Dexmedetomidine improves lung injury after one-lung ventilation in esophageal cancer patients by inhibiting inflammatory response and oxidative stress.

Aim: To explore the effect of Dexmedetomidine (DEX) on lung injury in patients undergoing One-lung ventilation (OLV). Methods: Esophageal cancer patients undergoing general anesthesia with OLV were randomly divided into the DEX group and control group, with 30 cases in each group. Mean arterial pressure (MAP), heart rate (HR), arterial partial pressure of oxygen (PO2), and arterial partial pressure of nitrogen dioxide (PCO2) were recorded at the time points after anesthesia induction and before OLV (T1), OLV 30 min (T2), OLV 60 min (T3), OLV 120 min (T4), OLV end before (T5) and before leaving the room (T6) in both groups. Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was applied to detect the levels of CC16 mRNA. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CC16 protein levels. The content of malondialdehyde (MDA) in serum was determined by thio barbituric acid (TBA) method. ELISA was used to measure the concentrations of TNF-α (tumor necrosis factor-alpha)/and IL-6 (interleukin 6). Results: DEX treatment slowed down HR at time points T1-T6 and increased PO2 and PCO2 at time points T2-T5 compared with the control group. Moreover, at time points T2-T6, DEX treatment reduced the levels of club cell secretory protein-16 (CC16) mRNA and serum CC16 protein levels. Furthermore, DEX treatment caused the reduction of MDA, TNF-α and IL-6 concentrations in serum of patients. Conclusion: During the OLV process, DEX could reduce serum CC16 protein levels, inhibit inflammatory reactions and oxidative stress, and improve oxygenation index, indicating a protective effect on lung injury during OLV.

The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction.

Acute kidney injury (AKI) is a common complication of cisplatin chemotherapy, which greatly limits its clinical effect and application. This study explored the function of solute Carrier Family 31 Member 1 (SLC31A1) in cisplatin-induced AKI and its possible mechanism. Mice and HK-2 cells were exposed to cisplatin to establish the in vivo and in vitro AKI models. Cell viability was detected by CCK-8. Mitochondrial and oxidative damage was determined by Mito-Tracker Green staining, mtROS level, ATP production, mitochondrial membrane potential, MDA content and CAT activity. AKI was evaluated by renal function and histopathological changes. Apoptosis was detected by TUNEL and caspase-3 expression. Molecule expression was measured by RT-qPCR, Western blotting, and immunohistochemistry. Molecular mechanism was studied by luciferase reporter assay and ChIP. SLC31A1 level was predominantly increased by cisplatin exposure in AKI models. Notably, copper ion (Cu+) level was enhanced by cisplatin challenge. Moreover, Cu+ supplementation intensified cisplatin-induced cell death, mitochondrial dysfunction, and oxidative stress in HK-2 cells, indicating the involvement of cuproptosis in cisplatin-induced AKI, whereas these changes were partially counteracted by SLC31A1 knockdown. E74 like ETS transcription factor 3 (ELF3) could directly bind to SLC31A1 promoter and promote its transcription. ELF3 was up-regulated and positively correlated with SLC31A1 expression upon cisplatin-induced AKI. SLC31A1 silencing restored renal function, alleviated mitochondrial dysfunction, and apoptosis in cisplatin-induced AKI mice. ELF3 transcriptionally activated SLC31A1 to trigger cuproptosis that drove cisplatin-induced AKI through mitochondrial dysfunction, indicating that SLC31A1 might be a promising therapeutic target to mitigate AKI during cisplatin chemotherapy.

Paravertebral block's effect on analgesia and inflammation in advanced gastric cancer patients undergoing transarterial chemoembolization and microwave ablation.

BACKGROUND: Transarterial chemoembolization (TACE) combined with microwave ablation (MWA) is an effective treatment strategy for patients with advanced gastric cancer and liver metastasis. However, it may cause severe postoperative pain and inflammatory responses. The paravertebral block (PVB) is a regional anesthetic technique that provides analgesia to the thoracic and abdominal regions. AIM: To evaluate the effect of PVB on postoperative analgesia and inflammatory response in patients undergoing TACE combined with MWA for advanced gastric cancer and liver metastasis. METHODS: Sixty patients were randomly divided into PVB and control groups. The PVB group received ultrasound-guided PVB with 0.375% ropivacaine preoperatively, whereas the control group received intravenous analgesia with sufentanil. The primary outcome was the visual analog scale (VAS) score for pain at 6 h, 12 h, 24 h, and 48 h after the procedure. Secondary outcomes were the dose of sufentanil used, incidence of adverse events, and levels of inflammatory markers (white blood cell count, neutrophil percentage, C-reactive protein, and procalcitonin) before and after the procedure. RESULTS: The PVB group had significantly lower VAS scores at 6 h, 12 h, 24 h, and 48 h after the procedure compared with the control group (P < 0.05). The PVB group also had a significantly lower consumption of sufentanil and a lower incidence of nausea, vomiting, and respiratory depression than did the control group (P < 0.05). Compared with the control group, the PVB group had significantly lower levels of inflammatory markers 24 h and 48 h after the procedure (P < 0.05). CONCLUSION: PVB can effectively reduce postoperative pain and inflammatory responses and improve postoperative comfort and recovery in patients with advanced gastric cancer and liver metastasis treated with TACE combined with MWA.

