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Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. The aim of this work was to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure (ALF) mice before and after hepatic function recovery. In this study, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we showed that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. In addition, fecal microbiota transplantation from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, alterations in synaptic transmission were found in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing 1H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results show that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicate that continuous care may be necessary for monitoring microbial imbalance even in patients with ALF-induced HE whose liver function has recovered significantly.
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Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.
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Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and ß-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Hipocampo , Receptor CB1 de Canabinoide , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Ritmo Circadiano/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Hipocampo/metabolismo , Fígado/metabolismo , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Receptor CB1 de Canabinoide/metabolismo , Traumatismo por Reperfusão/metabolismoRESUMO
(1) Background: Despite the important role choline plays in child development, there are no data on dietary choline intake in early childhood in Australia. (2) Aim: In this cross-sectional study, we estimated the usual total choline intake and the proportion exceeding the Adequate Intake (AI) and determined the main dietary sources of choline in infants 6-12 months (n = 286) and toddlers 12-24 months (n = 475) of age. (3) Methods: A single 24-h food record with repeats collected during the 2021 Australian Feeding Infants and Toddlers Study (OzFITS 2021) was used to estimate dietary choline intake. (4) Results: The mean choline intake was 142 ± 1.9 mg/day in infants and 181 ± 1.2 mg/day in toddlers. Only 35% of infants and 23% of toddlers exceeded the AI for choline based on Nutrient Reference Values (NRVs) for Australia and New Zealand. Breastmilk was the leading source of choline, contributing 42% and 14% of total choline intake in infants and toddlers, respectively; however, egg consumers had the highest adjusted choline intakes and probability of exceeding the AI. (5) Conclusions: Findings suggest that choline intake may be suboptimal in Australian infants and toddlers. Further research to examine the impact of low choline intake on child development is warranted.
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Colina , Fenômenos Fisiológicos da Nutrição do Lactente , Humanos , Lactente , Colina/administração & dosagem , Colina/análise , Austrália , Masculino , Feminino , Estudos Transversais , Pré-Escolar , Dieta/estatística & dados numéricos , Leite Humano/química , Registros de Dieta , Ovos/análise , Desenvolvimento InfantilRESUMO
RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare, highly malignant form of non-Hodgkin lymphoma categorized under the diffuse large B-cell type. It accounts for merely 1% of all non-Hodgkin lymphoma cases and comprises approximately 3% of all brain tumors. The involvement of the cerebellum is observed in only 9% of these cases. Recently, we came across an unusual instance: a young man presenting with multiple lesions located specifically within the cerebellum. PATIENT CONCERNS: A 26-year-old male was admitted to the hospital due to severe headaches. He has a medical history of sporadic headaches, accompanied by dizziness, nausea, and vomiting persisting for a month. Over the last 10 days, his headaches have intensified, coupled with decreased vision and protrusion of the eyeballs. Magnetic resonance imaging (MRI) revealed abnormal signals in both cerebellar hemispheres. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Diagnostic procedures included cerebellar biopsy, posterior fossa decompression, and lateral ventricle drainage. Histopathological examination identified diffuse large B-cell lymphoma (DLBCL) with high proliferative activity. To minimize neurotoxicity, chemotherapy involved intrathecal methotrexate (MTX) injections combined with the CHOP program. The patient has shown good tolerance to the treatment so far. LESSONS: While the definitive optimal treatment approach remains elusive, current chemotherapy centered on high-dose MTX stands as the standard induction therapy. Integrating surgery with radiotherapy and chemotherapy significantly extends patient survival.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Cerebelares , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Adulto , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/terapia , Neoplasias Cerebelares/patologia , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Terapia Combinada , Imageamento por Ressonância Magnética , Cerebelo/patologia , Cerebelo/diagnóstico por imagemRESUMO
Purpose: Quality of life refers to the degree of well-being a person feels. The development of a hemophilia-targeting quality of life scale is important for hemophiliacs and their treating physicians. Methods: Textual analysis. First, a review of studies on quality of life, hemophilia and related quality of life scales was conducted; Subsequently, two rounds of systematic searches of the Springer database were conducted to filter the literature on universal quality of life scale studies and hemophilia-targeting quality of life scale studies by title and abstract, and then textual analysis was performed. Results: The former included 77,456 articles, 26,117 chapters and 7,086 related bibliographies, while the latter initially retrieved 211 entries articles, 118 chapters and 43 related bibliographies. Through filtering, the former contains 22 documents, yielding 1,431 valid word stems, and the latter contains 9 documents, yielding 1,541 valid word stems. Conclusion: While universal quality of life scales mostly fit into the broad framework of WHOQOL- BREF, the development of hemophilia-targeting quality of life scales inclines towards pains that patients suffer and technology advances in pharmaceutical. The current hemophilia QOL scales are mainly based on the HR-QoL, others mainly based on the HR-QoL as the master version. At the same time, the popularization of existing hemophilia quality of life scales in developing countries like China is not high, and the development of hemophilia quality of life scales is insufficient.
