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"Li, Zhi-Hua"
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Top-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex
Spinal sensory transmission is under descending biphasic modulation, and descending facilitation is believed to contribute to chronic pain. Descending modulation from the brainstem rostral ventromedial medulla (RVM) has been the most studied, whereas little is known about direct corticospinal modulation. Here, we found that stimulation in the anterior cingulate cortex (ACC) potentiated spinal excitatory synaptic transmission and this modulation is independent of the RVM. Peripheral nerve injury enhanced the spinal synaptic transmission and occluded the ACC-spinal cord facilitation. Inhibition of ACC reduced the enhanced spinal synaptic transmission caused by nerve injury. Finally, using optogenetics, we showed that selective activation of ACC-spinal cord projecting neurons caused behavioral pain sensitization, while inhibiting the projection induced analgesic effects. Our results provide strong evidence that ACC stimulation facilitates spinal sensory excitatory transmission by a RVM-independent manner, and that such top-down facilitation may contribute to the process of chronic neuropathic pain.
It is known that descending facilitation of spinal responses may contribute to chronic pain, however many studies have focussed on brainstem mechanisms. Here the authors show that stimulation of the anterior cingulate cortex increases excitatory transmission in the dorsal horn, and that this may be via a direct pathway independent of the brainstem.
Journal Article
Chronic Exposure to Tributyltin Induces Brain Functional Damage in Juvenile Common Carp (Cyprinus carpio)
The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.
Journal Article
Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium
Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF‐1α, Tβ4, VEGF and SDF‐1 expression and decreased CXCL14 expression in hypoxic and serum‐deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF‐1α, Tβ4, VEGF, SDF‐1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial‐derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c‐kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
Journal Article
Suppression of migration and invasion by taraxerol in the triple-negative breast cancer cell line MDA-MB-231 via the ERK/Slug axis
As one of the triterpene extracts of Taraxacum, a traditional Chinese plant, taraxerol (TRX) exhibits antitumor activity. In this study, we evaluated the effects of TRX on the migration and invasion of MDA-MB-231 cells, analyzed the molecular mechanism through network pharmacology and molecular docking, and finally verified it by in vitro experiments. The results showed that TRX could inhibit the migration and invasion of MDA-MB-231 cells in a time- and concentration-dependent manner, while MAPK3 was the most promising target and could stably combine with TRX. In addition, the relative protein expression levels were detected by Western blot, and we observed that TRX could inhibit the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. Moreover, an ERK activator (tert-butylhydroquinone, tBHQ) partially reversed the suppressive effect of TRX on MDA-MB-231 cells. In conclusion, TRX inhibited the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis.
Journal Article
Development and validation of a nomogram for breast cancer-related lymphedema
To establish and validate a predictive model for breast cancer-related lymphedema (BCRL) among Chinese patients to facilitate individualized risk assessment. We retrospectively analyzed data from breast cancer patients treated at a major single-center breast hospital in China. From 2020 to 2022, we identified risk factors for BCRL through logistic regression and developed and validated a nomogram using R software (version 4.1.2). Model validation was achieved through the application of receiver operating characteristic curve (ROC), a calibration plot, and decision curve analysis (DCA), with further evaluated by internal validation. Among 1485 patients analyzed, 360 developed lymphedema (24.2%). The nomogram incorporated body mass index, operative time, lymph node count, axillary dissection level, surgical site infection, and radiotherapy as predictors. The AUCs for training (N = 1038) and validation (N = 447) cohorts were 0.779 and 0.724, respectively, indicating good discriminative ability. Calibration and decision curve analysis confirmed the model’s clinical utility. Our nomogram provides an accurate tool for predicting BCRL risk, with potential to enhance personalized management in breast cancer survivors. Further prospective validation across multiple centers is warranted.
Journal Article
Alterations in Hypothalamus-Pituitary-Adrenal/Thyroid Axes and Gonadotropin-Releasing Hormone in the Patients with Primary Insomnia: A Clinical Research
The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the \"stepwise\" method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.
Journal Article
Toxicity evaluation of triphenyltin in zebrafish larvae by embryonic malformation, retinal development, and GH/IGF axis
The adverse influences of triphenyltin (TPT) on the aquatic system have been of great concern due to their widespread use and ubiquity in water environment, although it has been prohibited as antifouling coatings. In the present study, we investigated the developmental toxicity of TPT on zebrafish embryos by exposure to different concentrations (0, 1, 10, and 100 ng/l) from 2-h post-fertilization (hpf). Some parameters of developmental abnormalities (hatching, survival, body length, and malformation) were recorded, as well as the expression of several genes involved in the retinal development and growth hormone/insulin-like growth factor (GH/IGF) axis. Our results showed that TPT exposure induced developmental toxicity, including growth inhibition, malformation, and the dysregulation of gene expression levels related to the retinal development and GH/IGF axis. Thus, our data indicated that environmental exposure of TPT could induce developmental toxicity in zebrafish embryos, and those parameters could extend our understanding of the adverse effects of TPT on aquatic organisms.
Journal Article
Physiological Function Disturbances and Adaptive Responses in Nile Tilapia (Oreochromis niloticus) Under Different Salinity Stresses
The physiological functions of aquatic organisms are closely linked to changes in environmental salinity. High-salinity environments can disrupt energy metabolism, induce inflammation, and negatively impact normal growth and development. However, aquatic organisms possess self-regulatory mechanisms that can mitigate these impacts to some extent. This study aimed to investigate the adaptive regulatory processes in Nile tilapia (Oreochromis niloticus, Linnaeus, 1758) exposed to high-salinity environments by evaluating metabolic enzyme activities and levels of inflammatory markers. The increased levels of IL-1β and elevated ACP activity suggested that high-salinity conditions (15 and 30 ppt) induced intestinal inflammation. Concurrently, the elevated activities of SOD and GSH, along with decreased SDH activity, pointed to heightened oxidative stress in the brain and a reduced mitochondrial energy supply. Additionally, the adaptive features of intestinal energy metabolism under high-salinity conditions were evident, with adjustments in HK and PK activities mitigating the effects of suppressed PFK activity. Moreover, elevated lipase (LPS) activity in muscle tissue under salinity stress indicated that fat is mobilized to supply energy for muscle activity without affecting muscle protein. In conclusion, salinity stress triggered inflammatory and oxidative stress responses in Nile tilapia, yet the fish exhibited self-regulatory processes in energy metabolism. This study provides a theoretical basis for understanding the adaptive mechanisms of aquatic organisms in stressful environments.
Journal Article
Tributyltin Induces the Tissue-Specific Stresses in Zebrafish, a Study in Various Tissues of Muscle, Gill and Intestine
Because the mechanism of tissue-specific toxicity of tributyltin (TBT) in aquatic organisms has not been explained clearly, the aim of this study is to investigate the effect of chronic exposure to TBT on muscle-related energy metabolism, gill-related ATPase enzymatic system and intestine-related digestive enzymes activities in zebrafish. Male zebrafish were exposed to sub-lethal concentrations of TBT (10, 100 and 300 ng/L) for 6 weeks. Multiple biomarkers were measured (such as glucose, lactate, hexokinase, pyruvate kinase, lactate dehydrogenase, ATP content, ATPases, trypsin, lipase and amylase), which reflected more serious physiological stress with increasing TBT concentrations during the experimental period. Through principal component analysis (PCA) and integrated biomarker response (IBR) analysis, the toxic effect of TBT in zebrafish was in a concentration-dependent manner. Shortly, the results of this study can provide new evidence for a comprehensive understanding of the toxic effects of TBT.
Journal Article