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Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined. The potential microRNA targeting to NDUFA4L2 was identified and its roles on LUSC cell were detected. We found that NDUFA4L2 were overexpressed in LUSC tissues, and that NDUFA4L2 expression correlated with shorter overall survival. NDUFA4L2 was regulated by HIF-1α under hypoxia, and NDUFA4L2 decreased mitochondrial reactive oxygen species (mitoROS) production through inhibiting mitochondrial complex I activity in LUSC cells. NDUFA4L2 silencing effectively suppressed LUSC cell growth and enhanced apoptosis by inducing mitoROS accumulation. Additionally, NDUFA4L2 was a target for miR-183-5p, and LUSC patients with high miR-183-5p levels had better prognoses. MiR-183-5p significantly induced mitoROS production and suppressed LUSC survival through negatively regulating NDUFA4L2 in vitro and in vivo. Our results suggested that regulation of NDUFA4L2 by HIF-1α is an important mechanism promoting LUSC progression under hypoxia. NDUFA4L2 inhibition using enforced miR-183-5p expression might be an effective strategy for LUSC treatment.
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Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Amyloid beta-Peptides/metabolism , Medicine, Chinese Traditional , Quality of Life , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/prevention & controlABSTRACT
OBJECTIVES: Pediatric patients undergoing cardiac surgery usually experience significant surgical pain. Additionally, the effect of poor surgical analgesia creates a pain continuum that extends to the postoperative period. Transversus thoracic muscle plane block (TTMPB) is a novel plane block technique that can provide analgesia to the anterior chest wall. The analgesic role of TTMPB in pediatric cardiac surgery is still uncertain. A meta-analysis was conducted to determine the analgesic efficacy of this procedure. DESIGN AND SETTING: Systematic review and meta-analysis. PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure were searched to November 2023, and the Grading of Recommendations Assessment, Development, and Evaluation approach was followed to evaluate the certainty of evidence. PARTICIPANTS: Eligible studies enrolled pediatric patients from 2 months to 12 years old scheduled to undergo cardiac surgery, and randomized them to receive a TTMPB or no block/sham block. MEASUREMENTS AND MAIN RESULTS: Six studies that enrolled 601 pediatric patients were included. Low-certainty evidence from randomized trials showed that, compared with no block or sham block, TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative modified objective pain score at 12 hours (weighted mean difference [WMD] -2.20, 95% CI -2.73 to -1.68) and 24 hours (WMD -1.76, 95% CI -2.09 to -1.42), intraoperative opioid consumption (WMD -3.83, 95% CI -5.90 to -1.76 µg/kg), postoperative opioid consumption (WMD -2.51, 95% CI -2.84 to -2.18 µg/kg), length of intensive care unit (ICU) stay (WMD -5.56, 95% CI -8.30 to -2.83 hours), and extubation time (WMD -2.13, 95% CI -4.21 to -0.05 hours). Retrospective studies provided very low certainty that the results were consistent with the randomized trials. CONCLUSION: Very low- to low-certainty evidence showed that TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative pain, opioid consumption, ICU length of stay, and extubation time.
Subject(s)
Cardiac Surgical Procedures , Nerve Block , Observational Studies as Topic , Pain, Postoperative , Randomized Controlled Trials as Topic , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/adverse effects , Nerve Block/methods , Randomized Controlled Trials as Topic/methods , Observational Studies as Topic/methods , ChildABSTRACT
Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.