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Hemofilia A , Qualidade de Vida , Humanos , Emoções , Hemofilia A/terapiaRESUMO
AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication. METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized. RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus. CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Animais , Camundongos , Acetatos/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disbiose/complicações , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: Social frailty (SF) is associated with multiple adverse health outcomes, yet there has been an inadequate focus on social frailty. The convoy model portrays the social networks through the perspective of the life course, thus providing a framework to explain the occurrence of social frailty. This study aimd to figure out the prevalence of social frailty and loneliness among community-dwelling older adults and to explore their correlations based on convoy model. METHODS: This was a cross-sectional study, and 295 older adults from 10 communities of Zhengzhou in Henan Province participated in the study. Social frailty and loneliness were assessed separately with the Social Frailty Scale and University of California at Los Angeles-Loneliness Scale. The scores of social frailty of the older adults in different characteristic communities were compared by independent sample t-test and single factor analysis of variance. The influencing factors of social frailty were analysed by multiple stepwise linear regression and the structural equation model. The correlation between social frailty and loneliness was analysed by Pearson correlation analysis. RESULTS: The total scores of social frailty and loneliness of the older adults in the community were (2.09 ± 1.53) and (43.19 ± 8.91), respectively. There was a moderate positive correlation between social frailty and loneliness (r = 0.621, P < 0.01). The results of multiple stepwise linear regression analysis showed that age, living styles, balance of payments, and loneliness were the main influencing factors of the social frailty of older adults in the community (F = 27.180, P < 0.001). The structural equation model of social frailty fitted well (χ2 = 47.292, df = 26, χ2/df = 1.819, P = 0.007; RMSEA = 0.053, 95%CI (0.028, 0.076), P = 0.359; GFI = 0.971; AGFI = 0.939; NFI = 0.904; IFI = 0.955; TLI = 0.918; CFI = 0.953; SRMR = 0.0466). CONCLUSIONS: The convoy model had certain applicability in explanation of the relationship between loneliness and social frailty among older adults in community. The incidence of social frailty among the older adults in the community was high, and loneliness was at a medium level. It is necessary to strengthen the intervention of social frailty and loneliness of the older adults in the community, improve the quality of life of the older adults, and promote the development of healthy aging.
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Fragilidade , Solidão , Humanos , Idoso , Vida Independente , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Estudos Transversais , Qualidade de VidaRESUMO
Nano-particles possess desirable attributes such as small particle size, excellent injectivity, and migration performance, making them highly compatible and adaptable for addressing the water flooding requirements of the low-permeability oil reservoir. When selecting an oil displacement agent for enhancing water flooding and improving oil recovery, factors such as injectivity and migration need to be carefully considered. In this study, through a comprehensive analysis of the mechanism and technical characteristics of nano-particle oil displacement agents, the plugging and profile control mechanisms recognized by the mainstream of nano-particles are elucidated. By examining various elements including outcrop fractures, natural micro-fractures, artificial support fractures, and dynamic monitoring data, a reevaluation of the dominant channel scale governing water drive in low permeability reservoirs is conducted, thereby defining the target entities for profile control and flooding operations. Drawing upon Darcy's percolation law and leveraging enhanced oil recovery techniques based on the classical Kozeny equation, a profile control and flooding mechanism is proposed that focuses on increasing the specific surface area of polymer particles while simultaneously reducing reservoir permeability. This innovative approach establishes a novel matching method between nano-polymer particles and the diverse media found within the reservoir. Lastly, the application of nanoparticle flooding technology in Changqing Oilfield is presented, highlighting its practical implementation and benefits.
