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2.
Front Mol Neurosci ; 17: 1375925, 2024.
Article in English | MEDLINE | ID: mdl-38807922

ABSTRACT

Zinc transporter 3 (ZnT3) is abundantly expressed in the brain, residing in synaptic vesicles, where it plays important roles in controlling the luminal zinc levels. In this study, we found that ZnT3 knockout in mice decreased zinc levels in the hippocampus and cortex, and was associated with progressive cognitive impairments, assessed at 2, 6, and 9-month of age. The results of Golgi-Cox staining demonstrated that ZnT3 deficiency was associated with an increase in dendritic complexity and a decrease in the density of mature dendritic spines, indicating potential synaptic plasticity deficit. Since ZnT3 deficiency was previously linked to glucose metabolism abnormalities, we tested the expression levels of genes related to insulin signaling pathway in the hippocampus and cortex. We found that the Expression of glucose transporters, GLUT3, GLUT4, and the insulin receptor in the whole tissue and synaptosome fraction of the hippocampus of the ZnT3 knockout mice were significantly reduced, as compared to wild-type controls. Expression of AKT (A serine/threonine protein kinase) and insulin-induced AKT phosphorylation was also reduced in the hippocampus of ZnT3 knockout mice. We hypothesize that the ZnT3 deficiency and reduced brain zinc levels may cause cognitive impairment by negatively affecting glycose metabolism via decreased expression of key components of insulin signaling, as well as via changes in synaptic plasticity. These finding may provide new therapeutic target for treatments of neurodegenerative disorders.

3.
Neural Regen Res ; 19(9): 2075-2080, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38227538

ABSTRACT

JOURNAL/nrgr/04.03/01300535-202409000-00041/figure1/v/2024-01-16T170235Z/r/image-tiff The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor. In 2018, the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital. This prospective, single center, open-label, single-arm study was part of a worldwide prospective multicenter clinical trial (ClinicalTrials.gov Identifier: NCT03253991) conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population. From 2019 to 2020, 10 patients with medication refractory essential tremor were recruited into this open-label, single arm study. The treatment efficacy was determined using the Clinical Rating Scale for Tremor. Safety was evaluated according to the incidence and severity of adverse events. All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus. At the baseline assessment, the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3 ± 3.6, and this improved after treatment to 23.1 ± 6.4 at a 12-month follow-up assessment. A total of 50 adverse events were recorded, and 2 were defined as serious. The most common intraoperative adverse events were nausea and headache. The most frequent postoperative adverse events were paresthesia and equilibrium disorder. Most of the adverse events were mild and usually disappeared within a few days. Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective, with a good safety profile, for patients in Chinese mainland.

4.
J Hazard Mater ; 465: 133183, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38070267

ABSTRACT

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS.


Subject(s)
Adipogenesis , Lipid Metabolism , Polybrominated Biphenyls , Animals , Mice , 3T3-L1 Cells , Cell Differentiation , Glycerophospholipids/pharmacology
5.
J Sci Food Agric ; 104(4): 2449-2457, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37961839

ABSTRACT

BACKGROUND: The shortage of water resources and the increase of greenhouse gas emissions from soil seriously restrict the sustainable development of agriculture. Under the premise of ensuring a stable yield of winter wheat through a reasonable irrigation scenario, identifying a suitable straw returning method will have a positive effect on agricultural carbon sequestration and emission reduction in North China Plain. RESULTS: Straw burying (SR) and straw mulching (SM) were adopted based on traditional tillage under in the winter wheat growing season of 2020-2021 and 2021-2022. Three irrigation scenarios were used for each straw returning method: no irrigation (I0), irrigation 60 mm at jointing stage (I1), and irrigation of 60 mm each at the jointing and heading stages (I2). Soil moisture, soil respiration rate, cumulative soil CO2 emissions, yield, water use efficiency (WUE) and soil CO2 emission efficiency (CEE) were mainly studied. The results showed that, compared to SM, SR improved the utilization of soil water and enhanced soil carbon sequestration. SR reduced soil respiration rate and cumulative soil CO2 emissions in two winter wheat growing seasons, and increased yield by increasing spike numbers. In addition, with an increase in the amount of irrigation, soil CO2 emissions and yield increased. Under SR-I1 treatment, WUE and CEE were the highest. SR-I1 increases crop yields at the same time as reducing soil CO2 emissions. CONCLUSION: The combination of SR and irrigation 60 mm at jointing stage is a suitable straw returning irrigation scenario, which can improve water use and reduce soil CO2 emission in NCP. © 2023 Society of Chemical Industry.