Subject(s)
Gastrointestinal Diseases , Integrative Medicine , Humans , Medicine, Chinese Traditional , Gastrointestinal Diseases/prevention & control , Evidence-Based MedicineABSTRACT
Background: Functional parathyroid cysts (FPCs) are rare and difficult to diagnose with noninvasive methods. The aim of this study was to evaluate the diagnostic value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computerized tomography (SPECT/CT) parathyroid imaging in the diagnosis of FPCs and to account for its performance. Methods: The data from 10 patients with suspected parathyroid cysts (PCs) who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2012 and 2022 were retrospectively evaluated. The diagnostic value of 99mTc-MIBI SPECT/CT parathyroid imaging for FPCs was analyzed. Results: Surgical resection was performed in six cases and parathyroid puncture was performed in four cases. The sensitivity of 99mTc-MIBI SPECT/CT for FPCs was 100.0% (3/3), with a specificity of 100.0% (7/7) and an accuracy of 100.0% (10/10). The postoperative pathological findings in three cases of FPCs were parathyroid adenoma, parathyroid adenoma with hemorrhage, and parathyroid adenoma with cystic degeneration, respectively. The diagnostic accuracy of ultrasound and CT for PCs was only 22.22% (2/9) and 25.0% (1/4), respectively, and neither modality could indicate whether the cysts were functional or not. Conclusions: 99mTc-MIBI parathyroid SPECT/CT imaging has a high value in the diagnosis of FPCs in patients with suspected PCs, and an intense ring-shaped accumulation of radioactivity in the cyst wall on 99mTc-MIBI imaging suggests that the patient may have FPCs.
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Background: Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic values of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) of parathyroid glands by analyzing the relationship between lesion weight and false-negative (FN) results, as well as to explain the possible reason. Methods: The data from 314 patients with suspected HPT who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2011 and 2022 were retrospectively evaluated. The sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of parathyroid 99mTc-MIBI SPECT/CT were calculated, and the false-positive (FP) and FN findings were analyzed. Results: Accurate localization by 99mTc-MIBI SPECT/CT was significantly associated with the parathyroid hormone (PTH) level. The 99mTc-MIBI SPECT/CT for diagnosis/lesion location reached a sensitivity of 84.6%/56.8%, a PPV of 97.3%/98.4%, an NPV of only 23.7%/4.18%, and an accuracy of 83.4%/57.1%, respectively. The largest diameter, shortest diameter, and lesion volume were lower in the FN group than in the TP group. A total of 7 FP cases were found, including 2 cases of thyroid nodules, 4 cases of thyroid tissue, and 1 case of hibernoma. A total of 45 FN patients, including 321 FN lesions, were confirmed, of which parathyroid hyperplasia accounted for 97.8%. Lesion weights greater than 20 µg were able to be detected, but lightweight lesions less than 100 mg were the principal source of FN results, accounting for approximately 39.3%. With lesion weights 0-100, 101-300, 301-1,000, and >1,000 mg, the FN rate was 70.8% (126/178), 51.8% (103/199), 34.6% (81/234), and 8.33% (11/132), respectively. Conclusions: 99mTc-MIBI SPECT/CT parathyroid imaging provides good sensitivity and high specificity in HPT location. Correct localization by 99mTc-MIBI SPECT/CT correlates positively with lesion weight and PTH levels. The smaller the lesion, the higher the FN rate in 99mTc-MIBI SPECT/CT parathyroid imaging, and lesions weighing less than 100 mg are the main source of FN results in 99mTc-MIBI SPECT/CT parathyroid imaging.
ABSTRACT
Important roles in the initiation and maintenance of postoperative pain are played by the functional control of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors in the rat dorsal horn (DH). However, the mechanisms underpinning the cross-talk between spinal KA and AMPA receptors in postoperative pain are poorly understood. We hypothesized that after the rat's plantar incision, the synaptic incorporation of AMPA receptor GluR1 subunits in the DH ipsilateral to the incision would increase due to the interaction between GluK2 and neuropilin tolloid-like 2 (NETO2). Our findings showed that incision stimuli caused severe pain responses, as measured by cumulative pain scores. GluK2-NETO2 but not GluK2-NETO1interaction was upregulated in ipsilateral dorsal horn neurons (DHNs) at 6 h post-incision. At 6 h post-incision, NETO2 small interfering ribonucleic acid (siRNA) intrathecal pretreatment increased mechanical withdrawal thresholds to von Freys and decreased ipsilateral paw cumulative pain scores. Further, PKCγactivation and synaptic abundance of GluK2 and GluR1 subunits in the ipsilateral DH were decreased by intrathecal pretreatment with NETO2 siRNA at 6 h post-incision. In conclusion, our findings imply that GluK2-NETO2 interaction could trigger PKCγactivation and the synaptic incorporation of AMPA receptor GluR1 subunits in rat DHs, which in turn led to the enhanced pain hypersensitivity after surgery. It sheds light on the interplay between KA and AMPA receptors in DHNs, which is thought to contribute to postoperative pain.
