Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance.

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.

Multimodal magnetic resonance imaging on brain network in amnestic mild cognitive impairment: A mini-review.

Amnestic mild cognitive impairment (aMCI) is a stage between normal aging and Alzheimer disease (AD) where individuals experience a noticeable decline in memory that is greater than what is expected with normal aging, but dose not meet the clinical criteria for AD. This stage is considered a transitional phase that puts individuals at a high risk for developing AD. It is crucial to intervene during this stage to reduce the changes of AD development. Recently, advanced multimodal magnetic resonance imaging techniques have been used to study the brain structure and functional networks in individuals with aMCI. Through the use of structural magnetic resonance imaging, diffusion tensor imaging, and functional magnetic resonance imaging, abnormalities in certain brain regions have been observed in individuals with aMCI. Specifically, the default mode network, salience network, and executive control network have been found to show abnormalities in both structure and function. This review aims to provide a comprehensive understanding of the brain structure and functional networks associated with aMCI. By analyzing the existing literature on multimodal magnetic resonance imaging and aMCI, this study seeks to uncover potential biomarkers and gain insight into the underlying pathogenesis of aMCI. This knowledge can then guide the development of future treatments and interventions to delay or prevent the progression of aMCI to AD.

Magnetic resonance imaging on brain structure and function changes in diabetic peripheral neuropathy.

With the significant increase in the global prevalence of diabetes mellitus (DM), the occurrence of diabetic peripheral neuropathy (DPN) has become increasingly common complication associated with DM. It is particularly in the peripheral nerves of the hands, legs, and feet. DPN can lead to various adverse consequences that greatly affect the quality of life for individuals with DM. Despite the profound impact of DPN, the specific mechanisms underlying its development and progression are still not well understood. Advancements in magnetic resonance imaging (MRI) technology have provided valuable tools for investigating the central mechanisms involved in DPN. Structural and functional MRI techniques have emerged as important methods for studying the brain structures and functions associated with DPN. Voxel-based morphometry allows researchers to assess changes in the volume and density of different brain regions, providing insights into potential structural alterations related to DPN. Functional MRI investigates brain activity patterns, helping elucidate the neural networks engaged during sensory processing and pain perception in DPN patients. Lastly, magnetic resonance spectroscopy provides information about the neurochemical composition of specific brain regions, shedding light on potential metabolic changes associated with DPN. By synthesizing available literature employing these MRI techniques, this study aims to enhance our understanding of the neural mechanisms underlying DPN and contribute to the improvement of clinical diagnosis.

Improvement of autophagic flux mediates the protection of hydrogen sulfide against arecoline-elicited neurotoxicity in PC12 cells.

Arecoline, the most abundant alkaloid of the areca nut, induces toxicity to neurons. Hydrogen sulfide (H2S) is an endogenous gas with neuroprotective effects. We recently found that arecoline reduced endogenous H2S content in PC12 cells. In addition, exogenously administration of H2S alleviated the neurotoxicity of arecoline on PC12 cells. Increasing evidence has demonstrated the neuroprotective role of improvement of autophagic flux. Therefore, the aim of the present work is to explore whether improvement of autophagic flux mediates the protection of H2S against arecoline-caused neurotoxicity. Transmission electron microscope (TEM) for observation of ultrastructural morphology. Western blotting was used to detect protein expression of the related markers. Functional analysis contained LDH release assay, Hoechst 33,258 nuclear staining and flow cytometry were used to detect cytotoxicity and apoptosis. In the present work, we found that arecoline disrupted autophagy flux in PC12 cells as evidenced by accumulation of autophagic vacuoles, increase in LC3II/LC3I, and upregulation of p62 expression in PC12 cells. Notably, we found that sodium hydrosulfide (NaHS), the donor of H2S improved arecoline-blocked autophagy flux in PC12 cells. Furthermore, we found that blocking autophagic flux by chloroquine (CQ), the inhibitor of autophagy flux, antagonized the inhibitory role of NaHS in arecoline-induced cytotoxicity apoptosis and endoplasmic reticulum (ER) stress. In conclusion, H2S improves arecoline-caused disruption of autophagic flux to exert its protection against the neurotoxicity of arecoline.

