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1.
J Environ Sci (China) ; 147: 370-381, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003055

RESUMEN

Two strains of Fe/Mn oxidizing bacteria tolerant to high concentrations of multiple heavy metal(loid)s and efficient decontamination for them were screened. The surface of the bio-Fe/Mn oxides produced by the oxidation of Fe(II) and Mn(II) by Pseudomonas taiwanensis (marked as P4) and Pseudomonas plecoglossicida (marked as G1) contains rich reactive oxygen functional groups, which play critical roles in the removal efficiency and immobilization of heavy metal(loid)s in co-contamination system. The isolated strains P4 and G1 can grow well in the following environments: pH 5-9, NaCl 0-4%, and temperature 20-30°C. The removal efficiencies of Fe, Pb, As, Zn, Cd, Cu, and Mn are effective after inoculation of the strains P4 and G1 in the simulated water system (the initial concentrations of heavy metal(loid) were 1 mg/L), approximately reaching 96%, 92%, 85%, 67%, 70%, 54% and 15%, respectively. The exchangeable and carbonate bound As, Cd, Pb and Cu are more inclined to convert to the Fe-Mn oxide bound fractions in P4 and G1 treated soil, thereby reducing the phytoavailability and bioaccessible of heavy metal(loid)s. This research provides alternatives method to treat water and soil containing high concentrations of multi-heavy metal(loid)s.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes del Suelo/metabolismo , Oxidación-Reducción , Pseudomonas/metabolismo , Manganeso , Hierro/química , Hierro/metabolismo , Suelo/química , Biodegradación Ambiental , Microbiología del Suelo
2.
Int J Ophthalmol ; 17(9): 1665-1674, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296557

RESUMEN

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

3.
J Am Chem Soc ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298290

RESUMEN

The inevitable dealumination process of zeolite Y is closely related to ultrastabilization, enhanced BroÌ·nsted acidity, and deactivation throughout its life cycle, producing complex aluminum and acidic hydroxyl species. Most investigations on dehydrated zeolites have focused on the BroÌ·nsted acidity of tetra-coordinated Al (Al(IV)) and Lewis acidity associated with tricoordinated Al (Al(III)) sites, which has left the penta-coordinated Al (Al(V)) in dealuminated zeolites scarcely discussed. This is largely due to the oversimplified view of detectable Al(V) as an exclusively extra-framework species with Lewis acidity. Here we report the formation of BroÌ·nsted acidic penta-coordinated Al species (Al(V)-BAS) in the dealumination process. Two-dimensional (2D) through-bond and multiquantum 1H-{27Al} correlation solid-state NMR experiments demonstrate the presence of a bridging Si-OH-Al(V) structure in dealuminated Y zeolites. Different from the conventional belief that water attack leads to the breaking of zeolite framework Al-O bonds in the initial stage of zeolite dealumination, the observed Al(V) as a dealumination intermediate is directly correlated with a BAS pair because of the direct dissociation of water on the framework tetrahedral aluminum (Al(IV)), thus bypassing the cleavage of Al-O bonds. 1H double-quantum solid-state NMR experiments and theoretical calculations provide further evidence for this mechanism, whereas pyridine adsorption experiments confirm stronger acidity of Al(V)-BASs than the traditional bridging hydroxyl groups associated with Al(IV). We were also able to detect the Al(V)-BAS site from dealuminated SSZ-13 zeolite with CHA topology, suggesting that its creation is not specific to the framework structure of zeolites.

4.
J Org Chem ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298672

RESUMEN

In continuation of our research interest in the green oxidation of indoles, we further explore the direct oxidation of 2-methylindoles to 2-formyl indoles promoted by NCS and associated with H2O as the oxygen source. This methodology was demonstrated to be a robust protocol consisting of chlorination, SN2', and oxidation processes, and presents a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the preparation of high added-value versatile building blocks susceptible to further functionalization.

5.
Chem Biol Drug Des ; 104(3): e14635, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300672

RESUMEN

The natural lignan diphyllin has shown promising antitumor activity, although its clinical advancement has been impeded by challenges such as low solubility, poor metabolic stability, and limited potency. In response, we developed and synthesized two sets of diphyllin 4-C derivatives, comprising six ester derivatives and eight 1, 2, 3-triazole derivatives. Notably, among these derivatives, 1, 2, 3-triazole derivatives 7c and 7e demonstrated the most potent cytotoxic effects, with IC50 values ranging from 0.003 to 0.01 µM. Treatment with 0.2 µM of 7c and 7e resulted in a reduction of V-ATPase activity in HGC-27 cells to 23% and 29%, respectively.