Ropivacaine suppresses the progression of renal cell carcinoma through regulating the lncRNA RMRP/EZH2/CCDC65 axis.

BACKGROUND: Renal cell carcinoma (RCC) is a common malignancy. Local anesthetics were displayed powerful effects against various cancers. This study aims to probe the functions and molecular mechanism of ropivacaine in RCC. METHODS: Different concentrations of ropivacaine were performed to administrate RCC cells including 786-O and Caki-1 cells. Cell viability and cell apoptosis were examined using CCK-8 and flow cytometry, respectively. Cell migration and invasion were determined by transwell assay. RMRP and CCDC65 expression was firstly predicted using TCGA dataset and further validated in RCC cells using qRT-PCR and western blot. The interactions among RMRP, EZH2 and CCDC65 were verified by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays. RESULTS: Ropivacaine effectively suppressed RCC cell viability, migration and invasion and enhanced cell apoptosis rate. Aberrantly elevated RMRP expression in RCC tissues was predicted by TCGA database. Interestingly, overexpressed RMRP observed in RCC cells could be also blocked upon the administration of ropivacaine. Likewise, RMRP knockdown further strengthened ropivacaine-mediated tumor suppressive effects on RCC cells. In terms of mechanism, RMRP directly interacted with EZH2, thereby modulating the histone methylation of CCDC65 to silence its expression. Moreover, ropivacaine inhibited tumor growth in mice bearing RCC tumor through regulating RMRP/EZH2/CCDC65 axis. CONCLUSION: In sum up, our work revealed that ropivacaine suppressed capacities of RCC cell viability, migration and invasion through modulating the RMRP/EZH2/CCDC65 axis, which laid the experimental foundation of ropivacaine for clinical application in the future.

Long non-coding RNA MEG3 alleviates postoperative cognitive dysfunction by suppressing inflammatory response and oxidative stress via has-miR-106a-5p/SIRT3.

Postoperative cognitive dysfunction (POCD), a neurological complication after surgery, is common among the elderly in particular. Maternal expression gene 3 (MEG3) is a novel long non-coding RNA (lncRNA) that contributes to glial cell activation and inflammation. We aim to further explore its role in POCD. Mice were induced with sevoflurane anesthesia and underwent orthopedic surgery to establish a POCD model. BV-2 microglia activation was induced by lipopolysaccharide. The overexpressed lentiviral plasmid lv-MEG3 and its control were injected into mice. pcDNA3.1-MEG3, has-miR-106a-5p mimic, and its negative control were transfected into BV-2 cells. The expressions of has-miR-106a-5p MEG3 and Sirtuin 3 (SIRT3) in rat hippocampus and BV-2 cells were quantitatively detected. Levels of SIRT3, TNF-α, and IL-1ß were detected by western blot, levels of TNF-α and IL-1ß by ELISA, and expression of GSH-Px, SOD, and MDA by kits. The targeting relationship between MEG3 and has-miR-106a-5p was confirmed using bioinformatics and dual-luciferase reporter assay. LncRNA MEG3 was down-regulated in POCD mice, whereas has-miR-106a-5 levels were up-regulated. Overexpression of MEG3 could attenuate cognitive dysfunction and inflammatory response in POCD mice, inhibit lipopolysaccharide-induced inflammatory response and oxidative stress in BV-2 cells, and promote has-miR-106a through competitive binding with has-miR-106a-5-5 expression of target gene SIRT3. Overexpression of has-miR-106a-5p had a reverse effect on overexpression of MEG3 functioning on lipopolysaccharide-induced BV-2 cells. LncRNA MEG3 could inhibit the inflammatory response and oxidative stress via has-miR-106a-5p/SIRT3, thereby reducing POCD, which might be a potential biological target for the diagnosis and treatment of clinical POCD.

