Effect of Mild Therapeutic Hypothermia Combined with Stereotactic Aspiration on Patients with Severe Cerebral Hemorrhage.

This study aimed to investigate the effects of mild therapeutic hypothermia combined with stereotactic aspiration of spontaneous intracerebral hematoma on neurological function, inflammatory markers, cerebral hematoma, and cerebral edema in patients with severe cerebral hemorrhage. The clinical data of 86 patients with severe cerebral hemorrhage treated at our hospital between March 2020 and January 2022 were retrospectively analyzed. The patients were grouped according to their treatment plans: the control group consisted of 40 patients who underwent stereotactic aspiration of the spontaneous intracerebral hematoma, whereas the study group consisted of 46 patients who received adjuvant mild therapeutic hypothermia in addition to the aforementioned treatment. Clinical efficacy, neurological function (NIHSS score), daily living ability (BI score), cerebral hematoma, cerebral edema, cerebral hemodynamics (PI, RI, Vm, Vd), inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP), oxidative stress indicators (SOD, MDA, 8-iso-PGF2α), serum-related factors (MMP-9, ICAM-1, ET-1, NO), and prognosis were compared between the groups. The total efficacy rate in the study group (95.65%) was significantly higher than that in the control group (77.50%) (P < 0.05). Post-treatment NIHSS scores, intracranial hematoma volume, perihematoma edema volume, cerebral edema volume, RI, serum IL-6, IL-8, TNF-α, hs-CRP, MDA, and 8-iso-PGF2α levels were significantly lower in both groups, with the study group showing even greater reductions. The BI score and PI, Vm, Vd, SOD, and NO levels were significantly higher in the study group (P < 0.05). At the 6-month follow-up, the prognosis of patients in the intervention group was significantly better than that of patients in the control group (P < 0.05). The combination of mild therapeutic hypothermia with stereotactic aspiration of a spontaneous intracerebral hematoma has demonstrated efficacy in the treatment of severe cerebral hemorrhage. This approach effectively reduces cerebral hematoma and edema, improves daily living ability, alleviates neurological deficits, regulates cerebral hemodynamics, suppresses inflammatory responses and oxidative stress, modulates serum-related factor levels, and enhances patient prognosis.

Gentiopicroside alleviates acute myocardial infarction injury in rats by disrupting Nrf2/NLRP3 signaling.

The objective of the present investigation was to assess the protective impact of gentiopicroside (GPS) on acute myocardial infarction (AMI) through the modulation of NF-E2-related factor 2 (Nrf2)/nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) signaling. H9c2 cells were subjected to varying concentrations of GPS, and subsequently, the cells and Sprague-Dawley (SD) rats were segregated into control, model, GPS, t-BHQ (an Nrf2 activator), and GPS + ML385 (an Nrf2 inhibitor) groups. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were analyzed. Reactive oxygen species (ROS) and cell apoptosis were assessed, while Nrf2 and the expression of the NLRP3 inflammatory body signal pathway were evaluated using western blot and immunofluorescence techniques. The infarct area and pathological changes were also examined. Treatment with varying doses of GPS resulted in increased viability of H9c2 cells. Notably, the model group exhibited significantly elevated levels of cell apoptosis, MDA, and ROS compared to the control group, while SOD and Nrf2 levels were significantly reduced. Furthermore, the expression of NLRP3, cleaved caspase-1, interleukin (IL)-1ß, and IL-18 were found to be augmented. Following the implementation of GPS in cells and animals, there was a notable reduction in MDA and ROS levels, a decrease in the rate of cellular apoptosis, and a mitigation of inflammation scores. In addition, there was an increase in the expression of SOD and Nrf2. However, the protective effects of GPS were negated when co-administered with ML385. GPS exhibits therapeutic properties in AMI rats by activating Nrf2 expression, thereby reducing the NLRP3 inflammatory body and alleviating the inflammatory response and oxidative stress of myocardial cells. GPS may hold promise as a potential drug for the treatment of AMI.

In vivo and in vitro impact of atorvastatin against myocardial ischaemia-reperfusion injury by upregulation of silent information regulator l and attenuation of endoplasmic reticulum stress-induced apoptosis.

We aimed to investigate the effects and mechanism of Atorvastatin on Myocardial Ischaemia-Reperfusion Injury in vitro and in vivo. The effects of Atorvastatin on Silent information regulator l (SIRT1) and endoplasmic reticulum (ER) stress were investigated in Myocardial ischaemia-reperfusion (MI/R) injury rat model and hypoxia/reoxygenation (H/R)-treated H9c2 cells. Pathological changes, inflammatory and heart injury markers, cell apoptosis and cell death, SIRT1 and cleaved Caspase-12 expressions, and ER stress relative proteins were measured through HE, enzyme-linked immunosorbent assay, quantitative TUNEL and flow cytometry, immunofluorescence and Western blotting with the assistance of the SIRT1 specific inhibitor EX527 and ER stress pathway blocker treatment. The results of our study demonstrated that atorvastatin treatment attenuated MI/R and H/R mediated inflammatory and heart injury markers, cell apoptosis and cell death, SIRT1 and cleaved Caspase-12 expressions, and ER stress relative protein levels. Finally, we found that atorvastatin reversed SIRT1 expression and blockade the ER stress pathway and increase the cardiomyocytes survival rate in the presence of MI/R and H/R. Our findings provided a new rationale for subsequent academic and clinical research on MI/R injury.