Asunto(s)
Antineoplásicos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , ATPasas de Translocación de Protón Vacuolares/antagonistas & inhibidores , ATPasas de Translocación de Protón Vacuolares/metabolismo , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Lignanos/farmacología , Lignanos/química , Lignanos/síntesis química
6.
Mater Today Bio ; 28: 101232, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39315396

RESUMEN

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

7.
Eur J Neurol ; : e16473, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315749

RESUMEN

BACKGROUND AND PURPOSE: The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150-1/300. However, the factors affecting its penetrance remain unclear. Therefore, our study aims to identify modifier genes associated with the incomplete penetrance of this founder mutation. METHODS: Whole-exome sequencing (WES) was performed on 36 participants, including 22 MMD patients and 14 non-MMD controls with RNF213 p.R4810K mutation. Fisher's exact test was used to assess the presence of genetic variants that differed significantly between MMD patients and non-MMD controls. In order to exclude false-positive results, another 55 carriers were included to perform Fisher's exact test for the selected sites in the WES discovery stage. Subsequently, human brain microvascular endothelial cells were transfected with wild-type and mutant HAPLN3 for tube formation assays and western blotting to explore the impact of candidate genes on angiogenesis. RESULTS: Analysis of variants from WES data revealed a total of 12 non-synonymous variants. Through bioinformatics analysis, the focus was on the HAPLN3 p.T34A variant with a significant p value of 0.00731 in Fisher's exact test. Validation through Sanger sequencing confirmed the presence of this variant in the WES data. In vitro experiments revealed that silencing HAPLN3 and transfecting HAPLN3 p.T34A significantly enhanced tube formation and increased the relative protein expression of vascular endothelial growth factor in endothelial cells. CONCLUSIONS: These results suggest that HAPLN3 may function as a modifier gene of RNF213 p.R4810K, promoting the development of MMD and contributing to the incomplete penetrance of MMD founder mutations.

8.
Neuroimage ; : 120858, 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39317273

RESUMEN

Diffusion magnetic resonance imaging (dMRI) allows non-invasive assessment of brain tissue microstructure. Current model-based tissue microstructure reconstruction techniques require a large number of diffusion gradients, which is not clinically feasible due to imaging time constraints, and this has limited the use of tissue microstructure information in clinical settings. Recently, approaches based on deep learning (DL) have achieved promising tissue microstructure reconstruction results using clinically feasible dMRI. However, it remains unclear whether the subtle tissue changes associated with disease or age are properly preserved with DL approaches and whether DL reconstruction results can benefit clinical applications. Here, we provide the first evidence that DL approaches to tissue microstructure reconstruction yield reliable brain tissue microstructure analysis based on clinically feasible dMRI scans. Specifically, we reconstructed tissue microstructure from four different brain dMRI datasets with only 12 diffusion gradients, a clinically feasible protocol, and the neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT) models were considered. With these results we show that disease-related and age-dependent alterations of brain tissue were accurately identified. These findings demonstrate that DL tissue microstructure reconstruction can accurately quantify microstructural alterations in the brain based on clinically feasible dMRI.

9.
Water Res ; 267: 122448, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39305531

RESUMEN

Environmental warming and eutrophication pose significant challenges to shallow lake systems, where dissolved organic matter (DOM) serves as a diverse and intricate mixture of organic macromolecules, playing a pivotal role in aquatic ecosystems. Despite its complexity, comprehending the interplay between environmental changes and DOM composition alterations and their subsequent impacts on aqueous CO2 partial pressure (pCO2) is essential for a better understanding of carbon cycling. Yet, our current understanding in this realm remains limited. To address this gap, mesocosm systems were established to investigate how elevated water temperature and eutrophication, alongside changes in DOM composition, influence pCO2 dynamics. Results indicate that while temperature and nutrient levels do not directly influence pCO2 fluctuations, they indirectly affect aqueous pCO2 through their modulation of DOM composition. Elevated temperature and nutrient concentrations notably enhance both the production and degradation of indigenous protein-like organic matter and increase the accumulation of humic-like organic compounds, with phosphorus released from sediment playing a particularly significant role. Furthermore, the degradation rate of protein-like organic matter significantly exceeds its accumulation rate. On the other hand, the impact of water eutrophication on DOM composition surpasses that of temporal temperature variations, with a 2∼4 °C temperature rise showing minimal effects on DOM composition. Notably, the degradation of protein-like organic matter markedly increases aqueous pCO2, while the rise in humic-like organic matter in water exerts minimal influence on pCO2 concentrations. A comprehensive understanding of carbon cycling processes under environmental changes will facilitate effective management of lake ecosystems and the advancement of carbon mitigation technologies.

