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1.
J Pain ; : 104645, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39089662

ABSTRACT

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture group or sham acupuncture group and received 10 sessions of treatment during 4 weeks. The Visual Analog Scale (VAS) for leg pain, Oswestry Disability Index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression (SVR) analyses were performed. Compared to sham acupuncture, acupuncture significantly improved symptoms, including VAS for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus (PoCG). Furthermore, the actual 4-week ODI values were positively correlated with the SVR predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right PoCG may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain.

2.
Immun Inflamm Dis ; 12(8): e1369, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39110067

ABSTRACT

BACKGROUND: The incidence of coronary heart disease (CHD) in youth is rapidly increasing but difficultly recognized in the early stage. METHODS AND RESULTS: In this retrospective study, 194 CHD patients under the age of 45 who previously experienced chest pain symptoms and 170 non-CHD patients were included and demographic data were collected. Systemic inflammation index (SII) and systemic inflammation response index (SIRI) were increased in young CHD patients (p < 001). Spearman's correlation analysis showed that both SII and SIRI were negatively correlated with HDL and positively correlated with hypertension, Gensini score, and hsTnI. Logistic regression analysis indicated that SII and SIRI were independently associated with the presence of CHD in youth with chest pain symptoms. The area under the ROC curve (AUC) of the SII model for young CHD patients was 0.805 (0.728-0.869), and the sensitivity and specificity were 0.65 and 0.823, respectively. Meanwhile, the AUC for the SIRI model was 0.812 (0.739-0.872), and the sensitivity and specificity were 0.673 and 0.8022. The calibration curves of both SII and SIRI models are in good agreement with the actual curves. And the decision curves of both models indicated their clinical practicality. CONCLUSION: SII and SIRI are independent risk factors for CHD in young adults, which can quickly and effectively identify CHD patients among young adults who have previously experienced chest pain symptoms.


Subject(s)
Coronary Disease , Inflammation , Humans , Male , Female , Coronary Disease/immunology , Coronary Disease/epidemiology , Coronary Disease/diagnosis , Coronary Disease/blood , Retrospective Studies , Inflammation/immunology , Inflammation/blood , Inflammation/diagnosis , Adult , Young Adult , ROC Curve , Adolescent , Risk Factors , Chest Pain/immunology , Chest Pain/diagnosis , Chest Pain/epidemiology , Chest Pain/etiology , Biomarkers/blood
3.
BMC Neurol ; 24(1): 199, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872077

ABSTRACT

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.


Subject(s)
Alzheimer Disease , Biomarkers , Cognitive Dysfunction , Gray Matter , Magnetic Resonance Imaging , Humans , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Alzheimer Disease/diagnosis , Male , Female , Aged , Gray Matter/diagnostic imaging , Gray Matter/pathology , Magnetic Resonance Imaging/methods , Middle Aged , Aged, 80 and over , Neuropsychological Tests/statistics & numerical data
4.
Brain Connect ; 14(6): 327-339, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38874973

ABSTRACT

Background and Aims: Previous research has focused on static functional connectivity in gait disorders caused by cerebral small vessel disease (CSVD), neglecting dynamic functional connections and network attribution. This study aims to investigate alterations in dynamic functional network connectivity (dFNC) and topological organization variance in CSVD-related gait disorders. Methods: A total of 85 patients with CSVD, including 41 patients with CSVD and gait disorders (CSVD-GD), 44 patients with CSVD and non-gait disorders (CSVD-NGD), and 32 healthy controls (HC), were enrolled in this study. Five networks composed of 10 independent components were selected using independent component analysis. Sliding time window and k-means clustering methods were used for dFNC analysis. The relationship between alterations in the dFNC properties and gait metrics was further assessed. Results: Three reproducible dFNC states were determined (State 1: sparsely connected, State 2: intermediate pattern, and State 3: strongly connected). CSVD-GD showed significantly higher fractional windows (FW) and mean dwell time (MDT) in State 1 compared with CSVD-NGD. Higher local efficiency variance was observed in the CSVD-GD group compared with HC, but no differences were found in the global efficiency comparison. Both the FW and MDT in State 1 were negatively correlated with gait speed and step length, and the relationship between MDT of State 1 and gait speed was mediated by overall cognition, information processing speed, and executive function. Conclusions: Our study uncovered abnormal dFNC indicators and variations in topological organization in CSVD-GD, offering potential early prediction indicators and freshening insights into the underlying pathogenesis of gait disturbances in CSVD.


