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1.
iScience ; 26(10): 107792, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37720090

ABSTRACT

Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.

2.
Heliyon ; 9(6): e16833, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37303570

ABSTRACT

Background: Although commonly used for the treatment of descending aortic dissection, endovascular repair is challenging for ascending aortic pseudoaneurysms. Rapid ventricular pacing (RVP), a method that temporarily impedes cardiac output by stopping ventricular activity, heralds potential benefits for thoracic endovascular aortic repair (TEVAR) during precision landing. Recently, we successfully treated an anastomosis pseudoaneurysm after the Bentall procedure using TEVAR assisted by RVP. Case report: A 69-year-old male was admitted to our hospital with a ascending aortic anastomosis pseudoaneurysm. He had undergone a Bentall procedure and a coronary artery bypass grafting nine years prior. After extensive consultation, the decision was made to perform TEVAR with the assistance of RVP. After a covered stent graft was delivered to the precise location of the ascending aorta, RVP was performed at a frequency of 180 beats/min with a pacemaker. When a flattened arterial blood wave of <50 mmHg was observed, the stent graft was released precisely between the opening of the coronary graft and innominate artery. Angiography revealed the presence of an endoleak; therefore, a set of interlock coils were packed into the aneurysm. Subsequent angiography showed intact blood flow in the aorta, superior arch branches, and coronary graft vessels. The patient recovered uneventfully after the procedure. He was discharged six days later and was doing well at the eight-month follow-up. Conclusion: The case indicates that TEVAR assisted by RVP is a promising combination for ascending aortic pseudoaneurysm in selected patients.

3.
J Mol Neurosci ; 71(1): 55-65, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32557241

ABSTRACT

A variety of studies have proposed that transient receptor potential vanilloid 1 (TRPV1) is involved in the progression of multiple diseases, including neuropathic pain. Although increased expression of TRPV1 in chronic constriction injury was described earlier, the underlying regulatory mechanisms of TRPV1 in neuropathic pain remain largely unknown. In our study, we constructed a chronic constriction injury (CCI) rat model to deeply analyze the mechanisms underlying TRPV1. RT-qPCR-indicated TRPV1 mRNA and protein expression were extremely upregulated in CCI rat dorsal spinal cord tissues. Then, TRPV1 was corroborated to interact with N-terminal EF-hand Ca2+-binding protein 2 (NECAB2). The mRNA and protein levels of NECAB2 were increased in CCI tissues. Moreover, TRPV1 and NECAB2 together regulated nociceptive procession-associated protein metabotropic glutamate receptor 5 (mGluR5), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and Ca2+ in isolated microglia of CCI rats. Moreover, TRPV1 upregulation apparently increased mechanical allodynia and thermal hyperalgesia as well as the expression of inflammation-associated genes (COX-2, TNF-α, and IL-6). In addition, downregulation of NECAB2 significantly decreased mechanical allodynia and thermal hyperalgesia as well as the expression of COX-2, TNF-α, and IL-6. Furthermore, TRPV1 was confirmed to be a downstream target of miR-338-3p. TRPV1 overexpression abolished the inhibitory effect by miR-338-3p elevation on neuropathic pain development. In summary, this study proved TRPV1, targeted by miR-338-3p, induced neuropathic pain by interacting with NECAB2, which provides a potential therapeutic target for neuropathic pain treatment.


Subject(s)
Calcium-Binding Proteins/physiology , MicroRNAs/genetics , Nerve Tissue Proteins/physiology , Neuralgia/physiopathology , TRPV Cation Channels/physiology , Animals , Calcium Signaling , Calcium-Binding Proteins/biosynthesis , Calcium-Binding Proteins/genetics , Cell Line, Tumor , Cyclooxygenase 2/biosynthesis , Cyclooxygenase 2/genetics , Gene Expression Regulation , Humans , Hyperalgesia/physiopathology , Inflammation , Interleukin-6/biosynthesis , Interleukin-6/genetics , MAP Kinase Signaling System , Male , Microglia/metabolism , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Neuralgia/genetics , PC12 Cells , Pain Threshold/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Receptor, Metabotropic Glutamate 5/physiology , Recombinant Proteins/metabolism , Sciatic Neuropathy/complications , Sciatica/etiology , Sciatica/genetics , Sciatica/physiopathology , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord/physiopathology , TRPV Cation Channels/antagonists & inhibitors , TRPV Cation Channels/biosynthesis , TRPV Cation Channels/genetics , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/genetics , Up-Regulation
4.
Front Pediatr ; 8: 522, 2020.
Article in English | MEDLINE | ID: mdl-33014927