10.
Sci Total Environ ; : 176408, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306131

RESUMEN

Guvermectin is a new chemical isolated from the microbial metabolites and is registered as a novel plant growth regulator. However, the biotransformation behavior and toxicity of guvermectin to mammals remain unclear and have unknown implications for consumers or occupationally exposed persons. Therefore, we investigated the biotransformation of guvermectin in vivo and in vitro, its effects on CYP450s activities, and its oral toxicity in rats. The results showed that guvermectin could be rapidly absorbed when administered orally and eliminated rapidly in the serum, with a half-life of 6.3 h. Four phase І metabolism products of guvermectin in the serum were screened and identified using UPLC-QTOF/MS. Two products, adenine and psicofuramine, were confirmed using reference standards. Hydrolysis and oxidation reactions were the main transformation pathways. Oral toxicity tests in rats showed that guvermectin exhibited light toxicity to rats (LC50 > 5000 mg/kg b.w.). However, an in vitro probe drug experiment revealed that guvermectin could induce CYP2D6 activity, and a lower concentration of guvermectin exhibited a stronger effect on CYP2D6 than higher concentration (1.38-fold). Molecular docking studies implied that guvermectin was an antagonist of CYP1A2, CYP2C9, and CYP3A4. These findings provided a better understanding of the environmental and human health risks associated with guvermectin and promote its rational use. However, the potential risk of endocrine disruption cab not be ignored due to the presence of nucleoside-like metabolites.

11.
Sci Total Environ ; 953: 175958, 2024 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-39233077

RESUMEN

A burgeoning body of epidemiological and toxicological evidence suggests that thyroid health may be significantly impacted by exposure to both long- and short-chain perfluoroalkyl substances (PFAS) compounds. We conducted a meta-analysis to examine the association between 16 PFAS compounds and five thyroid hormones (TSH, TT3, TT4, FT3, and FT4) in the serum of a pregnant women, adolescents, and adults. The dose-response relationship between some PFAS and thyroid hormones in different population subpopulation was found and the model was fitted. We also amalgamated data from 18 animal experiments with previously published in vitro studies to elucidate the toxicological mechanisms underlying the impact of PFAS on the thyroid gland. The results of the study showed that (a) both conventional and emerging PFAS compounds were identified in human samples and exhibited associations with thyroid health outcomes; (b) in animal studies, PFAS have been found to impact thyroid gland health through two primary mechanisms: by influencing the hypothalamic-pituitary-thyroid axis and by binding to thyroid receptors. This study provides a systematic description of the health effects and risk assessment associated with PFAS exposure on the thyroid gland. Furthermore, dose-response relationships were established through the Hill model in python.


Asunto(s)
Exposición a Riesgos Ambientales , Contaminantes Ambientales , Fluorocarburos , Glándula Tiroides , Hormonas Tiroideas , Humanos , Femenino , Fluorocarburos/toxicidad , Glándula Tiroides/efectos de los fármacos , Embarazo , Adolescente , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/toxicidad , Hormonas Tiroideas/sangre , Adulto , Animales
12.
Front Physiol ; 15: 1460414, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39308975

RESUMEN

Background: Long-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle. Methods: The cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8 g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis. Results: Hepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle. Conclusion: These findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