Subject(s)
Cerebral Small Vessel Diseases , Gait Disorders, Neurologic , Humans , Cerebral Small Vessel Diseases/physiopathology , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Male , Female , Aged , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/etiology , Middle Aged , Brain/physiopathology , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Magnetic Resonance Imaging/methods , Gait/physiology , Neural Pathways/physiopathology
5.
J Nutr ; 154(7): 1994-2005, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38642744

ABSTRACT

BACKGROUND: The causal nature of gut microbiota and cerebral small vessel disease (CSVD) is still obscure regardless of evidence supporting their observational correlations. OBJECTIVES: The primary objective of this research is to investigate the potentially pathogenic or protective causal impacts of specific gut microbiota on various neuroimaging subtypes of CSVD. METHODS: We obtained the latest summary-level genome-wide databases for gut microbiota and 9 CSVD traits. The univariable and multivariable Mendelian randomization (MR) studies were conducted to examine the possible causal link between exposure and outcome. Meanwhile, we conducted sensitivity analyses sequentially, containing the heterogeneity, pleiotropy, and leave-one-out analysis. Additionally, to clarify the potential bidirectional causality, the causality from CSVD traits to the identified gut microbiota was implemented through reverse MR analysis. RESULTS: The univariable MR analysis identified 22 genetically predicted bacterial abundances that were correlated with CSVD traits. Although conditioning on macronutrient dietary compositions, 2 suggestive relationships were retained using the multivariable MR analysis. Specifically, the class Negativicutes and order Selenomonadales exhibited a negative causal association with strictly lobar cerebral microbleeds, one neuroimaging trait of CSVD. There is insufficient evidence indicating the presence of heterogeneity and horizontal pleiotropy. Furthermore, the identified causal relationship was not driven by any single nucleotide polymorphism. The results of the reverse MR analysis did not reveal any statistically significant causality from CSVD traits to the identified gut microbiota. CONCLUSIONS: Our study indicated several suggestive causal effects from gut microbiota to different neuroimaging subtypes of CSVD. These findings provided a latent understanding of the pathogenesis of CSVD from the perspective of the gut-brain axis.


Subject(s)
Cerebral Small Vessel Diseases , Gastrointestinal Microbiome , Mendelian Randomization Analysis , Cerebral Small Vessel Diseases/genetics , Cerebral Small Vessel Diseases/microbiology , Humans , Genome-Wide Association Study
6.
Inorg Chem ; 63(10): 4487-4491, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38416696

ABSTRACT

We herein report an unprecedented organic-inorganic hybrid borate incorporating a novel nonlinear-optical (NLO) active unit, namely, [C(NH2)3][B(C2O2H4)2]. The novel NLO active unit was derived from the condensation reaction between two glycol molecules and one (BO4)5- group. The title compound exhibits a moderate second-harmonic-generation effect (0.7 × KDP), a significant band gap (5.76 eV), and a suitable birefringence (0.078 at 550 nm). The optical properties are determined by the synergistic interaction between the C(NH2)3+ cation and the [B(C2O2H4)2]- group, as indicated by theoretical calculations.

7.
Inorg Chem ; 63(8): 3948-3954, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38350031

ABSTRACT

The key to searching novel nonlinear optical (NLO) crystals was effectively combining the NLO-active units to obtain a noncentrosymmetric structure. Nevertheless, the present predicament lies in the growing challenge of discovering novel crystals within conventional inorganic frameworks that surpass the properties of the current NLO materials. In view of this, researchers expanded their research focus to the organic-inorganic hybridization system; it is foreseeable to concentrate the advantages from several kinds of NLO-active units to acquire novel NLO crystals with superior properties. We herein report an organic-inorganic hybrid molybdate crystal, namely, [C(NH2)3]6Mo7O24 (GMO). It was successfully obtained via combining inorganic NLO-active MoO6 octahedra and organic π-conjugated [C(NH2)3]+ groups. GMO demonstrates a moderate second-harmonic-generation response, specifically measuring about 1.3 times the value of KDP. Additionally, it exhibits a significant birefringence value of 0.203 at the wavelength of 550 nm and possesses a wide band gap of 3.31 eV. Theoretical calculations suggest that the optical properties of the GMO are primarily influenced by the synergy effect of [C(NH2)3]+ groups between MoO6 octahedra.

