The present study aimed at observing the profile of metabolites in sensitized acupoints induced by myocardial ischemia (MI) and the effect of acupuncture intervention on the changes of the metabolites so as to explore the material basis of acupoint sensitization.A total of 20 New Zealand rabbits were randomly and equally divided into a control group and a model group. The MI model was established by occlusion of the anterior descending branch of the left coronary artery with a controllable air balloon inflation method for 5 min/time, twice a day (4-hours' interval) for continuous 5 days (the first stage of MI). After one day's rest, another 5 days' occlusion was conducted again (the second stage of MI) in the same way. The rabbits of the control group were treated with the same procedures but without occlusion. Subcutaneous microdialysis fluid samples were collected from "Neiguan" (PC 6), "Shenmen" (HT 7), "Xinshu" (BL 15), and "Taixi" (KI 3) regions on day 8(after recovery from operation), 14 (the first stage of MI), and 20 (the second stage of MI), as well as collected from PC 6 region during and post-acupuncture stimulation of PC 6, respectively. Manual acupuncture stimulation was applied to the right PC 6 for 30 min. Partial least squares -linear discriminant analysis (PLS-DA) was used to identify different metabolism patterns of the microdialysis fluid sample between groups and at different time-points in the same one group, and the distinct metabolites as the potential markers between groups were weighted via the values of variable importance in the projection (VIP) in combination with t-test analysis. An area under the curve (AUC) >1.0 indicated a test exhibiting good discrimination between groups.Six metabolites identified to be significantly different between the control and model groups were L-glutamic acid, phenylalanine and 3-hydroxyisobutyric acid (which were significantly increased relevant to the control group), and L-histidine, octadecanedioic acid and 9-keto palmitic acid (significantly decreased relevant to the control group) in the microdialysate of PC 6, HT 7 and BL 15 regions. In the microdialysate of PC 6, 4 metabolites including L-glutamic acid, octadecanedioic acid and 8-isohydroxy PGF 2 α (significantly increased), as well as L-histidine (markedly decreased) were identified to be considerably different between the model and control groups. After acupuncture for 30 min, the AUC level of L-glutamic acid was further significantly increased (P<0.05), that of L-histidine obviously decreased, and those of octadecanedioic acid and 8-isohydroxy PGF 2 α turned back nearly to the level of pre-MI.L-glutamic acid, phenylalanine, 3-hydroxyisobutyric acid, L-histidine, octadecanedioic acid and 9-keto palmitic acid from PC 6, HT 7 and BL 15 regions may be used as the material biomarker for MI-induced sensitization of these acupoints. Manual acupuncture intervention of PC 6 induces a significant change of L-histidine and L-glutamic acid in the local subcutaneous tissues.
Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed to identify one or more factors that may play an important role in the development of CSDH. We enrolled 83 patients with CSDH, including 17 postoperative patients, and analyzed 20 markers in the hematoma fluid and peripheral blood of each patient. Overall differential gene expression was examined to identify the representative markers. The concentration of MMP-8 was significantly lower in the postoperative group than in the preoperative group. The concentration of MMP-9 was significantly higher in the postoperative group than in the preoperative group. These findings indicate that MMP-8 and MMP-9 may play important roles in the pathophysiology of CSDH. Understanding the pathways associated with CSDH may provide insights for improving disease outcomes.
Abstract Objective The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. Methods Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. Results The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. Conclusions Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.
Cortical spreading depression (CSD) has been considered the prominent theory for migraine with aura (MwA). However, it is also argued that CSD can exist in patients in a silent state, and not manifest as aura. Thus, the MwA classification based on aura may be questionable. This study aimed to capture whole-brain connectome-based imaging markers with identifiable signatures for MwA and migraine without aura (MwoA).
Senior citizens suffering from cognitive impairment (CI) are on the East Asia rise. Multiple variables could lead to inter-/intra-individual cognition effectiveness variations, though previous research efforts did not consider weighting issues.
Acrylamide (AA) is widely contaminated in environment and diet. However, the association of AA and sex hormones has rarely been investigated, especially in adolescents, a period of particular susceptibility to sex hormone disruption. In this study, survey-weighted multivariate linear regression models were conducted to determine the association between AA Hb biomarkers [HbAA and glycidamide (HbGA)] and sex hormones [total testosterone (TT) and estradiol (E2)] in a total of 3268 subjects from National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves. Additionally, adult and pubertal mice were treated with AA to assess the effect of AA on sex hormones and to explore the potential mechanisms. Among all the subjects, significant negative patterns for HbGA and sex hormones were identified only in youths (6-19 years old), with the lowest β being - 0.53 (95% CI: -0.80 to -0.26) for TT in males and - 0.58 (95% CI: -0.93 to -0.23) for E2 in females. Stratified analysis further revealed significant negative associations between HbGA and sex hormones in adolescents, with the lowest β being - 0.58 (95% CI: -1.02 to -0.14) for TT in males and - 0.54 (95% CI: -1.03 to -0.04) for E2 in females, while there were no significant differences between children or late adolescents. In mice, the levels of TT and E2 were dramatically reduced in AA-treated pubertal mice but not in adult mice. AA disturbed the expression of genes in the hypothalamic-pituitary-gonadal (HPG) axis, induced apoptosis of hypothalamus-produced gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and reduced serum and hypothalamic GnRH levels in pubertal mice. Our study indicates AA could reduce TT and E2 levels by injuring GnRH neurons and disrupting the HPG axis in puberty, which manifested as severe endocrine disruption on adolescents. Our findings reinforce the idea that adolescence is a vulnerable stage in AA-induced sex hormone disruption.
Abstract Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011–2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR 7 − phthalates : 1.56 and WQS OR 8 − phthalates : 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.
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