, low organic matter, and high CEC soil conditions.

2.
Thromb J ; 22(1): 57, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951855

ABSTRACT

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

4.
Biomed Environ Sci ; 37(6): 607-616, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38988111

ABSTRACT

Objective: Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios ( RR) using a fixed-effects model. Results: Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval ( CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users ( RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. Conclusion: Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.


Subject(s)
Asthma , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Obesity , Humans , Asthma/epidemiology , Asthma/prevention & control , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Incidence , Obesity/complications
5.
BMC Psychol ; 12(1): 379, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38978110

ABSTRACT

This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280-0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P < 0.01). Thirdly, stress perception functioned as a mediator in the relationship between childhood trauma and NSSI among high school students (t = 4.65, P < 0.01). The mediation effect occupies 26.56% of the total effect. Furthermore, the teacher-student relationship moderated the mediating effect of stress perception on the link between childhood trauma and NSSI (ß = 0.0736, P < 0.01). Notably, individuals with strong teacher-student relationships exhibited a significant elevation in stress perception upon exposure to childhood trauma. The findings of this study support a moderated mediation model in the association between childhood trauma and NSSI, suggesting profound implications for the development of targeted interventions and prevention strategies among high school students.


Subject(s)
Interpersonal Relations , School Teachers , Self-Injurious Behavior , Stress, Psychological , Students , Humans , Male , Female , Self-Injurious Behavior/psychology , Self-Injurious Behavior/epidemiology , Adolescent , Students/psychology , Students/statistics & numerical data , Stress, Psychological/psychology , China/epidemiology , School Teachers/psychology , School Teachers/statistics & numerical data , Adverse Childhood Experiences/statistics & numerical data , Adverse Childhood Experiences/psychology , Surveys and Questionnaires , Schools/statistics & numerical data , Child , Prevalence
6.
Adv Mater ; : e2403228, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39022846

ABSTRACT

This study investigates the impact of In- and S-vacancy concentrations on the photocatalytic activity of non-centrosymmetric zinc indium sulfide (ZIS) nanosheets for the hydrogen evolution reaction (HER). A positive correlation between the concentrations of dual In and S vacancies and the photocatalytic HER rate over ZIS nanosheets is observed. The piezoelectric polarization, stimulated by low-frequency vortex vibration to ensure the well-dispersion of ZIS nanosheets in solution, plays a crucial role in enhancing photocatalytic HER over the dual-vacancy engineered ZIS nanosheets. The piezoelectric characteristic of the defective ZIS nanosheets is confirmed through the piezopotential response measured using piezoelectric force microscopy. Piezophotocatalytic H2 evolution over the ZIS nanosheets is boosted under accelerated vortex vibrations. The research explores how vacancies alter ZIS's dipole moment and piezoelectric properties, thereby increasing electric potential gradient and improving charge-separation efficiency, through multi-scale simulations, including Density Functional Theory and Finite Element Analysis, and a machine-learning interatomic potential for defect identification. Increased In and S vacancies lead to higher electric potential gradients in ZIS along [100] and [010] directions, attributing to dipole moment and the piezoelectric effect. This research provides a comprehensive exploration of vacancy engineering in ZIS nanosheets, leveraging the piezopotential and dipole field to enhance photocatalytic performances.

8.
Foods ; 13(13)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38998663

ABSTRACT

In the present study, a new degraded konjac glucomannan (DKGM) was prepared using a crude enzyme from abalone (Haliotis discus hannai) viscera, and its physicochemical properties were investigated. After enzymatic hydrolysis, the viscosity of KGM obviously decreased from 15,500 mPa·s to 398 mPa·s. The rheological properties analysis of KGM and DKGMs revealed that they were pseudoplastic fluids, and pseudoplasticity, viscoelasticity, melting temperature, and gelling temperature significantly decreased after enzymatic hydrolysis, especially for KGM-180 and KGM-240. In addition, the molecular weight of KGM decreased from 1.80 × 106 Da, to 0.45 × 106 Da and the polydispersity index increased from 1.17 to 1.83 after 240 min of degradation time. Compared with natural KGM, the smaller particle size distribution of DKGM further suggests enzyme hydrolysis reduces the aggregation of molecular chains with low molecular weight. FT-IR and FESEM analyses showed that the fragmented KMG chain did not affect the structural characteristics of molecular monomers; however, the dense three-dimensional network microstructure formed by intermolecular interaction changed to fragment microstructure after enzyme hydrolysis. These results revealed that the viscosity and rheological properties of KGM could be controlled and effectively changed using crude enzymes from abalone viscera. This work provides theoretical guidance for the promising application of DKGM in the food industry.