8.
Immun Ageing ; 20(1): 66, 2023 Nov 21.
Article in English | MEDLINE | ID: mdl-37990246

ABSTRACT

BACKGROUND: CircZBTB46 has been identified as being associated with the risk of coronary artery disease (CAD) and has the potential to be a diagnostic biomarker for CAD. However, the specific function and detailed mechanism of circZBTB46 in CAD are still unknown. METHODS: The expression levels and properties of circRNAs were examined using qRT‒PCR, RNA FISH, and subcellular localization analysis. ApoE-/- mice fed a high-fat diet were used to establish an atherosclerosis model. HE, Masson, and Oil Red O staining were used to analyze the morphological features of the plaque. CCK-8, Transwell, and wound healing assays, and flow cytometric analysis were used to evaluate cell proliferation, migration, and apoptosis. RNA pull-down, silver staining, mass spectrometry analysis, and RNA-binding protein immunoprecipitation (RIP) were performed to identify the interacting proteins of circZBTB46. RESULTS: CircZBTB46 is highly conserved and is significantly upregulated in atherosclerotic lesions. Functional studies revealed that knockdown of circZBTB46 significantly decreased the atherosclerotic plaque area, attenuating the progression of atherosclerosis. In addition, silencing circZBTB46 inhibited cell proliferation and migration and induced apoptosis. Mechanistically, circZBTB46 physically interacted with hnRNPA2B1 and suppressed its degradation, thereby regulating cell functions and the formation of aortic atherosclerotic plaques. Additionally, circZBTB46 was identified as a functional mediator of PTEN-dependent regulation of the AKT/mTOR signaling pathway and thus affected cell proliferation and migration and induced apoptosis. CONCLUSION: Our study provides the first direct evidence that circZBTB46 functions as an important regulatory molecule for CAD progression by interacting with hnRNPA2B1 and regulating the PTEN/AKT/mTOR pathway.

9.
iScience ; 26(11): 108103, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37867960

ABSTRACT

DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

10.
J Neurosci Res ; 101(11): 1711-1727, 2023 11.
Article in English | MEDLINE | ID: mdl-37469210

ABSTRACT

White matter hyperintensities (WMHs) of presumed vascular origin are important imaging biomarkers of cerebral small vessel disease (CSVD). Previous studies have verified abnormal functional brain networks in CSVD. However, most of these studies rely on static functional connectivity, and only a few focus on the varying severity of the WMHs. Hence, our study primarily explored the disrupted dynamic functional network connectivity (dFNC) and topological organization variance in patients with WMHs. This study included 38 patients with moderate WMHs, 47 with severe WMHs, and 68 healthy controls (HCs). Ten independent components were chosen using independent component analysis based on resting-state functional magnetic resonance imaging. The dFNC of each participant was estimated using sliding windows and k-means clustering. We identified three reproducible dFNC states. Among them, patients with WMHs had a significantly higher occurrence in the sparsely connected State 1, but a lower occurrence and shorter duration in the positive and stronger connected State 3. Regarding topological organization variance, patients with WMHs showed higher variance in local efficiency but not global efficiency compared to HCs. Among the WMH subgroups, patients with severe WMHs showed similar but more obvious alterations than those with moderate WMHs. These altered network characteristics indicated an imbalance between the functional segregation and integration of brain networks, which was correlated with global cognition, memory, executive functions, and visuospatial abilities. Our study confirmed aberrant dFNC state metrics and topological organization variance in patients with moderate-to-severe WMHs; thus, it might provide a new pathway for exploring the pathogenesis of cognitive impairment.