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Retinal degenerative diseases, characterized by retinal neuronal death and severe vision loss, affect millions of people worldwide. One of the most promising treatment methods for retinal degenerative diseases is to reprogram non-neuronal cells into stem or progenitor cells, which then have the potential to re-differentiate to replace the dead neurons, thereby promoting retinal regeneration. Müller glia are the major glial cell type and play an important regulatory role in retinal metabolism and retinal cell regeneration. Müller glia can serve as a source of neurogenic progenitor cells in organisms with the ability to regenerate the nervous system. Current evidence points toward the reprogramming process of Müller glia, involving changes in the expression of pluripotent factors and other key signaling molecules that may be regulated by epigenetic mechanisms. This review summarizes recent knowledge of epigenetic modifications involved in the reprogramming process of Müller glia and the subsequent changes to gene expression and the outcomes. In living organisms, epigenetic mechanisms mainly include DNA methylation, histone modification, and microRNA-mediated miRNA degradation, all of which play a crucial role in the reprogramming process of Müller glia. The information presented in this review will improve the understanding of the mechanisms underlying the Müller glial reprogramming process and provide a research basis for the development of Müller glial reprogramming therapy for retinal degenerative diseases.
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BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment. METHODS: HIRI murine models were established by ischemia-reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis. RESULTS: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences. CONCLUSIONS: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Hepatopatias , Traumatismo por Reperfusão , Camundongos , Animais , RNA Ribossômico 16S , Metabolismo dos Lipídeos , Hepatopatias/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Disfunção Cognitiva/etiologia , Hipocampo/metabolismo , LipídeosRESUMO
The Slack channel (KCNT1, Slo2.2) is a sodium-activated and chloride-activated potassium channel that regulates heart rate and maintains the normal excitability of the nervous system. Despite intense interest in the sodium gating mechanism, a comprehensive investigation to identify the sodium-sensitive and chloride-sensitive sites has been missing. In the present study, we identified two potential sodium-binding sites in the C-terminal domain of the rat Slack channel by conducting electrophysical recordings and systematic mutagenesis of cytosolic acidic residues in the rat Slack channel C terminus. In particular, by taking advantage of the M335A mutant, which results in the opening of the Slack channel in the absence of cytosolic sodium, we found that among the 92 screened negatively charged amino acids, E373 mutants could completely remove sodium sensitivity of the Slack channel. In contrast, several other mutants showed dramatic decreases in sodium sensitivity but did not abolish it altogether. Furthermore, molecular dynamics (MD) simulations performed at the hundreds of nanoseconds timescale revealed one or two sodium ions at the E373 position or an acidic pocket composed of several negatively charged residues. Moreover, the MD simulations predicted possible chloride interaction sites. By screening predicted positively charged residues, we identified R379 as a chloride interaction site. Thus, we conclude that the E373 site and the D863/E865 pocket are two potential sodium-sensitive sites, while R379 is a chloride interaction site in the Slack channel.SIGNIFICANCE STATEMENT The research presented here identified two distinct sodium and one chloride interaction sites located in the intracellular C-terminal domain of the Slack (Slo2.2, KCNT1) channel. Identification of the sites responsible for the sodium and chloride activation of the Slack channel sets its gating property apart from other potassium channels in the BK channel family. This finding sets the stage for future functional and pharmacological studies of this channel.
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Canais de Potássio Ativados por Sódio , Animais , Ratos , Cloretos/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo , Sódio/metabolismoRESUMO
Chronic Postsurgical Pain (CPSP) is well recognized to impair cognition, particularly memory. Mounting evidence suggests anatomic and mechanistic overlap between pain and cognition on several levels. Interestingly, the drugs currently used for treating chronic pain, including opioids, gabapentin, and NMDAR (N-methyl-D-aspartate receptor) antagonists, are also known to impair cognition. So whether pain-related cognitive deficits have different synaptic mechanisms as those underlying pain remains to be elucidated. In this context, the synaptic transmission in the unsusceptible group (cognitively normal pain rats) was isolated from that in the susceptible group (cognitively compromised pain rats). It was revealed that nearly two-thirds of the CPSP rats suffered cognitive impairment. The whole-cell voltage-clamp recordings revealed that the neuronal excitability and synaptic transmission in the prefrontal cortex and amygdala neurons were enhanced in the unsusceptible group, while these parameters remained the same in the susceptible group. Moreover, the neuronal excitability and synaptic transmission in hippocampus neurons demonstrated the opposite trend. Correspondingly, the levels of synaptic transmission-related proteins demonstrated a tendency similar to that of the excitatory and inhibitory synaptic transmission. Furthermore, morphologically, the synapse ultrastructure varied in the postsynaptic density (PSD) between the CPSP rats with and without cognitive deficits. Together, these observations indicated that basal excitatory and inhibitory synaptic transmission changes were strikingly different between the CPSP rats with and without cognitive deficits.