9.
Phys Chem Chem Phys ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39036946

ABSTRACT

In this research, a series of K+-intercalated quasi-1D vanadium-based nano-ribbons (KxV2O5 NRs) were synthesized via a facile solvothermal method. The solvation and reductive effects of vanadium oxide precursors (V2O5 powder) on the crystallization and growth of KxV2O5 NRs were studied. Besides, post-heat treatment was performed to improve the crystallinity of KxV2O5 NRs. These KxV2O5 NRs were adopted as active cathodes for potassium-ion batteries (PIBs), whose K+ storage properties were systematically evaluated using various electrochemical methods. The relationship among the morphology, crystallinity, working voltage window and electrochemical reversible K+ storage performance of KxV2O5 NRs was studied and established. Results reveal that KxV2O5-HG, which was prepared via a solvothermal reaction involving a solvation process (using H2O2) and a proper reducing condition (proper dose of glucose) with V2O5 powder as the raw material, would be more beneficial for the reversible storage of K+ when used as the cathode for PIBs compared to other contrast samples. In addition, the enhanced crystallinity and slightly broadened working voltage window of KxV2O5-HG could hinder its long-term cycling stability upon repeated K+ insertions/extractions.

10.
J Med Case Rep ; 18(1): 295, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38890660

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 have a high incidence of thrombosis that decreases after recovery. When coronavirus disease 2019 is accompanied by diseases prone to thrombosis, risk of post-infection thrombotic events may increase. CASE PRESENTATION: We report a case of digital ischemic gangrene in a 24-year-old Chinese female with systemic lupus erythematosus after recovery from coronavirus disease 2019. The pathogenesis was related to clinical characteristics of systemic lupus erythematosus, hypercoagulability caused by coronavirus disease 2019, and second-hit due to viral infection. CONCLUSION: Patients with autoimmune diseases should remain alert to autoimmune system disorders induced by severe acute respiratory syndrome coronavirus 2 and other viruses. Treatment for these patients should be strictly standardized, and appropriate anticoagulation methods should be selected to prevent thrombosis.


Subject(s)
COVID-19 , Gangrene , Ischemia , Lupus Erythematosus, Systemic , Humans , Female , COVID-19/complications , Lupus Erythematosus, Systemic/complications , Young Adult , Ischemia/etiology , Gangrene/etiology , Fingers/pathology , Fingers/blood supply , SARS-CoV-2 , Necrosis , Anticoagulants/therapeutic use
12.
Thromb J ; 22(1): 47, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840142

ABSTRACT

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

13.
Clin Immunol ; 265: 110293, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38936523

ABSTRACT

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.


Subject(s)
CARD Signaling Adaptor Proteins , Humans , CARD Signaling Adaptor Proteins/genetics , CARD Signaling Adaptor Proteins/deficiency , Female , Young Adult , Mutation , Neutrophils/immunology , Th17 Cells/immunology , Candidiasis, Chronic Mucocutaneous/genetics , Candidiasis, Chronic Mucocutaneous/immunology , Monocytes/immunology , Cytokines
14.
Zool Res ; 45(4): 781-790, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38894521

ABSTRACT

Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. We then inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice, with AAV13-587-7m8 infection retaining a limited spread range. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.