Subject(s)
White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Magnetic Resonance Imaging/methods , Brain/pathology , Cognition , Executive Function
11.
Psychol Res Behav Manag ; 16: 2059-2069, 2023.
Article in English | MEDLINE | ID: mdl-37305222

ABSTRACT

Background: Pro-environmental behavior necessitates individuals to make personal sacrifices, such as spending more money on environmentally-friendly products to benefit the environment. Realistically, individuals may not be willing to engage in pro-environmental behavior based self-interest. The increase in personal pro-environmental behavior has become an urgent issue in the field of environmental psychology. Purpose: The present study adopted green consumption paradigm to explore the internal mechanisms of pro-environmental behavior at different personal costs, the role of social and personal norms on pro-environmental behavior, which can promote individual pro-environmental behavior. Methods: In our experiment, participants first were instructed to read texts unrelated and related to social norms in sequence. Participants subsequently completed the product choice task, which involved making choices between buying green (eco-friendly) products or cheaper (self-interested) common products, a method to measure pro-environment behavior. Finally, the participants completed the personal norms scale and social norms check. Results: The findings of present study indicated that pro-environmental behavior decreased as personal costs increased. However, social norms effectively promoted individuals' pro-environmental behavior, and personal norms played a mediating role at high personal costs. Conclusion: Our findings indicate that individuals tend to choose cheaper common products that are harmful to the natural environment in self-interest. However, we discuss the implications for the use of social norms as a social marketing technique, which extends the Norm Activation Model.

12.
Inorg Chem ; 62(12): 4757-4761, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-36916671

ABSTRACT

We herein report a mixed organic cationic hybrid nitrate, namely, [C(NH2)2NHNO2][C(NH2)3](NO3)2 (1). It was successfully achieved via combining three different planar groups: [(C(NH2)2NHNO2]+, C(NH2)3+, and NO3-. First-principles calculations confirm that the [(C(NH2)2NHNO2]+ group is an excellent cationic nonlinear-optical (NLO)-active unit. The title compound exhibits a moderate second-harmonic-generation (SHG) response (1.5 × KDP), a wide band gap (3.58 eV), and a suitable birefringence of 0.071 at 550 nm. Theoretical calculations indicate that the synergy effect between the [(C(NH2)2NHNO2]+ and C(NH2)3+ groups dominates the SHG process.

13.
Planta ; 257(4): 71, 2023 Mar 02.
Article in English | MEDLINE | ID: mdl-36862199

ABSTRACT

MAIN CONCLUSIONS: STD1 specifically interacts with MAP65-5 in rice and they cooperatively control microtubule bundles in phragmoplast expansion during cell division. Microtubules play critical roles during the cell cycle progression in the plant cell. We previously reported that STEMLESS DWARF 1 (STD1), a kinesin-related protein, was localized specifically to the phragmoplast midzone during telophase to regulate the lateral expansion of phragmoplast in rice (Oryza sativa). However, how STD1 regulates microtubule organization remains unknown. Here, we found that STD1 interacted directly with MAP65-5, a member of the microtubule-associated proteins (MAPs). Both STD1 and MAP65-5 could form homodimers and bundle microtubules individually. Compared with MAP65-5, the microtubules bundled by STD1 were disassembled completely into single microtubules after adding ATP. Conversely, the interaction of STD1 with MAP65-5 enhanced the microtubule bundling. These results suggest STD1 and MAP65-5 might cooperatively regulate microtubule organization in the phragmoplast at telophase.


Subject(s)
Microtubule-Associated Proteins , Oryza , Microtubule-Associated Proteins/genetics , Kinesins , Microtubules , Mitosis
14.
Inorg Chem ; 62(4): 1323-1327, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36657021

ABSTRACT

Herein, we report an unprecedented asymmetric guanidinium polyiodate, namely, C(NH2)3(I3O8)(HI3O8)(H2I2O6)(HIO3)4·3H2O (1). The title compound was obtained via the hybridization of polyiodate anions and planar π-conjugated C(NH2)3+; meanwhile, its strong second-harmonic-generation (SHG) response (2.1 × KDP, where KDP = KH2PO4) and wide band gap (3.89 eV) were mainly dominated by the synergy effect of the aforementioned structural units.