Subject(s)
Receptors, AMPA , Spinal Cord Dorsal Horn , Animals , Rats , Pain, Postoperative/metabolism , Posterior Horn Cells/metabolism , Receptors, AMPA/metabolism , RNA, Small Interfering/metabolism , Spinal Cord Dorsal Horn/metabolism , GluK2 Kainate ReceptorABSTRACT
Electrocatalytic CO2 reduction via renewable electricity provides a sustainable way to produce valued chemicals, while it suffers from low activity and selectivity. Herein, we constructed a novel catalyst with unique Ti3 C2 Tx MXene-regulated Ag-ZnO interfaces, undercoordinated surface sites, as well as mesoporous nanostructures. The designed Ag-ZnO/Ti3 C2 Tx catalyst achieves an outstanding CO2 conversion performance of a nearly 100% CO Faraday efficiency with high partial current density of 22.59â mA cm-2 at -0.87â V versus reversible hydrogen electrode. The electronic donation of Ag and up-shifted d-band center relative to Fermi level within MXene-regulated Ag-ZnO interfaces contributes the high selectivity of CO. The CO2 conversion is highly correlated with the dominated linear-bonded CO intermediate confirmed by in situ infrared spectroscopy. This work enlightens the rational design of unique metal-oxide interfaces with the regulation of MXene for high-performance electrocatalysis beyond CO2 reduction.
Subject(s)
Acupuncture Therapy , Antiemetics , Laparoscopy , Humans , Vomiting/etiology , Vomiting/therapy , Nausea/etiology , Nausea/therapyABSTRACT
STUDY OBJECTIVE: The role of transversus thoracic muscle plane blocks (TTMPBs) during cardiac surgery is controversial. We conducted a systematic review to establish the effectiveness of this procedure. DESIGN: Systematic review. We searched PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure to June 2022, and followed the GRADE approach to evaluate the certainty of evidence. STUDY ELIGIBILITY CRITERIA: Eligible studies enrolled adult patients scheduled to undergo cardiac surgery and randomized them to receive a TTMPB or no block/sham block. MAIN RESULTS: Nine trials that enrolled 454 participants were included. Compared to no block/sham block, moderate certainty evidence found that TTMPB probably reduces postoperative pain at rest at 12 h [weighted mean difference (WMD) -1.51 cm on a 10 cm visual analogue scale for pain, 95% CI -2.02 to -1.00; risk difference (RD) for achieving mild pain or less (≤3 cm), 41%, 95% CI 17-65) and 24 h (WMD -1.07 cm, 95% CI -1.83 to -0.32; RD 26%, 95% CI 9-37). Moderate certainty evidence also supported that TTMPB probably reduces pain during movement at 12 h (WMD -3.42 cm, 95% CI -4.47 to -2.37; RD 46%, 95% CI 12-80) and at 24 h (WMD -1.73 cm, 95% CI -3.24 to -0.21; RD 32%, 95% CI 5-59), intraoperative opioid use [WMD -28 milligram morphine equivalent (MME), 95% CI -42 to -15], postoperative opioid consumption (WMD -17 MME, 95% CI -29 to -5), postoperative nausea and vomiting (absolute risk difference 255 less per 1000 persons, 95% CI 140-314), and intensive care unit (ICU) length of stay (WMD -13 h, 95% CI -21 to -6). CONCLUSION: Moderate certainty evidence showed TTMPB during cardiac surgery probably reduces postoperative pain at rest and with movement, opioid consumption, ICU length of stay, and the incidence of nausea and vomiting.