A bibliometric analysis of neuroimaging biomarkers in Parkinson disease based on Web of Science.

BACKGROUND: This study aimed to analyze and summarize the research hotspots and trends in neuroimaging biomarkers (NMBM) in Parkinson disease (PD) based on the Web of Science core collection database and provide new references for future studies. METHODS: Literature regarding NMBM in PD from 1998 to 2022 was analyzed using the Web of Science core collection database. We utilized CiteSpace software (6.1R2) for bibliometric analyses of countries/institutions/authors, keywords, keyword bursts, references, and their clusters. RESULTS: A total of 339 studies were identified with a continually increasing annual trend. The most productive country and collaboration was the United States. The top research hotspot is PD cognitive disorder. NMBM and artificial intelligence medical imaging have been applied in the clinical diagnosis, differential diagnosis, treatment, and prognosis of PD. The trends in this field include research on T1 weighted structure magnetic resonance imaging in accordance with voxel-based morphometry, PD cognitive disorder, and neuroimaging features of Lewy body dementia and Alzheimer disease. CONCLUSION: The development of NMBM in PD will be effectively promoted by drawing on international research hotspots and cutting-edge technologies, emphasizing international collaboration and institutional cooperation at the national level, and strengthening interdisciplinary research.

Adiponectin Mediates the Protection of H2S Against Chronic Restraint Stress-Induced Cognitive Impairment via Attenuating Hippocampal Damage.

Emerging evidence shows that chronic restraint stress (CRS) can induce cognitive dysfunction, which involves in hippocampal damage. Our recent research reveals that hydrogen sulfide (H2S), a novel gasotransmitter, protects against CRS-induced cognitive impairment, but the underlying mechanism remains unclear. Adiponectin, the most abundant plasma adipokine, has been shown to elicit neuroprotective property and attenuate cognitive impairment. Hence, the present work was aimed to explore whether adiponectin mediates the protective effect of H2S on CRS-induced cognitive impairment by inhibiting hippocampal damage. Results found that administration of Anti-Acrp30, a neutralizing antibody of adiponectin, obviously reverses sodium hydrosulfide (NaHS, an exogenous H2S donor)-induced the inhibition on CRS-induced cognitive impairment according to Y-maze test, Novel object recognition (NOR) test, and Morris water maze (MWM) test. In addition, Anti-Acrp30 blocked the protective effect of NaHS on hippocampal apoptosis in rats-subjected with CRS as evidenced by the pathological changes in hippocampus tissues in hematoxylin and eosin (HE) staining and the increases in the amount of the condensed and stained to yellowish-brown or brownish yellow neuron nucleuses in terminal deoxynucleotidyl transferase transfer-mediated dUTP nick end-labeling (TUNEL) staining as well as the expression of hippocampal pro-apoptotic protein (Bax), and a decrease in the expression of hippocampal anti-apoptotic protein (Bcl-2). Furthermore, Anti-Acrp30 mitigated the inhibitory effect of NaHS on CRS-induced oxidative stress as illustrated by the up-regulation of malondialdehyde (MDA) content and the down-regulation of superoxide dismutase (SOD) activity and glutathione (GSH) level in the hippocampus. Moreover, Anti-Acrp30 eliminated NaHS-induced the reduction of endoplasmic reticulum (ER) stress-related proteins including binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), and Cleaved Caspase-12 expressions in the hippocampus of rats-exposed to CRS. Taken together, these results indicated that adiponectin mediates the protection of H2S against CRS-induced cognitive impairment through ameliorating hippocampal damage.

A highly significant association between Cathepsin S gene polymorphisms rs12068264 and chronic obstructive pulmonary disease susceptibility in Han Chinese population.