Subject(s)
Soil , Triticum , Seasons , Carbon Dioxide/analysis , Water , Carbon , Agriculture/methods , China
7.
Cell Signal ; 112: 110914, 2023 12.
Article in English | MEDLINE | ID: mdl-37806541

ABSTRACT

Butyrophilin subfamily 3 member A3 (BTN3A3) is a member of the immunoglobulin superfamily and functions as a tumor suppressor in multiple cancer types. Our study has revealed that in clear cell renal cell carcinoma (ccRCC), patients who express high levels of BTN3A3 experience longer survival times than those with lower expression. Further, we have observed that BTN3A3 inhibits the proliferation, migration, and invasion of ccRCC cells. Through the utilization of an immunoprecipitation assay followed by mass spectrometry, we have discovered that BTN3A3 binds directly to RPS3A. Knockdown of BTN3A3 led to increased cell proliferation, migration, and invasion. However, this effect was significantly reduced when RPS3A was simultaneously overexpressed. Previous reports have demonstrated that RPS3A positively regulates mitochondrial function and reactive oxygen species (ROS) levels. Our study has shown that overexpression of both BTN3A3 and RPS3A can increase cellular oxygen consumption rate (OCR) and ROS levels. Furthermore, we have observed that the addition of H2O2 can reverse the effects of BTN3A3 knockdown on cell proliferation and migration by increasing the cellular ROS level. ROS play a crucial role in regulating the MAPK pathway and tumor cell growth. To further explore this relationship, we examined RNA-Seq and immunoblotting data and found that BTN3A3 can negatively regulate the degree of activation of the MAPK signaling pathway. This finding suggests that the BTN3A3/RPS3A complex may regulate ccRCC progression by modulating MAPK pathways. Therefore, BTN3A3 could serve as both a prognostic marker and a potential therapeutic target for ccRCC patients.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Cell Line, Tumor , Neoplasm Invasiveness/genetics , Cell Proliferation , Cell Movement , Gene Expression Regulation, Neoplastic
8.
Pharmaceutics ; 15(10)2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37896250

ABSTRACT

Bacteria and bacterial components possess multifunctional properties, making them attractive natural bio-nanocarriers for cancer diagnosis and targeted treatment. The inherent tropic and motile nature of bacteria allows them to grow and colonize in hypoxic tumor microenvironments more readily than conventional therapeutic agents and other nanomedicines. However, concerns over biosafety, limited antitumor efficiency, and unclear tumor-targeting mechanisms have restricted the clinical translation and application of natural bio-nanocarriers based on bacteria and bacterial components. Fortunately, bacterial therapies combined with engineering strategies and nanotechnology may be able to reverse a number of challenges for bacterial/bacterial component-based cancer biotherapies. Meanwhile, the combined strategies tend to enhance the versatility of bionanoplasmic nanoplatforms to improve biosafety and inhibit tumorigenesis and metastasis. This review summarizes the advantages and challenges of bacteria and bacterial components in cancer therapy, outlines combinatorial strategies for nanocarriers and bacterial/bacterial components, and discusses their clinical applications.

9.
Mil Med Res ; 10(1): 22, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37189155

ABSTRACT

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients' anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.