Subject(s)
Analgesics, Opioid , Cardiac Surgical Procedures , Adult , Humans , Analgesics, Opioid/therapeutic use , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Nausea and Vomiting , Cardiac Surgical Procedures/adverse effects , MusclesABSTRACT
OBJECTIVE: To observe the effects of transcutaneous electrical acupoint stimulation (TEAS) at different times on the stress response during anesthesia and operation in the patients undergoing open posterior lumbar surgery. METHODS: A total of 94 patients undergoing open posterior lumbar surgery were randomly assigned to preoperative TEAS group(32 cases), intraoperative TEAS group(31 cases) and sham-TEAS group(31 cases). The same anesthetic method was used in the patients of 3 groups. Four electrodes were attached to the bilateral Hegu (LI4) and Neiguan (PC6) and connected to the electronic acupuncture instrument when patients entered the operation room. In the preoperative TEAS group, the patients received TEAS (10 to 20 mA) for 30 min before the anesthetic induction. TEAS (15 mA) was provided immediately when the operation starts till the end of ope-ration for the patients of the intraoperative TEAS group. In the sham-TEAS group, the electronic acupuncture instrument was switched on during the whole procedure of operation, but no electric current was output. Separately, at the moment of entering the operation room (T0), before endotracheal intubation (T1), at the time of endotracheal intubation (T2), 10 min after skin resection (T3), at the end of surgery (T4), recovery from anesthesia (T5) and at the time of extubation (T6), the heart rate (HR) and mean arterial pressure (MAP) were recorded. Using ELISA, the concentrations of epinephrine (E), norepinephrine (NE), dopamine (DA), cortisol (Cor) in serum were assayed at T0, T3, and T4; and blood glucose was tested with blood sugar paper at the same time points. RESULTS: Compared with T0 of the same group, HR was increased at T2 and decreased at T3 of the patients in the sham-TEAS group and the intraoperative TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, HR was decreased at T2 and increased at T3 of the patients in the preoperative TEAS group (P<0.05), and it was decreased at T6 of patients in the intraoperation TEAS group (P<0.05). HR was reduced at T2 in the preoperative TEAS group when compared with the intraoperative TEAS group. Compared with T0 of the same group, MAP was elevated at T2 and reduced at T3 and T4 in the sham-TEAS group (P<0.05); it decreased at T3, T4 and T5 in the preoperative TEAS group (P<0.05); it rose at T2 and was reduced at T3, T4 and T5 in the intraoperative TEAS group (P<0.05). When compared with the sham-TEAS group at the same time points, MAP decreased at T2 in the preoperative TEAS group (P<0.05), and at T6 in the intraoperative TEAS group (P<0.05). MAP was reduced at T2 and elevated at T6 in the preoperative TEAS group in comparison with the intraoperative TEAS group (P<0.05) at the same time points. Compared with T0 of the same group, the contents of E was increased at T3 in the sham-TEAS group and the intraoperative TEAS group (P<0.05); it was increased in all of the three groups at T4 (P<0.05); the contents of NE, DA, Cor and the blood glucose were increased at T4 in the sham-TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, the contents of E, DA at T3 and T4 and Cor at T3 in serum of the preoperative TEAS group were decreased (P<0.05); and the contents of E, NE, DA and Cor at T4 in the intraoperative TEAS group were decreased (P<0.05). CONCLUSION: TEAS-assisted general anesthesia can better maintain the stability of HR and MAP during anesthesia and operation in patients undergoing open posterior lumbar surgery, and reduce surgical stress response.
Subject(s)
Transcutaneous Electric Nerve Stimulation , Humans , Transcutaneous Electric Nerve Stimulation/methods , Acupuncture Points , Blood Glucose , Anesthesia, General , Heart RateABSTRACT
INTRODUCTION: Painless gastrointestinal endoscopy is being increasingly practised in the clinical field. The management and choice of sedation are important during the endoscopy procedure to reduce patient discomfort and facilitate high disease detection rates. Ciprofol is principally an agonist of the γ-aminobutyric acid type A receptor; it comprises the active ingredient HSK3486, which is similar to the currently used intravenous anaesthetic propofol in clinical practice. A systematic review and meta-analysis comparing ciprofol and propofol will be conducted to assess their efficacy and safety during endoscopy. Before starting the study, we describe the specific protocol of this systematic review. METHODS AND ANALYSIS: This protocol was prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be searched: Embase, Cochrane Library, PubMed, Web of Science, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and a clinical trial registry. The database search strategy will adopt a combination of subject words and free words. Randomised controlled trials related to ciprofol use for sedation during gastrointestinal endoscopy will also be included. Based on the inclusion and exclusion criteria, two researchers will independently screen the articles and extracted data. Following the qualitative evaluation of each study, analysis will be conducted using Review Manager software. ETHICS AND DISSEMINATION: The protocol for this systematic review and meta-analysis involves no individual patient data; thus, ethical approval is not required. This will be the first meta-analysis to assess the sedation efficacy of ciprofol and provide evidence to clinicians for decision-making. The results will be disseminated through conference presentations and publications in peer-review journals related to this field. PROSPERO REGISTRATION NUMBER: CRD42022370047.