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Patients with chronic postsurgical pain (CPSP) frequently exhibit comorbid cognitive deficits. Recent observations have emphasized the critical effects of gut microbial metabolites, like short-chain fatty acids (SCFAs), in regulating cognitive function. However, the underlying mechanisms and effective interventions remain unclear. According to hierarchical clustering and 16S rRNA analysis, over two-thirds of the CPSP rats had cognitive impairment, and the CPSP rats with cognitive impairment had an aberrant composition of gut SCFA-producing bacteria. Then, using feces microbiota transplantation, researchers identified a causal relationship between cognitive-behavioral and microbic changes. Similarly, the number of genera that generated SCFAs was decreased in the feces from recipients of cognitive impairment microbiota. Moreover, treatment with the SCFAs alleviated the cognitive-behavioral deficits in the cognitively compromised pain rats. Finally, we observed that SCFA supplementation improved histone acetylation and abnormal synaptic transmission in the medial prefrontal cortex (mPFC), hippocampal CA1, and central amygdala (CeA) area via the ACSS2 (acetyl-CoA synthetase2)-HDAC2 (histone deacetylase 2) axis. These findings link pain-related cognition dysfunction, gut microbiota, and short-chain fatty acids, shedding fresh insight into the pathogenesis and therapy of pain-associated cognition dysfunction.
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Acetato-CoA Ligase , Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Histona Desacetilase 2 , Acetato-CoA Ligase/metabolismo , Animais , Cognição , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Histona Desacetilase 2/metabolismo , Dor Pós-Operatória , RNA Ribossômico 16S , RatosRESUMO
Acute kidney injury (AKI) has been found to be a serious clinical problem with high morbidity and mortality, and is associated with acute inflammatory response and sympathetic activation that subsequently play an important role in the development of AKI. It is well known that the sympathetic nervous system (SNS) and immune system intensely interact and mutually control each other in order to maintain homeostasis in response to stress or injury. Evidence has shown that the superior cervical sympathetic ganglion (SCG) participates in the bidirectional network between the immune and the SNS, and that the superior cervical ganglionectomy has protective effect on myocardial infarction, however, the role of the SCG in the setting of renal ischemic reperfusion injury has not been studied. Here, we sought to determine whether or not the SCG modulates renal ischemic reperfusion (IR) injury in rats. Our results showed that bilateral superior cervical ganglionectomy (SCGx) 14 days before IR injury markedly reduced the norepinephrine (NE) in plasma, and down-regulated the increased expression of tyrosine hydroxylase (TH) in the kidney and hypothalamus. Sympathetic denervation by SCGx in the AKI group increased the level of blood urea nitrogen (BUN) and kidney injury molecule-1 (KIM-1), and exacerbated renal pathological damage. Sympathetic denervation by SCGx in the AKI group enhanced the expression of pro-inflammatory cytokines in plasma, kidney and hypothalamus, and increased levels of Bax in denervated rats with IR injury. In addition, the levels of purinergic receptors, P2X3R and P2X7R, in the spinal cord were up-regulated in the denervated rats of the IR group. In conclusion, these results demonstrate that the sympathetic denervation by SCGx aggravated IR-induced AKI in rats via enhancing the inflammatory response, thus, the activated purinergic signaling in the spinal cord might be the potential mechanism in the aggravated renal injury.
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The diversity and complexity of sympathetic function highlight the importance of fundamental research. Little is known about the interaction of superior cervical sympathetic ganglion (SCG) and gut microbiota. In this study, the engagement of the sympathetic ganglia with gut microbiota was investigated. Bilateral superior cervical ganglionectomy (SCGx) significantly altered the microbiota composition in rats 14 days post-surgery, and these microbiotas may participate in several biological pathways in the host, suggesting the vital role of the cervical sympathetic ganglion in regulating the microbiome-brain axis, and further confirming that the sympathetic nervous system (SNS) regulates the microbiome-brain axis.