Cathepsin S (CTSS) and Sirtuin-1 (SIRT1) played crucial roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the associations between the polymorphisms of CTSS as well as SIRT1 and COPD in Asian population remain elusive. In the present study, one single nucleotide polymorphism (SNP) in rs12068264 was discovered (in 385 individuals) to be associated with the susceptibility of COPD in a Chinese Han population. The genotyping was performed using improved multiplex ligase detection reaction (iMLDR) technique. Subjects with T allele of rs12068264 in CTSS gene had an increased risk of COPD (T compared with C: odds ratio (OR) = 1.351, 95% confidence interval (95% CI): 1.008-1.811, P=0.044) compared with C allele. Subjects with TT genotype at rs12068264 had a higher risk of COPD in a recessive model (TT compared with TC + CC: OR = 2.30, 95% CI: 1.06-4.989, P=0.035). Compared with the C variant of rs12068264, the homozygous carriers of the TT genotype had higher procalcitonin (PCT) levels. Finally, haplotype analysis demonstrated that the SNPs in the CTSS and SIRT1 gene had no statistical differences between patients with COPD and the controls. In conclusion, the genetic polymorphisms of CTSS were associated with the susceptibility of COPD in a Chinese Han population, which may be helpful in understanding genetic mechanisms underlying the pathogenesis of COPD.

MiR-5100 targets TOB2 to drive epithelial-mesenchymal transition associated with activating smad2/3 in lung epithelial cells.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease and the pathogenesis of IPF remains unclear. Our previous study indicated that miR-5100 promotes the proliferation and metastasis of lung epithelial cells. In this study, we investigated the effect and mechanism of miR-5100 on bleomycin (BLM)-induced mouse lung fibrosis and transforming growth factor ß (TGF-ß1) or epidermal growth factor (EGF) induced EMT-model in A549 and Beas-2B cells. The elevated level of miR-5100 was observed in both the mouse lung fibrosis tissues and EMT cell model. Furthermore, the exogenous expression of miR-5100 promoted the EMT-related changes, enhanced TGF-ß1 or EGF-induced EMT and activated the smad2/3 in lung epithelial cells, while silencing miR-5100 had the converse effects. In addition, transwell assay showed that miR-5100 can enhance cell migration. Using target prediction software and luciferase reporter assays, we identified TOB2 as a specific target of miR-5100 and miR-5100 can decrease the accumulation of endogenous TOB2 in A549 and Beas-2B cells. Moreover, the exogenous expression of TOB2 relieves the promotion of miR-5100 on EMT process and migration ability. Taken together, our results indicate that miR-5100 promotes the EMT process by targeting TOB2 associated with activating smad2/3 in lung epithlium cells. Our findings may provide novel insights into the pathogenesis of IPF.

BDNF-TrkB pathway mediates neuroprotection of hydrogen sulfide against formaldehyde-induced toxicity to PC12 cells.

Formaldehyde (FA) is a common environmental contaminant that has toxic effects on the central nervous system (CNS). Our previous data demonstrated that hydrogen sulfide (H2S), the third endogenous gaseous mediator, has protective effects against FA-induced neurotoxicity. As is known to all, Brain-derived neurotropic factor (BDNF), a member of the neurotrophin gene family, mediates its neuroprotective properties via various intracellular signaling pathways triggered by activating the tyrosine kinase receptor B (TrkB). Intriguingly, our previous data have illustrated the upregulatory role of H2S on BDNF protein expression in the hippocampus of rats. Therefore, in this study, we hypothesized that H2S provides neuroprotection against FA toxicity by regulating BDNF-TrkB pathway. In the present study, we found that NaHS, a donor of H2S, upregulated the level of BDNF protein in PC12 cells, and significantly rescued FA-induced downregulation of BDNF levels. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, markedly reversed the inhibition of NaHS on FA-induced cytotoxicity and ablated the protective effects of NaHS on FA-induced oxidative stress, including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA). We also showed that K252a abolished the inhibition of NaHS on FA-induced apoptosis, as well as the activation of caspase-3 in PC12 cells. In addition, K252a reversed the protection of H2S against FA-induced downregulation of Bcl-2 protein expression and upregulation of Bax protein expression in PC12 cells. These data indicate that the BDNF-TrkB pathway mediates the neuroprotection of H2S against FA-induced cytotoxicity, oxidative stress and apoptosis in PC12 cells. These findings provide a novel mechanism underlying the protection of H2S against FA-induced neurotoxicity.