Subject(s)
Propofol , Humans , Systematic Reviews as Topic , Meta-Analysis as Topic , Anesthetics, Intravenous , Endoscopy, Gastrointestinal , Research DesignABSTRACT
Background: Gates' analysis method for kidney depth (KD) calculation is the only way to determine the glomerular filtration rate (GFR) of the kidney in clinical practice, which posits that the influence of KD on the GFR is more important than other factors. Computed tomography (CT) measurement of the donor KD can improve the accuracy of GFR measurement by Gates' method but will also increase the radiation exposure of kidney transplantation donors. Thus, it is particularly important to establish an accurate empirical formula for KD measurement that is more consistent with the real KD. Methods: In total, 326 potential renal transplantation donors were enrolled in this study. Among these, 167 donors were assigned to the training set to estimate the regression formula of KD measured by CT. The remaining 159 donors were included in the validation set to verify the regression formula. The KD measured by CT and its corresponding GFR was taken as the reference standard. The performances of formulas were then compared. Results: There was no significant statistical difference between the CT-measured KD and the current fitting, Li Q, and Xue JJ formulas (P>0.05). However, significant differences were observed between the KDs calculated using the Taylor, Ma G, and Uchiyama formulas and the CT-measured reference standard KD (P<0.05). Furthermore, there was no notable difference in the GFRL and GFRR corresponding to the CT-measured KD with that of the fitting, Ma G, and Xue JJ formulas (P>0.05). There were also marked differences in the GFRR corresponding to the Li Q's formula (P<0.05), and in the GFR between other estimation methods and the CT measurement (P<0.05). Conclusions: The fitting formula established in this study can play a more important role if an accurate measurement method of the body thickness at the level of the hilum on the body surface can be found.
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The astrocytes-secreted active molecule, Hevin considerably contributes in the transsynaptic bridge of neurexin1ß/neuligin1 in excitatory synapse. Previous studies have demonstrated that activity-dependent synaptic recruitment of spinal neuroligin1 and GluA1-containing AMPA receptors (AMPARs) is involved in incisional, inflammatory and neuropathic pain. Here, we hypothesized that Hevin induced postoperative pain hypersensitivity by enhancing the neurexin1ß/neuroligin1-mediated synaptic targeting of GluA1-containing AMPARs in spinal dorsal horns (DH). Our results showed that plantar incision induced significant postoperative pain behavior, which was described by the cumulative pain scores. At 1 d and 3 d post-incision, Hevin expression was considerably elevated in ipsilateral DHs, although it recovered to baseline value at 5 d following the incision. At 1 d post plantar incision, the neurexin1ß/neuroligin1 interactions significantly increased in ipsilateral DHs in rats subjected to incision when compared with those in control rats. Intrathecal pretreatments of small interference RNA targeting Hevin substantially suppressed postoperative pain hypersensitivity and reduced the neurexin1ß/neurolgin1 interaction as well as the synaptic targeting of GluA1 in ipsilateral spinal DHs. These data suggest that Hevin induced postoperative pain hypersensitivity by enhancing the neurexin1ß/neuroligin1 interaction and subsequent synaptic targeting of GluA1-containing AMPARs in ipsilateral spinal DHs. It provides new insights into the role of Hevin-mediated trans-synaptic regulation in postoperative pain hypersensitivity, which would help develop a novel therapeutic strategy.