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Background: Dual-energy computed tomography (DECT) is used in coronary plaque characterization, myocardial perfusion imaging, and pulmonary embolism diagnosis; however, there is no relevant research on DECT in IgG4-related diseases (IgG4-RD) involving the coronary artery. We are the first to report DECT findings of cardiac morphology and function in IgG4-RD. Patient Findings: Multimodality cardiovascular imaging from a 63-year-old male patient, who presented with IgG4-related pancreatitis, was analyzed. An iodine map and spectral curves were obtained from the DECT, which can help to distinguish between non-calcified plaques and IgG4 lesions of the coronary artery, noninvasive FFRCT (fractional flow reserve derived from coronary computed tomography angiography) and ECV (extracellular volume fraction) demonstrated myocardial ischemia and myocardial fibrosis, respectively. Conclusion: The DECT can detect coronary artery tumor-like lesions caused by IgG4-RD and simultaneously assess the morphological, functional, and histological characteristics of the myocardium. This may help to guide individualized and timely treatment and avoid potentially life-threatening complications.
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In this study, we investigated whether chemical 6-hydroxydopamine (6-OHDA) stimuli caused cardiac sympathetic denervation (SD), and we analyzed gene expression profiles to determine the changes in the lncRNA/circRNAs-miRNA-mRNA network in the affected spinal cord segments to identify putative target genes and molecular pathways in rats with myocardial ischemia-reperfusion injury (MIRI). Our results showed that cardiac sympathetic denervation induced by 6-OHDA alleviated MIRI. Compared with the ischemia reperfusion (IR, MIRI model) group, there were 148 upregulated and 51 downregulated mRNAs, 165 upregulated and 168 downregulated lncRNAs, 70 upregulated and 52 downregulated circRNAs, and 12 upregulated and 11 downregulated miRNAs in the upper thoracic spinal cord of the SD-IR group. Furthermore, we found that the differential genes related to cellular components were mainly enriched in extracellular and cortical cytoskeleton, and molecular functions were mainly enriched in chemokine activity. Pathway analysis showed that the differentially expressed genes were mainly related to the interaction of cytokines and cytokine receptors, sodium ion reabsorption, cysteine and methionine metabolism, mucoglycan biosynthesis, cGMP-PKG signaling pathway, and MAPK signaling pathway. In conclusion, the lncRNA/circRNAs-miRNA-mRNA networks in the upper thoracic spinal cord play an important role in the preventive effect of cardiac sympathetic denervation induced by 6-OHDA on MIRI, which offers new insights into the pathogenesis of MIRI and provides new targets for MIRI.
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Redes Reguladoras de Genes/genética , Traumatismo por Reperfusão Miocárdica/patologia , Oxidopamina/farmacologia , Medula Espinal/metabolismo , Animais , Quimiocinas/metabolismo , Vasos Coronários/cirurgia , Regulação para Baixo/efeitos dos fármacos , Ontologia Genética , Masculino , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Oxidopamina/uso terapêutico , Mapas de Interação de Proteínas/genética , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Simpatectomia , Regulação para Cima/efeitos dos fármacosRESUMO
As an emerging framework in neuroscience, brain connectomics is well suited for investigating key questions on brain complexity by combining viral transneuronal tracing and whole brain graphic methodologies using analytical tools of network science. Transsynaptic viral tract-tracing in the toolbox of neural labeling methods has been a significant development in the connectomics field to decipher the circuit-level architecture of the cerebral cortex. In the present work, we reviewed the current methods enabling structural connectivity from the viscera to the cerebral cortex mapping with viral transneuronal tracers and showed how such neuroanatomic connectomic data could be used to infer new structural and functional information in viscera-cerebral cortex circuits.
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OBJECTIVE: To investigate glucose metabolic alterations in cerebral cortical subareas using 18F-labeled glucose derivative fluorodeoxyglucose (FDG) micro-positron emission tomography (PET) scanning in a rat renal ischemia/reperfusion (RIR) model. METHODS: Small-animal PET imaging in vivo was performed with 18F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR. RESULTS: We found that the average standardized uptake value (SUVaverage) of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group (P<0.05). We also found that glucose uptake in different cortical subregions including the left auditory cortex, right medial prefrontal cortex, right para cortex, left retrosplenial cortex, right retrosplenial cortex, and right visual cortex was significantly increased in the RIR group (P<0.05), but there was no significant difference in the SUVaverage of right auditory cortex, left medial prefrontal cortex, left para cortex, and left visual cortex between the two groups. CONCLUSION: The 18F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.