ABSTRACT

Background: The mortality prediction scores were widely used in pediatric intensive care units. However, their performances were unclear in Chinese patients and there were also no reports based on large sample sizes in China. This study aims to evaluate the performances of three existing severity assessment scores in predicting PICU mortality and to identify important determinants. Methods: This prospective observational cohort study was carried out in eight multidisciplinary, tertiary-care PICUs of teaching hospitals in China. All eligible patients admitted to the PICUs between Aug 1, 2016, and Jul 31, 2017, were consecutively enrolled, among whom 3,957 were included for analysis. We calculated PCIS, PRISM IV, and PELOD-2 scores based on patient data collected in the first 24 h after PICU admission. The in-hospital mortality was defined as all-cause death within 3 months after admission. The discrimination of mortality was assessed using the area under the receiver-operating characteristics curve (AUC) and calibrated using the Hosmer-Lemeshow goodness-of-fit test. Results: A total of 4,770 eligible patients were recruited (median age 18.2 months, overall mortality rate 4.7%, median length of PICU stay 6 days), and 3,957 participants were included in the analysis. The AUC (95% confidence intervals, CI) were 0.74 (0.71-0.78), 0.76 (0.73-0.80), and 0.80 (0.77-0.83) for PCIS, PRISM IV, and PELOD-2, respectively. The Hosmer-Lemeshow test gave a chi-square of 3.16 for PCIS, 2.16 for PRISM IV and 4.81 for PELOD-2 (p ≥ 0.19). Cox regression identified five predictors from the items of scores better associated with higher death risk, with a C-index of 0.83 (95%CI 0.79-0.86), including higher platelet (HR = 1.85, 95% CI 1.59-2.16), invasive ventilation (HR = 1.40, 1.26-1.55), pupillary light reflex (HR = 1.31, 95% CI 1.22-1.42) scores, lower pH (HR 0.89, 0.84-0.94), and extreme PaO2 (HR 2.60, 95% CI 1.61-4.19 for the 1st quantile vs. 4th quantile) scores. Conclusions: Performances of the three scores in predicting PICU mortality are comparable, and five predictors were identified with better prediction to PICU mortality in Chinese patients.

5.
Cell Mol Biol Lett ; 23: 52, 2018.
Article in English | MEDLINE | ID: mdl-30410547

ABSTRACT

BACKGROUND: Pulmonary inflammation and endothelial barrier permeability increase in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by pro-inflammatory cytokines and matrix metalloproteinases (MMPs). However, the relationship between pro-inflammatory cytokines and MMPs in ALI/ARDS remains poorly understood. METHODS: A lipopolysaccharide (LPS)-induced ALI rat model was established through intratracheal instillation. The wet/dry ratios of lung tissues were measured, and bronchoalveolar lavage fluid (BALF) was collected to test protein concentrations, total cell/macrophage numbers, and pro-inflammatory cytokine levels. LPS-treated alveolar macrophages were utilized in in vitro experiments. The expression and secretion of MMPs were respectively detected using quantitative PCR, Western blotting and ELISA assays. RESULTS: The levels of IL-33 and MMP2/9 in BALF increased in all the ALI rats with severe lung injury. LPS-induced IL-33 autocrine upregulated the expression of MMP2 and MMP9 through activating STAT3. Neutralizing IL-33 in culture medium with specific antibodies suppressed the expression and secretion of MMP2 and MMP9 in LPS-treated alveolar macrophages. Consistently, eliminating IL-33 decreased the levels of MMP2 and MMP9 in BALF and alleviated lung injury in ALI rats. CONCLUSION: The IL-33/STAT3/MMP2/9 regulatory pathway is activated in alveolar macrophages during acute lung injury, which may exacerbate the pulmonary inflammation.


Subject(s)
Acute Lung Injury/metabolism , Interleukin-33/metabolism , Macrophages, Alveolar/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , STAT3 Transcription Factor/metabolism , Acute Lung Injury/pathology , Animals , Cells, Cultured , Disease Models, Animal , Gene Knockdown Techniques , Inflammation Mediators/metabolism , Lipopolysaccharides , Macrophages, Alveolar/pathology , Male , Neutralization Tests , Rats, Wistar , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Necrosis Factor-alpha/metabolism
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