Subject(s)
Dependovirus , Mice, Inbred C57BL , Dependovirus/genetics , Animals , Humans , Mice , HEK293 Cells , Transduction, Genetic , Capsid Proteins/genetics , Capsid Proteins/metabolism
15.
bioRxiv ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38826297

ABSTRACT

Cell type specific (CTS) analysis is essential to reveal biological insights obscured in bulk tissue data. However, single-cell (sc) or single-nuclei (sn) resolution data are still cost-prohibitive for large-scale samples. Thus, computational methods to perform deconvolution from bulk tissue data are highly valuable. We here present EPIC-unmix, a novel two-step empirical Bayesian method integrating reference sc/sn RNA-seq data and bulk RNA-seq data from target samples to enhance the accuracy of CTS inference. We demonstrate through comprehensive simulations across three tissues that EPIC-unmix achieved 4.6% - 109.8% higher accuracy compared to alternative methods. By applying EPIC-unmix to human bulk brain RNA-seq data from the ROSMAP and MSBB cohorts, we identified multiple genes differentially expressed between Alzheimer's disease (AD) cases versus controls in a CTS manner, including 57.4% novel genes not identified using similar sample size sc/snRNA-seq data, indicating the power of our in-silico approach. Among the 6-69% overlapping, 83%-100% are in consistent direction with those from sc/snRNA-seq data, supporting the reliability of our findings. EPIC-unmix inferred CTS expression profiles similarly empowers CTS eQTL analysis. Among the novel eQTLs, we highlight a microglia eQTL for AD risk gene AP3B2, obscured in bulk and missed by sc/snRNA-seq based eQTL analysis. The variant resides in a microglia-specific cCRE, forming chromatin loop with AP3B2 promoter region in microglia. Taken together, we believe EPIC-unmix will be a valuable tool to enable more powerful CTS analysis.

16.
Int J Biol Macromol ; 275(Pt 1): 133522, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945325

ABSTRACT

A facile biphasic system composed of choline chloride (ChCl)-based deep eutectic solvent (DES) and methyl isobutyl ketone (MIBK) was developed to realize the furfural production, lignin separation and preparation of fermentable glucose from Eucalyptus in one-pot. Results showed that the ChCl/1,2-propanediol/MIBK system owned the best property to convert hemicelluloses into furfural. Under the optimal conditions (MRChCl:1,2-propanediol = 1:2, raw materials:DES:MIBK ratio = 1:4:8 g/g/mL, 0.075 mol/L AlCl3·6H2O, 140 °C, and 90 min), the furfural yield and glucose yield reached 65.0 and 92.2 %, respectively. Meanwhile, the lignin with low molecular weight (1250-1930 g/mol), low polydispersity (DM = 1.25-1.53) and high purity (only 0.08-2.59 % carbohydrate content) was regenerated from the biphasic system. With the increase of pretreatment temperature, the ß-O-4, ß-ß and ß-5 linkages in the regenerated lignin were gradually broken, and the content of phenolic hydroxyl groups increased, but the content of aliphatic hydroxyl groups decreased. This research provides a new strategy for the comprehensive utilization of lignocellulose in biorefinery process.

17.
Burns Trauma ; 12: tkae004, 2024.
Article in English | MEDLINE | ID: mdl-38817684

ABSTRACT

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

18.
J Inorg Biochem ; 257: 112585, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38718498

ABSTRACT

Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 âˆ¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 âˆ¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Ferroptosis , Mitochondria , Ruthenium , Ferroptosis/drug effects , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Ruthenium/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Hep G2 Cells , Reactive Oxygen Species/metabolism , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Mice, Nude , Xenograft Model Antitumor Assays , Oxyquinoline/chemistry , Oxyquinoline/pharmacology , Lipid Peroxidation/drug effects , Mice, Inbred BALB C
19.
J Am Heart Assoc ; 13(11): e033981, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38818928

ABSTRACT

BACKGROUND: Oxidative stress plays a principal role in the pathogenesis of white matter hyperintensities (WMHs). The induction of heme oxygenase-1 (HO-1) gene in the brain represents 1 of the pivotal mechanisms to counteract the noxious effects of reactive oxygen species, and the transcriptional modulation of HO-1 induction depends on the length of a GT-repeat (GT)n in the promoter region. We investigated whether the HO-1 gene (GT)n polymorphism is associated with the risk of WMHs. METHODS AND RESULTS: A total of 849 subjects from the memory clinic were consecutively enrolled, and the HO-1 (GT)n genotype was determined. WMHs were assessed with the Fazekas scale and further divided into periventricular WMHs and deep WMHs (DWMHs). Allelic HO-1 (GT)n polymorphisms were classified as short (≤24 (GT)n), median (25≤[GT]n<31), or long (31≤[GT]n). Multivariate logistic regression analysis was used to evaluate the effect of the HO-1 (GT)n variants on WMHs. The number of repetitions of the HO-1 gene (GT)n ranged from 15 to 39 with a bimodal distribution at lengths 23 and 30. The proportion of S/S genotypes was higher for moderate/severe DWMHs than none/mild DWMHs (22.22% versus 12.44%; P=0.001), but the association for periventricular WMHs was not statistically significant. Logistic regression suggested that the S/S genotype was significantly associated with moderate/severe DWMHs (S/S versus non-S/S: odds ratio, 2.001 [95% CI, 1.323-3.027]; P<0.001). The HO-1 gene (GT)n S/S genotype and aging synergistically contributed to the progression of DWMHs (relative excess risk attributable to interaction, 6.032 [95% CI, 0.149-11.915]). CONCLUSIONS: Short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from DWMHs, but not periventricular WMHs. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100045869.