Nrf2 overexpression protects against paraquat-induced A549 cell injury primarily by upregulating P-glycoprotein and reducing intracellular paraquat accumulation.

Paraquat (PQ) intoxication causes thousands of mortalities every year, worldwide. Its pulmonary-targeted accumulation and the acute lung injury it subsequently causes, remain a challenge for detoxification treatment. A previous study has demonstrated that the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) prevents PQ toxicity in cell line and murine models. As Nrf2 target genes include a group of membrane transporters, the current study assessed the protective mechanism exerted by Nrf2 against PQ toxicity and intracellular PQ accumulation via its effects on P-glycoprotein (P-gp), a downstream transporter of Nrf2. Adenovirus vectors containing the Nrf2 gene were transfected into A549 cells. Cell proliferation was assessed by Cell Counting Kit-8. The levels of LDH, MDA, SOD, TNF-α, IL-6 levels were detected using their respective ELISA kits. In addition, the levels of Nrf2 and P-gp protein expression were detected by western blot analysis. The concentration of PQ was measured by HPLC. The results revealed that overexpressed Nrf2 significantly increased P-gp protein levels, decreased the intracellular accumulation of PQ and attenuated PQ-induced toxicity. However, the protective effects of Nrf2 overexpression on PQ-challenged A549 cells were abrogated following cyclosporine A treatment, a competitive inhibitor of P-gp, which also increased intracellular PQ levels. These data indicated that Nrf2 gene overexpression prevented PQ toxicity in A549 cells, potentially via the upregulation of P-gp activity and the inhibition of intracellular PQ accumulation. Thus, Nrf2 and P-gp may serve as potential therapeutic targets for the treatment of PQ-induced injury.

[Curcumin reduces paraquat-induced oxidative injury in A549 cells by activation of the Nrf2-ARE pathway].

OBJECTIVE: To investigate the protective effect of curcumin (CU) on type II alveolar epithelial cells (A549 cells) during paraquat (PQ)-induced oxidative damage and its underlying mechanism. METHODS: Routinely cultured A549 cells were divided into blank control group, CU control group, PQ group, and PQ+Cu group to receive respective treatments for 24 h. Cell viability was determined by MTT assay. The NFE2L2 expression in A549 cells was measured by RT-PCR and Western blot. The activities of the heme oxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase 1 (NQO-1) in cells and the superoxide dismutase (SOD) and catalase (CAT) in supernatant, as well as malondialdehyde (MDA) content, were measured by enzyme-linked immunosorbent assay. After siRNA depletion of Nrf2, the protective effect of CU on A549 cells during PQ-induced oxidative damage was evaluated. RESULTS: PQ, even at a dose of 0.1 mmol/L, could significantly suppress the viability of A549 cells in a dose-dependent manner. CU showed no significant inhibitory effect on the viability of A549 cells when given at a dose below 160 ümol/L. Compared with the blank control group, the PQ group had significantly decreased SOD activity and significantly increased CAT activity and MDA content after 24-h exposure to 800 ümol/L PQ (P < 0.05 or P < 0.01). Thanks to pretreatment with 80 ümol/L CU, the PQ+CU group had significantly increased SOD and CAT activities and significantly decreased MDA content compared with the PQ group (P < 0.01). Compared with the blank control group, the PQ group had significantly increased expression of NFE2L2 and its downstream factors HO-1 and NQO-1 (P < 0.01), while the PQ+CU group had significantly higher expression of NFE2L2, HO-1,and NQO-1 than the PQ group (P < 0.01).Compared with the PQ+CU group, the CU+PQ+NFE2L2siRNA group had significantly decreased SOD and CAT activities and significantly increased MDA content (P < 0.01). CONCLUSION: Low-dose CU significantly reduces the PQ-induced oxidative damage in A549 cells in vitro by activation of the Nrf2-ARE pathway.

[Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

OBJECTIVE: To investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism. METHODS: Male ICR mice were randomly allocated to negative control group (n = 30), thalidomide control group (n = 30), paraquat poisoning group (n = 30), 50 mg/kg thalidomide treatment group (n = 30), 100 mg/kg thalidomide treatment group (n = 30), and 150 mg/kg thalidomide treatment group (n = 30). The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50, 100, or 150 mg/kg) 1 h later. All mice were anesthetized and sacrificed at 1, 3, or 7 d after paraquat poisoning, and their lung tissue was collected. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-kgr;B p65 was measured by Western blot. The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated. RESULTS: Compared with the negative control group, the paraquat poisoning group had significantly increased levels of TNF-α, IL-1ß, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratio of the lung (P < 0.05). Compared with the paraquat poisoning group, the thalidomide treatment groups had significantly decreased levels of TNF-α, IL-1ß, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratios of the lung (P < 0.05), and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α, IL-1ß, IL-6, NF-κB mRNA, and nuclear NF-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups. CONCLUSION: Thalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1ß, and IL-6.