Subject(s)
Receptors, AMPA , Spinal Cord Dorsal Horn , Animals , Calcium-Binding Proteins , Extracellular Matrix Proteins , Neural Cell Adhesion Molecules , Pain, Postoperative/metabolism , Rats , Rats, Sprague-Dawley , Receptors, AMPA/metabolism , Spinal Cord Dorsal Horn/metabolism , Up-RegulationABSTRACT
Background: Lung adenocarcinoma (LUAD), the most prevalent type of lung cancer, is often metastatic and has a poor prognosis. Recent studies have demonstrated an important role for fucosyltransferase 8 (FUT8) in carcinogenesis and cancer progression. Methods: A meta-analysis with 15 eligible datasets from Gene Expression Omnibus (GEO) was performed to explore the expression of FUT8 in LUAD. The results were further verified in The Cancer Genome Atlas (TCGA) database, followed by survival analysis using Kaplan-Meier plotter. We also validated the protein expression of FUT8 by immunohistochemistry (IHC). In vitro experiments were conducted to determine the biological effects of FUT8 in LUAD cells. Results: The meta-analysis showed the FUT8 expression in LUAD tissues was significantly higher than those in normal lung tissues [standard mean difference (SMD): 1.40; 95% confidence interval (CI): .95-1.85]. The results of TCGA database verified the expression of FUT8 increased in LUAD tissues versus normal tissues. IHC analyses indicated that the protein levels of FUT8 were up-regulated in LUAD, and elevated FUT8 expression was significantly correlated with poor prognosis in LUAD patients. Multivariable Cox regression analysis revealed that FUT8 expression was an independent prognostic factor. Besides, in vitro experiments showed that knockdown of FUT8 in LUAD cells markedly restrained cell proliferation, and stimulated cell apoptosis. Conclusion: This study indicates that increased FUT8 expression is correlated with shortened survival of LUAD patients and might favor the progression of the disease.
Subject(s)
Adenocarcinoma of Lung , Fucosyltransferases , Lung Neoplasms , Adenocarcinoma of Lung/pathology , Fucosyltransferases/genetics , Fucosyltransferases/metabolism , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lung Neoplasms/pathology , PrognosisABSTRACT
Objective: Macrophages function as key orchestrators in the pathogenesis of acute lung injury (ALI). The current study sets out to investigate the molecular mechanism of transforming growth factor-ß (TGFß1) in the regulation of M1 alveolar macrophage polarization in ALI by modulating DNA methyltransferase 1 (DNMT1), along with the microRNA (miR)-124/Pellino 1 (PELI1)/interferon regulatory factor 5 (IRF5) axis. Methods: First, ALI mouse models were established, and the proportion of M1 and M2 macrophages in mouse lung tissues was detected using flow cytometry. The targeting relationship between miR-124 and PELI1 was verified with the help of a dual luciferase gene reporter assay. Following TGFß1 knockdown, RT-qPCR and Western blot assay were performed to analyze the expression patterns of TGFß1, DNMT1, miR-124, and PELI1 and M1/M2 polarization markers in the lung tissues of ALI mice. Immunofluorescence was further employed to detect nuclear translocation of IRF5 in macrophages. Results: The polarization of M1 macrophages was found to be positively correlated with the severity of lung injury. TGFß1, DNMT1, PELI1 were highly expressed, while miR-124 was down-regulated in ALI mice, and IRF5 was primarily distributed in the nucleus. TGFß1 promoted the polarization of M1 alveolar macrophages by up-regulating DNMT1. Furthermore, DNMT1 down-regulated the expression of miR-124, which led to enhancement of M1 alveolar macrophage polarization. Meanwhile, over-expression of miR-124 inhibited the nuclear translocation of IRF5 and suppressed M1 alveolar macrophage polarization. On the other hand, over-expression of PELI1 reversed the above trends. Conclusion: Collectively, our findings indicated that TGFß1 can promote the expression of DNMT1, which down-regulates miR-124 to activate PELI1 and nuclear translocation of IRF5, thereby aggravating ALI in mice.