Subject(s)
Genetic Predisposition to Disease , Heme Oxygenase-1 , Humans , Heme Oxygenase-1/genetics , Male , Female , Aged , Middle Aged , Polymorphism, Genetic , White Matter/diagnostic imaging , White Matter/pathology , Risk Factors , Magnetic Resonance Imaging , Promoter Regions, Genetic , Leukoencephalopathies/genetics , Leukoencephalopathies/diagnostic imaging , Phenotype
20.
Am J Physiol Renal Physiol ; 327(1): F158-F170, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38779755

ABSTRACT

Diabetes is closely associated with K+ disturbances during disease progression and treatment. However, it remains unclear whether K+ imbalance occurs in diabetes with normal kidney function. In this study, we examined the effects of dietary K+ intake on systemic K+ balance and renal K+ handling in streptozotocin (STZ)-induced diabetic mice. The control and STZ mice were fed low or high K+ diet for 7 days to investigate the role of dietary K+ intake in renal K+ excretion and K+ homeostasis and to explore the underlying mechanism by evaluating K+ secretion-related transport proteins in distal nephrons. K+-deficient diet caused excessive urinary K+ loss, decreased daily K+ balance, and led to severe hypokalemia in STZ mice compared with control mice. In contrast, STZ mice showed an increased daily K+ balance and elevated plasma K+ level under K+-loading conditions. Dysregulation of the NaCl cotransporter (NCC), epithelial Na+ channel (ENaC), and renal outer medullary K+ channel (ROMK) was observed in diabetic mice fed either low or high K+ diet. Moreover, amiloride treatment reduced urinary K+ excretion and corrected hypokalemia in K+-restricted STZ mice. On the other hand, inhibition of SGLT2 by dapagliflozin promoted urinary K+ excretion and normalized plasma K+ levels in K+-supplemented STZ mice, at least partly by increasing ENaC activity. We conclude that STZ mice exhibited abnormal K+ balance and impaired renal K+ handling under either low or high K+ diet, which could be primarily attributed to the dysfunction of ENaC-dependent renal K+ excretion pathway, despite the possible role of NCC.NEW & NOTEWORTHY Neither low dietary K+ intake nor high dietary K+ intake effectively modulates renal K+ excretion and K+ homeostasis in STZ mice, which is closely related to the abnormality of ENaC expression and activity. SGLT2 inhibitor increases urinary K+ excretion and reduces plasma K+ level in STZ mice under high dietary K+ intake, an effect that may be partly due to the upregulation of ENaC activity.


Subject(s)
Diabetes Mellitus, Experimental , Epithelial Sodium Channels , Potassium, Dietary , Potassium , Animals , Diabetes Mellitus, Experimental/metabolism , Potassium/metabolism , Potassium/urine , Male , Potassium, Dietary/metabolism , Epithelial Sodium Channels/metabolism , Mice, Inbred C57BL , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels, Inwardly Rectifying/genetics , Mice , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/etiology , Diabetic Nephropathies/physiopathology , Kidney/metabolism , Kidney/drug effects , Kidney/physiopathology , Hypokalemia/metabolism , Amiloride/pharmacology , Renal Elimination/drug effects , Homeostasis , Solute Carrier Family 12, Member 3/metabolism , Solute Carrier Family 12, Member 3/genetics , Glucosides/pharmacology , Streptozocin , Benzhydryl Compounds , Sodium-Glucose Transporter 2
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