Subject(s)
Artificial Intelligence , Neoplasms , Humans , Reproducibility of Results , Neoplasms/diagnostic imaging , Prognosis , Machine Learning
10.
Sci Total Environ ; 878: 163247, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37011687

ABSTRACT

Assessing soil quality variation during the prolonged application of mulched drip irrigation (MDI) is critical to comprehend the sustainability of arid agriculture. To investigate the dynamics of crucial soil-quality indicators caused by the long-term application of MDI, the "space instead of time" methodology was adopted, and six fields were selected to represent the primary successional sequence in Northwest China. A total of 21 vital soil attributes from 18 samples were used as soil quality indicators. Based on the soil quality index calculated from the entire datasets, it was observed that long-term MDI practice enhanced soil quality by 28.21 %-74.36 % due to improvements in soil structure (e.g., soil bulk density, three-phase ratio, and aggregates stability) and nutrients (including total carbon, organic carbon, total nitrogen, and available phosphorus). Compared to natural unirrigated soil, soil salinity in 0-200 cm depth significantly decreased by 51.34 %-92.39 % in cotton fields with increasing years of practicing MDI. In addition, long-term MDI practice restructured soil microbial communities and augmented microbial activity by 259.48 %-502.90 % relative to the natural salt-affected soil. However, soil quality stabilized after 12-14 years of MDI application due to accumulated residual plastic fragments, increased bulk density, and reduced microbial diversity. Overall, practicing long-term MDI promotes soil quality and crop yield by promoting soil microbiome structure and function and soil structure. However, long-term mono-cropping with MDI would result in soil compaction and impair microbial activity.

11.
Dis Markers ; 2023: 3560340, 2023.
Article in English | MEDLINE | ID: mdl-36755802

ABSTRACT

Methods: Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results: Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion: This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Transcription Factors/genetics , Gene Regulatory Networks , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Computational Biology , Prognosis , RNA, Messenger/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism
12.
Front Microbiol ; 14: 1064358, 2023.
Article in English | MEDLINE | ID: mdl-36819023

ABSTRACT

Soil salinization and acidification seriously damage soil health and restricts the sustainable development of planting. Excessive application of chemical fertilizer and other reasons will lead to soil acidification and salinization. This study focus on acid and salinized soil, investigated the effect of phosphate-solubilizing bacteria, Aspergillus niger MJ1 combined with nitrogen-fixing bacteria Pseudomonas stutzeri DSM4166 or mutant Pseudomonas fluorescens CHA0-nif on crop quality, soil physicochemical properties, and microbial communities. A total of 5 treatments were set: regular fertilization (T1), regular fertilization with MJ1 and DSM4166 (T2), regular fertilization with MJ1 and CHA0-nif (T3), 30%-reducing fertilization with MJ1 and DSM4166 (T4), and 30%-reducing fertilization with MJ1 and CHA0-nif (T5). It was found that the soil properties (OM, HN, TN, AP, AK, and SS) and crop quality of cucumber (yield production, protein, and vitamin C) and lettuce (yield production, vitamin C, nitrate, soluble protein, and crude fiber) showed a significant response to the inoculated strains. The combination of MJ1 with DSM4166 or CHA0-nif influenced the diversity and richness of bacterial community in the lettuce-grown soil. The organismal system-, cellular process-, and metabolism-correlated bacteria and saprophytic fungi were enriched, which were speculated to mediate the response to inoculated strains. pH, OM, HN, and TN were identified to be the major factors correlated with the soil microbial community. The inoculation of MJ1 with DSM4166 and CHA0-nif could meet the requirement of lettuce and cucumber growth after reducing fertilization in acid and salinized soil, which provides a novel candidate for the eco-friendly technique to meet the carbon-neutral topic.

13.
Org Biomol Chem ; 21(6): 1270-1274, 2023 02 08.
Article in English | MEDLINE | ID: mdl-36637117

ABSTRACT

Based on aggregation-induced emission (AIE) and twisted intramolecular charge transfer (TICT) mechanisms, a fluorescent probe SWJT-12 for the detection of ClO- was designed by using the CN bond as a reactive group. This synthesized probe can react with ClO- in a high aqueous phase, and it shows a large Stokes shift (144 nm) and low biological toxicity. Its limit of detection was calculated to be 0.28 µM. Furthermore, SWJT-12 was successfully used for ratiometric imaging of the exogenous hypochlorite anion in living cells.