13.
Environ Pollut ; 362: 124971, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293654

RESUMEN

Plastic pollution, driven by micro- and nanoplastics (MNPs), poses a major environmental threat, exposing humans through various routes. Despite human colorectal adenocarcinoma Caco-2 cells being used as an in vitro model for studying the intestinal epithelium, uncertainties linger about MNPs harming these cells and the factors influencing adverse effects. Addressing this lacuna, our study aimed to elucidate the pivotal MNP parameters influencing cytotoxicity in Caco-2 cells, employing meta-analysis and machine learning techniques for quantitative assessment. Initial scrutiny of 95 publications yielded 17 that met the inclusion criteria, generating a dataset of 320 data points. This dataset underwent meticulous stratification based on polymer type, exposure time, polymer size, MNP concentration, and biological assays utilised. Subsequent dose-response curve analysis revealed moderate correlations for selected subgroups, such as the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) MTT biological assay and exposure time exceeding 24 h, with coefficient of determination (R2) values of 0.50 (p-value: 0.0065) and 0.60 (p-value: 0.0018) respectively. For the aforementioned two subgroups, the MNP concentrations surpassing 10 µg/mL led to diminished viability of Caco-2 cells. Notably, we observed challenges in employing meta-analysis to navigate this multidimensional MNP dataset. Leveraging a random forest model, we achieved improved predictive performance, with R2 values of 0.79 and a root mean square error (RMSE) of 0.14 for the prediction of the Log Response Ratio on the test set. Model interpretation indicated that size and concentration are the principal drivers influencing Caco-2 cell cytotoxicity. Additionally, the partial dependence plot illustrating the relationship between the size of MNPs and predicted cytotoxicity reveals a complex pattern. Our study provides crucial insights into the health impacts of plastic pollution, informing policymakers for targeted interventions, thus contributing to a comprehensive understanding of its human health consequences.

14.
Pharmacol Res ; 208: 107379, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39218421

RESUMEN

Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB.


Asunto(s)
Antituberculosos , Grafito , Macrófagos , Mycobacterium tuberculosis , Rifampin , Tuberculosis , Grafito/química , Animales , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , Tuberculosis/microbiología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Rifampin/farmacología , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Ratones , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Antituberculosos/administración & dosificación , Autofagia/efectos de los fármacos , Macaca , Nanopartículas , Células RAW 264.7
15.
J Org Chem ; 89(18): 13518-13529, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39253778

RESUMEN

A three-component defluorinative haloalkylation of alkenes with trifluoromethyl compounds and TBAX (X = Cl, Br) via dual photoredox/copper catalysis is reported. The mild conditions are compatible with a wide array of activated trifluoromethyl aromatics bearing diverse substituents, and various nonactivated terminal and internal alkenes, enabling straightforward access to synthetically valuable γ-gem-difluoroalkyl halides with high efficiency. Mechanistic studies indicate that the [Cu] complexes not only serve as XAT catalysts but also facilitate the SET reduction of trifluoromethyl groups by photocatalysts. Additionally, the resulting alkyl halide products can serve as versatile conversion intermediates for the synthesis of a diverse range of γ-gem-difluoroalkyl compounds.

16.
JCI Insight ; 9(17)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39253977

RESUMEN

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further demonstrate that knockdown of NDUFB8, one of the components of complex I in AA BLCA cells, resulted in reduced basal respiration, ATP production, GLS1 expression, and proliferation. Moreover, preclinical studies demonstrate the therapeutic potential of targeting complex I, as evidenced by decreased tumor growth in NDUFB8-depleted AA BLCA tumors. Additionally, genetic and pharmacological inhibition of GLS1 attenuated mitochondrial respiration rates and tumor growth potential in AA BLCA. Taken together, these findings provide insight into BLCA disparity for targeting GLS1-Complex I for future therapy.


Asunto(s)
Negro o Afroamericano , Glutaminasa , Glutamina , Mitocondrias , Fosforilación Oxidativa , Neoplasias de la Vejiga Urinaria , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Negro o Afroamericano/genética , Línea Celular Tumoral , Proliferación Celular , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , Glutaminasa/metabolismo , Glutaminasa/genética , Glutamina/metabolismo , Metabolómica/métodos , Mitocondrias/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética
17.
Sci Total Environ ; 954: 176194, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270874

RESUMEN

Since microplastics (MPs) were first detected in groundwater, an increasing number of studies have focused on groundwater pollution by MPs. However, knowledge of the global properties of groundwater MPs: distribution, concentration, composition, and morphology remains limited, while potential factors regulating their transport and distribution in groundwater, especially the hydrogeological background and climate warming conditions, have been omitted from most analyses. Furthermore, previous field investigations did not assess the risks posed by groundwater MPs to the environment and to human health, a necessary preliminary to remediation. In this work, to promote future MP pollution studies and remediation policies, we assimilated and synthesized the current knowledge on this topic. We reviewed current data on global groundwater pollution by MPs, analyzed the driving factors of their transport and distribution, and summarized the ecological and health hazards posed by MPs, before discussing current knowledge limits and suggesting perspectives for future work.