Effect of neurotropin on Alzheimer's disease-like changes and cognitive function in rats with chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a main mechanism of cerebrovascular disease and is associated with various cerebrovascular and neurodegenerative diseases, including Alzheimer's disease. However, treatment of CCH in clinical practice is not ideal, but neurotropin (NTP) has been shown to have a neuroprotective effect. Therefore, this study examined the effect and possible mechanism of NTP in nerve injury caused by CCH. A rat CCH model was established by bilateral common carotid artery occlusion (2VO), and rats were treated with intragastric administration of NTP (200 nu/kg/day) for 28 consecutive days. After treatment, rats were subjected to the Morris water maze and novel object recognition test. Subsequently, an ELISA was applied to detect amyloid-ß (Aß) 1-40 and Aß1-42 levels in rat hippocampal tissues, quantitative reverse transcription PCR assays were used to detect the mRNA expression levels of brain-derived neurotrophic factor (BDNF) and Trk B, and Western blots were used to detect the protein expression levels of BACE1, tau, p-tau, and protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK3ß) pathway-related proteins. The rat model of CCH was successfully established by 2VO. Behavioral tests indicated that the cognitive ability of 2VO rats was severely impaired. NTP treatment greatly ameliorated the cognitive disability, reduced Aß1-40 and Aß1-42 levels and tau phosphorylation, and upregulated BACE1, Trk B, and BDNF expression in the hippocampus of 2VO rats. Finally, we found that NTP markedly activated Akt/GSK3ß pathway activity. NTP can ameliorate cognitive disability in CCH rats possibly by reducing Aß accumulation and tau phosphorylation in the hippocampus. These effects of NTP may be related to the Akt/GSK3ß pathway activation. NTP may be a promising new drug candidate for CCH patients.

Dexmedetomidine reduces the apoptosis of rat hippocampal neurons via mediating ERK1/2 signal pathway by targeting miR-155.

Rat hippocampal neurons were isolated and divided into Normal, oxygen glucose deprivation/reoxygenation (OGD/R), OGD/R + DEX, OGD/R + NC mimic, OGD/R + miR-155 mimic and OGD/R + DEX + miR-155 mimic groups. In OGD/R group, LDH, ROS and MDA levels and apoptosis rate was increased, with up-regulations of miR-155, Cyt c and Bax/Bcl-2 ratio, but decreases of SOD, GSH-Px and MMP levels, as well as down-regulations of p-ERK1/2/ERK1/2. As compared to the OGD/R group, parameters above in the OGD/R + DEX group were ameliorated evidently, while OGD/R + miR-155 mimic group manifested the opposite changes. Besides, miR-155 mimic could abolish the protective effect of DEX on the hippocampal neurons under OGD/R. DEX, via down-regulating the expression of miR-155, could activate the ERK1/2 pathway, thereby mitigating the apoptosis and oxidative stress injury and increasing the MMP, thereby protecting hippocampal cells from OGD/R injury.

Dexmedetomidine protects rats from postoperative cognitive dysfunction via regulating the GABAB R-mediated cAMP-PKA-CREB signaling pathway.

This work attempts to discuss whether dexmedetomidine (Dex) can protect rats from postoperative cognitive dysfunction (POCD) through regulating the γ-aminobutyric acid-B receptor (GABAB R)-mediated cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) - cAMP-response element binding (cAMP-PKA-CREB) signaling pathway. Sprague-Dawley rats were divided into a non-surgical group (Control), a surgical group (Model), a surgical group treated with Dex (Model + Dex), a surgical group treated with GABAB R antagonist (Model + CGP 35348) and a surgical group treated with Dex and GABAB R agonist (Model + Dex + Baclofen). Cognitive and memory functions were evaluated by Y-maze test and open-field test. The neuronal morphology of the hippocampus was observed by hematoxylin and eosin staining and neuronal apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling method. Inflammatory factors and cAMP levels were detected by enzyme-linked immunosorbent assay while expressions of GABAB R and PKA-CREB pathway-related molecules by Western blot. Compared with control rats, the model rats exhibited reduced alternation rates with a prolonged time spent in the central zone; meanwhile, levels of tumor necrosis factor-α and interleukin-1ß and the apoptotic index, as well as GABAB R1 and GABAB R2 expressions were increased in the model rats, but the cAMP-PKA-CREB pathway was inhibited (all P < 0.05). When treated with either Dex or CGP 35348, the surgical rats displayed an opposite tendency concerning the above factors as compared to the model rats (all P < 0.05). Furthermore, Baclofen, the agonist of GABAB R, could reverse the protective effect of Dex against POCD in rats. Dex protects rats from POCD possibly via suppressing GABAB R to up-regulate the cAMP-PKA-CREB signaling pathway, thereby alleviating the hippocampal inflammation caused by surgical trauma.