Subject(s)
Hypochlorous Acid , Optical Imaging , Humans , HeLa Cells , Microscopy, Fluorescence , Fluorescent Dyes/chemistry
14.
Sci Total Environ ; 863: 161029, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36549533

ABSTRACT

In drylands, soil microorganisms play a vital role in restoring degraded soils, and soil microbiota is significantly affected by human activities and climate events, such as seasonal freezing and thawing. However, the response of soil microbes to freezing and thawing, as well as their properties in drylands agroecosystems, remains unknown. This study investigated the effects of seasonal freezing and thawing on soil fungal and bacterial communities, multifunctionality, and soil microbial quality in a dryland agroecosystem. It has been observed that seasonal freezing and thawing promoted nutrient releases such as total carbon and available phosphorus. After thawing, soil catalase and cellulase activities increased while acid phosphatase and urease activities and total nitrogen content at topsoil decreased. Soil microbial biomass carbon content at 0-40 cm depth was significantly reduced by 94.77 %. Importantly, freezing and thawing considerably shifted the composition of fungal groups, while the soil bacterial community exhibited more stress tolerance to freezing-thawing. Compared to pre-freezing, the relative abundance of dominant fungal phyla such as Basidiomycota and Mortierellomycota decreased. At the same time, Ascomycota increased after thawing, and the relative abundance of pathogenic fungus also increased. For dominant bacteria phylum, freezing and thawing increased the relative abundance of Proteobacteria and Gemmatimonadetes while Micrococcaceae declined. Freezing and thawing significantly increased bacterial diversity and evenness by 4.94 % and 4.19 %, respectively, but decreased fungal richness and diversity by 23.49 % and 14.91 %, respectively. The minimum and total data sets were used to evaluate soil quality and we found that freezing and thawing significantly negatively impacted soil multifunctionality and microbial quality. In summary, this study demonstrates that the seasonal freezing-thawing has a significant negative impact on soil microbial quality and multifunctionality, and accelerates soil degeneration in dryland agroecosystem.


Subject(s)
Soil Microbiology , Soil , Humans , Freezing , Bacteria , China , Carbon
15.
J Biol Chem ; 299(2): 102819, 2023 02.
Article in English | MEDLINE | ID: mdl-36549648

ABSTRACT

Zinc (Zn) is an essential trace element; it serves as a cofactor for a great number of enzymes, transcription factors, receptors, and other proteins. Zinc is also an important signaling molecule, which can be released from intracellular stores into the cytosol or extracellular space, for example, during synaptic transmission. Amongst cellular effects of zinc is activation of Kv7 (KCNQ, M-type) voltage-gated potassium channels. Here, we investigated relationships between Kv7 channel inhibition by Ca2+/calmodulin (CaM) and zinc-mediated potentiation. We show that Zn2+ ionophore, zinc pyrithione (ZnPy), can prevent or reverse Ca2+/CaM-mediated inhibition of Kv7.2. In the presence of both Ca2+ and Zn2+, the Kv7.2 channels lose most of their voltage dependence and lock in an open state. In addition, we demonstrate that mutations that interfere with CaM binding to Kv7.2 and Kv7.3 reduced channel membrane abundance and activity, but these mutants retained zinc sensitivity. Moreover, the relative efficacy of ZnPy to activate these mutants was generally greater, compared with the WT channels. Finally, we show that zinc sensitivity was retained in Kv7.2 channels assembled with mutant CaM with all four EF hands disabled, suggesting that it is unlikely to be mediated by CaM. Taken together, our findings indicate that zinc is a potent Kv7 stabilizer, which may protect these channels from physiological inhibitory effects of neurotransmitters and neuromodulators, protecting neurons from overactivity.