15.
Front Neurosci ; 16: 1036487, 2022.
Article in English | MEDLINE | ID: mdl-36532276

ABSTRACT

Introduction: Sciatica is a pain disorder often caused by the herniated disk compressing the lumbosacral nerve roots. Neuroimaging studies have identified functional abnormalities in patients with chronic sciatica (CS). However, few studies have investigated the neural marker of CS using brain structure and the classification value of multidimensional neuroimaging features in CS patients is unclear. Methods: Here, structural and resting-state functional magnetic resonance imaging (fMRI) was acquired for 34 CS patients and 36 matched healthy controls (HCs). We analyzed cortical surface area, cortical thickness, amplitude of low-frequency fluctuation (ALFF), regional homogeneity (REHO), between-regions functional connectivity (FC), and assessed the correlation between neuroimaging measures and clinical scores. Finally, the multimodal neuroimaging features were used to differentiate the CS patients and HC individuals by support vector machine (SVM) algorithm. Results: Compared to HC, CS patients had a larger cortical surface area in the right banks of the superior temporal sulcus and rostral anterior cingulate; higher ALFF value in the left inferior frontal gyrus; enhanced FCs between somatomotor and ventral attention network. Three FCs values were associated with clinical pain scores. Furthermore, the three multimodal neuroimaging features with significant differences between groups and the SVM algorithm could classify CS patients and HC with an accuracy of 90.00%. Discussion: Together, our findings revealed extensive reorganization of local functional properties, surface area, and network metrics in CS patients. The success of patient identification highlights the potential of using artificial intelligence and multimodal neuroimaging markers in chronic pain research.

16.
Brain Sci ; 12(11)2022 Nov 06.
Article in English | MEDLINE | ID: mdl-36358431

ABSTRACT

The application of voxel-mirrored homotopic connectivity (VMHC) analysis to study the central mechanism of migraine has been limited. Furthermore, little is known about inter-hemispheric functional connectivity (FC) alterations during resting state in female patients with migraine. This study aimed to investigate potential interictal VMHC impairments in migraine without aura (MwoA) patients and the relationship between connectivity alterations and clinical parameters. Resting-state functional magnetic resonance imaging data and clinical information were acquired from 43 female MwoA patients and 43 matched healthy controls. VMHC analysis was used to compare differences between these two groups, and brain regions showing significant differences were chosen as a mask to perform a seed-based FC group comparison. Subsequent correlation analysis was conducted to explore the relationship between abnormal inter-hemispheric FC and clinical data. Compared with healthy controls, female MwoA patients revealed significantly decreased VMHC in the bilateral cerebellum; cuneus; and lingual, middle occipital, precentral and postcentral gyri. Seed-based FC analysis indicated disrupted intrinsic connectivity in the cerebellum, and default mode, visual and sensorimotor network. These VMHC and FC abnormalities were negatively correlated with clinical indexes including duration of disease, migraine days and visual analogue scale. These inter-hemispheric FC impairments and correlations between abnormal VMHC and FC and clinical scores may improve our understanding of the central mechanism of female-specific migraine.

17.
Development ; 149(17)2022 09 01.
Article in English | MEDLINE | ID: mdl-35929537

ABSTRACT

Mutations that occur in RNA-splicing machinery may contribute to hematopoiesis-related diseases. How splicing factor mutations perturb hematopoiesis, especially in the differentiation of erythro-myeloid progenitors (EMPs), remains elusive. Dhx38 is a pre-mRNA splicing-related DEAH box RNA helicase, for which the physiological functions and splicing mechanisms during hematopoiesis currently remain unclear. Here, we report that Dhx38 exerts a broad effect on definitive EMPs as well as the differentiation and maintenance of hematopoietic stem and progenitor cells (HSPCs). In dhx38 knockout zebrafish, EMPs and HSPCs were found to be arrested in mitotic prometaphase, accompanied by a 'grape' karyotype, owing to the defects in chromosome alignment. Abnormal alternatively spliced genes related to chromosome segregation, the microtubule cytoskeleton, cell cycle kinases and DNA damage were present in the dhx38 mutants. Subsequently, EMPs and HSPCs in dhx38 mutants underwent P53-dependent apoptosis. This study provides novel insights into alternative splicing regulated by Dhx38, a process that plays a crucial role in the proliferation and differentiation of fetal EMPs and HSPCs.