18.
CNS Neurosci Ther ; 30(9): e70014, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39258805

RESUMEN

AIMS: Extended fasting-postprandial switch intermitting time has been shown to affect Alzheimer's disease (AD). Few studies have investigated the cerebral perfusion response to fasting-postprandial metabolic switching (FMS) in AD patients. We aimed to evaluate the cerebral perfusion response to FMS in AD patients. METHODS: In total, 30 AD patients, 32 mild cognitive impairment (MCI) patients, and 30 healthy control individuals (HCs) were included in the quantification of cerebral perfusion via cerebral blood flow (CBF). The cerebral perfusion response to FMS was defined as the difference (ΔCBF) between fasting and postprandial CBF. RESULTS: Patients with AD had a regional negative ΔCBF in the anterior temporal lobe, part of the occipital lobe and the parietal lobe under FMS stimulation, whereas HCs had no significant ΔCBF. The AD patients had lower ΔCBF values in the right anterior temporal lobe than the MCI patients and HCs. ΔCBF in the anterior temporal lobe was negatively correlated with cognitive severity and cognitive reserve factors in AD patients. CONCLUSIONS: AD patients exhibited a poor ability to maintain cerebral perfusion homeostasis under FMS stimulation. The anterior temporal lobe is a distinct area that responds to FMS in AD patients and negatively correlates with cognitive function.


Asunto(s)
Enfermedad de Alzheimer , Circulación Cerebrovascular , Disfunción Cognitiva , Ayuno , Periodo Posprandial , Humanos , Masculino , Femenino , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Anciano , Circulación Cerebrovascular/fisiología , Periodo Posprandial/fisiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Persona de Mediana Edad , Anciano de 80 o más Años , Neuroimagen/métodos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/irrigación sanguínea , Imagen por Resonancia Magnética
19.
Regen Ther ; 26: 590-598, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39246700

RESUMEN

Ovarian aging leads to endocrine disorders and systemic degeneration of tissue and organ structure and function, seriously affecting women's physical and mental health. Safe and effective treatments for this condition are lacking. Umbilical cord mesenchymal stem cells (UCMSCs), which have multidirectional differentiation potential, show strong self-renewal, secrete bioactive factors and release exosomes, can undergo homing, colonization, integration and differentiation into supporting and functional cells in tissues and organs through direct manipulation and can also improve the tissue microenvironment through paracrine action, promoting cell division, proliferation and microangiogenesis, inhibiting inflammation and apoptosis, reducing oxidative stress, and mediating two-way immune regulation. These processes activate dormant cells, repaired damaged cells, replace necrotic cells, and regenerate fresh cells, restoring the structure and function of the ageing ovary. Furthermore, with the increasing development of UCMSC research and technology, the therapeutic use of UCMSCs is expected to become an effective means for the treatment of ovarian ageing caused by tissue cell ageing, degeneration, and necrosis.

20.
World J Clin Cases ; 12(25): 5697-5705, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39247739

RESUMEN

BACKGROUND: Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide. Of all evolving procedures, Roux-en-Y gastric bypass (RYGB) is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus (T2DM) and obesity. RYGB was introduced in China nearly 20 years ago, but the number of RYGB surgeries only accounts for 3.1% of the total number of weight loss and metabolic surgeries in China, it's effect on Chinese people still needs further study. AIM: To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM. METHODS: Patients with obesity and T2DM who underwent modified gastric bypass, with > 5-year follow-up data, were analyzed. RESULTS: All 37 patients underwent uneventful laparoscopic surgery, no patient was switched to laparotomy during the surgery, and no severe complications were reported. Average weight and body mass index of the patients reduced from 84.6 ± 17.3 (60.0-140.0) kg and 30.9 ± 5.0 (24.7-46.2) kg/m2 to 67.1 ± 12.2 (24.7-46.2) kg and 24.6 ± 3.9 (17.7-36.5) kg/m2, respectively, and fasting plasma glucose and glycated hemoglobin decreased from 7.4 ± 3.4 mmol/L and 8.2% ± 1.7% preoperatively to 6.5 ± 1.3 mmol/L and 6.5% ± 0.9% 5-years postoperatively, respectively. Only 29.7% (11/37) of the patients used hypoglycemic drugs 5-years postoperatively, and the complete remission rate of T2DM was 29.7% (11/37). Triglyceride level reduced significantly but high-density lipoprotein increased significantly (both P < 0.05) compared with those during the preoperative period. Liver and renal function improved significantly postoperatively, and binary logistic regression analysis revealed that the patients' preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB (P = 0.006 and 0.012, respectively). CONCLUSION: The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM, exhibiting satisfactory amelioration of weight problems, hyperglycemia, and combination disease.

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