Subject(s)
Calcium , Calmodulin , Intracellular Space , KCNQ Potassium Channels , Zinc , Calcium Signaling , Calmodulin/metabolism , KCNQ Potassium Channels/antagonists & inhibitors , KCNQ Potassium Channels/chemistry , KCNQ Potassium Channels/genetics , KCNQ Potassium Channels/metabolism , Mutation , Protein Binding/genetics , Zinc/pharmacology , Zinc/metabolism , Intracellular Space/metabolism , Calcium/metabolism , KCNQ2 Potassium Channel/antagonists & inhibitors , KCNQ2 Potassium Channel/chemistry , KCNQ2 Potassium Channel/genetics , KCNQ2 Potassium Channel/metabolism , KCNQ3 Potassium Channel/antagonists & inhibitors , KCNQ3 Potassium Channel/chemistry , KCNQ3 Potassium Channel/genetics , KCNQ3 Potassium Channel/metabolism
16.
Bioorg Chem ; 131: 106329, 2023 02.
Article in English | MEDLINE | ID: mdl-36565674

ABSTRACT

A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.


Subject(s)
Antineoplastic Agents , Diterpenes , Euphorbia , Humans , Cell Line, Tumor , Diterpenes/chemical synthesis , Diterpenes/pharmacology , Euphorbia/chemistry , Hep G2 Cells , Molecular Docking Simulation , Molecular Structure , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
17.
Micromachines (Basel) ; 13(12)2022 Dec 17.
Article in English | MEDLINE | ID: mdl-36557544

ABSTRACT

The rapid electrokinetic patterning (REP) technique has been demonstrated to enable dynamic particle manipulation in biomedical applications. Previous studies on REP have generally considered particles with a size less than 5 µm. In this study, a REP platform was used to manipulate polystyrene particles with a size of 3~11 µm in a microfluidic channel sandwiched between two ITO conductive glass plates. The effects of the synergy force produced by the REP electrothermal vortex on the particle motion were investigated numerically for fixed values of the laser power, AC driving voltage, and AC driving frequency, respectively. The simulation results showed that the particles were subject to a competition effect between the drag force produced by the toroidal vortex, which prompted the particles to recirculate in the bulk flow adjacent to the laser illumination spot on the lower electrode, and the trapping force produced by the particle and electrode interactions, which prompted the particles to aggregate in clusters on the surface of the illuminated spot. The experimental results showed that as the laser power increased, the toroidal flow range over which the particles circulated in the bulk flow increased, while the cluster range over which the particles were trapped on the electrode surface reduced. The results additionally showed that the particle velocity increased with an increasing laser power, particularly for particles with a smaller size. The excitation frequency at which the particles were trapped on the illuminated hot-spot reduced as the particle size increased. The force and velocity of polystyrene particles by the REP toroidal vortex has implications for further investigating the motion behavior at the biological cell level.

18.
Front Cardiovasc Med ; 9: 928701, 2022.
Article in English | MEDLINE | ID: mdl-36352848

ABSTRACT

The prevalence and severity of hypertension-induced cognitive impairment increase with the prolonging of hypertension. The mechanisms of cognitive impairment induced by hypertension primarily include cerebral blood flow perfusion imbalance, white and gray matter injury with blood-brain barrier disruption, neuroinflammation and amyloid-beta deposition, genetic polymorphisms and variants, and instability of blood pressure. High homocysteine (HHcy) is an independent risk factor for hypertension that also increases the risk of developing early cognitive impairment. Homocysteine (Hcy) levels increase in patients with cognitive impairment induced by hypertension. This review summarizes a new mechanism whereby HHcy-mediated aberrant DNA methylation and exacerbate hypertension. It involves changes in Hcy-dependent DNA methylation products, such as methionine adenosyltransferase, DNA methyltransferases, S-adenosylmethionine, S-adenosylhomocysteine, and methylenetetrahydrofolate reductase (MTHFR). The mechanism also involves DNA methylation changes in the genes of hypertension patients, such as brain-derived neurotrophic factor, apolipoprotein E4, and estrogen receptor alpha, which contribute to learning, memory, and attention deficits. Studies have shown that methionine (Met) induces hypertension in mice. Moreover, DNA hypermethylation leads to cognitive behavioral changes alongside oligodendroglial and/or myelin deficits in Met-induced mice. Taken together, these studies demonstrate that DNA methylation regulates cognitive dysfunction in patients with hypertension. A better understanding of the function and mechanism underlying the effect of Hcy-dependent DNA methylation on hypertension-induced cognitive impairment will be valuable for early diagnosis, interventions, and prevention of further cognitive defects induced by hypertension.