Subject(s)
Alternative Splicing , Zebrafish , Alternative Splicing/genetics , Animals , Hematopoiesis/genetics , Hematopoietic Stem Cells , Myeloid Progenitor Cells , Zebrafish/genetics , Zebrafish/metabolism
18.
Oncogene ; 41(29): 3694-3704, 2022 07.
Article in English | MEDLINE | ID: mdl-35732801

ABSTRACT

Ewing sarcoma breakpoint region 1 (EWSR1) is a member of FET (FUS/EWSR1/TAF15) RNA-binding family of proteins. The Ewing sarcoma oncoprotein EWS-FLI1 has been extensively studied, while much less is known about EWSR1 itself, especially the potential role of EWSR1 in response to DNA damage. Here, we found that UV irradiation induces acetylation of EWSR1, which is required for its nucleoli translocation. We identified K423, K432, K438, K640, and K643 as the major acetylation sites, p300/CBP and HDAC3/HDAC10 as the major acetyltransferases and deacetylases, respectively. Mechanically, UV-induced EWSR1 acetylation repressed its interaction with spliceosomal component U1C, which caused abnormal splicing of CHK2, suppressing the activity of CHK2 in response to UV irradiation. Taken together, our findings uncover acetylation as a novel regulatory modification of EWSR1, and is essential for its function in DNA damage response.


Subject(s)
Checkpoint Kinase 2 , DNA Damage , RNA-Binding Protein EWS , Sarcoma, Ewing , Acetylation , Alternative Splicing/genetics , Checkpoint Kinase 2/genetics , Checkpoint Kinase 2/metabolism , DNA Damage/genetics , DNA Damage/physiology , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Humans , Oncogene Proteins, Fusion/genetics , Protein Transport/genetics , Protein Transport/physiology , RNA-Binding Protein EWS/genetics , RNA-Binding Protein EWS/metabolism , Sarcoma, Ewing/genetics
19.
Antioxidants (Basel) ; 11(2)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35204083

ABSTRACT

Although essential for life, copper is also potentially toxic in concentrations that surpass physiological thresholds. The high-osmolarity glycerol pathway of yeast is the main regulator of adaptive responses and is known to play crucial roles in the responses to various stressors. The objective of this research is to determine whether the HOG pathway could be activated and to investigate the possible interplay of the HOG pathway and oxidative stress due to copper exposure. In this research, we demonstrate that copper could induce oxidative stress, including the elevated concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA). Increased combination with GSH, increased intracellular SOD activity, and the up-regulation of relevant genes can help cells defend themselves against oxidative toxicity. The results show that copper treatment triggers marked and prolonged Hog1 phosphorylation. Significantly, oxidative stress generated by copper toxicity is essential for the activation of Hog1. Activated Hog1 is translocated to the nucleus to regulate the expressions of genes such as CTT1, GPD1, and HSP12, among others. Furthermore, copper exposure induced significant G1-phase cell cycle arrest, while Hog1 partially participated in the regulation of cell cycle progression. These novel findings reveal another role for Hog1 in the regulation of copper-induced cellular stress.

20.
J Food Prot ; 85(1): 104-111, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34265056

ABSTRACT

ABSTRACT: Diseases caused by harmful microorganisms pose a serious threat to human health. Safe and environmentally friendly disinfectants are, therefore, essential in preventing and controlling such pathogens. This study aimed to investigate the antimicrobial activity and mechanism of a novel hydrogen peroxide and silver (H2O2-Ag+) complex (HSC) in combatting Staphylococcus aureus ATCC 29213, Escherichia coli O157:H7 NCTC 12900, and Salmonella Typhimurium SL 1344. The MICs and MBCs against S. aureus were found to be 0.014% H2O2-3.125 mg/L Ag+, and for both E. coli O157:H7 and Salmonella Typhimurium they were 0.028% H2O2-6.25 mg/L Ag+. Results of the time-kill trial suggest that HSC could inhibit the growth of the tested bacteria, because 99.9% of viable cells were killed following treatment at 1 MIC for 3 h. The mechanism of antibacterial action of HSC was found to include the disruption of the bacterial cell membrane, followed by reduction of intracellular ATP concentration and inhibition of the activity of antioxidases, superoxide dismutase, and catalase. The enhanced bactericidal effect of hydrogen peroxide combined with silver indicates a potential for its application in environmental disinfection, particularly in the food industry.


Subject(s)
Disinfectants , Escherichia coli O157 , Colony Count, Microbial , Disinfectants/pharmacology , Food Microbiology , Humans , Hydrogen Peroxide/pharmacology , Salmonella typhimurium , Staphylococcus aureus
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