19.
World Neurosurg ; 168: e562-e569, 2022 12.
Article in English | MEDLINE | ID: mdl-36244665

ABSTRACT

BACKGROUND: The use of Fourier transform infrared spectroscopy to identify the peritumoral tissue of gliomas proves the potential of this technique to distinguish normal brain tissues from glioma tissues. However, due to the heterogeneity of gliomas, it is difficult to characterize the representative spectra of normal brain tissues and glioma tissues. The linear spectra of major cellular components, such as microglia, astrocytes, and glioma cells, were obtained to quantify the biochemical changes between healthy cells and tumor cells, and provide supporting data for the final distinction between tumor and normal brain tissue. METHODS: Fourier transform infrared was used to measure human astrocytes, microglia (HM1900), and glioma cells (U87, BT325), and the cellular components of the 4 types of cells were analyzed by means of average spectra, second-derivative spectra, principal component analysis, hierarchical cluster analysis, and difference spectra. RESULTS: The proteomics, lipidomics, genomics, and metabolic statuses of the cells were different. The amide I, lipid, and nuclear acid regions of the spectra are the most obvious regions to use for distinguishing the 4 types of cells. CONCLUSIONS: We conclude that an improved understanding of both similarities and differences in the cellular components of astrocytes, microglia, and glioma cells can help us better understand the heterogeneity of gliomas. We suggest that targeting cellular metabolism (protein, lipid, and nuclear acids) is helpful to distinguish between normal brain tissue and glioma tissue, which has broad application prospects.


Subject(s)
Brain Neoplasms , Glioma , Humans , Spectroscopy, Fourier Transform Infrared/methods , Brain Neoplasms/pathology , Glioma/pathology , Astrocytes/metabolism , Lipids/analysis
20.
Genet Res (Camb) ; 2022: 7067743, 2022.
Article in English | MEDLINE | ID: mdl-36262249

ABSTRACT

Among primary liver carcinoma cases, the proportion of liver hepatocellular carcinoma (LIHC) cases is 75%-85%. Current treatments for LIHC include chemotherapy, surgical excision, and liver transplantation, which are effective for early LIHC treatment. Nevertheless, the early symptoms of liver carcinoma are atypical, so a large proportion of LIHC patients are diagnosed at an advanced stage. Histocompatibility minor 13 (HM13), located in the endoplasmic reticulum, is responsible for catalysing the hydrolysis of some signal peptides after cleavage from the precursor protein. Here, we studied the role of HM13 in LIHC development through bioinformatics analysis. Database analysis showed that HM13 was of great significance for LIHC tumorigenesis. Compared to normal liver tissues, HM13 expression was increased to a greater extent in LIHC tissues. After analysis of Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, we discovered that highly expressed HM13 exhibited an association with shorter overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to analyse HM13-related genes, and the data indicated that these genes obviously participated in rRNA processing, ribosome biogenesis, spliceosome, Huntington's disease, and ATP-dependent helicase activity. The Cell Counting Kit-8 (CCK-8) assay and Transwell assay showed that reducing HM13 expression hindered LIHC cell proliferation, migration, and invasion. In conclusion, these findings indicate that HM13 is a biomarker and is related to the poor prognosis of LIHC. Our results are conducive to discovering new targets for LIHC treatment.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Protein Sorting Signals , Histocompatibility , Adenosine Triphosphate
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