Ang-1 promotes tumorigenesis and mediates the anti-cancer effects of Artesunate on Choroidal melanoma via the regulation of Akt/mTOR signaling pathway.

The impact of Ang-1 on tumors remains a subject of contention, with its mechanism of action exhibiting complexity in the progression of diverse tumor types. Ang-1 has been shown to promote the progression of glioma, glioma, esophageal and human cervical cancer, whereas it exerts inhibitory effects on the growth of breast and colon cancer. However, the specific function of Ang-1 in CM has not been clarified. This research aims to explore the function of Ang-1 on CM and the underlying mechanism. WB and qPCR were utilized to measure the expression levels of different factors in CM cells. Clonogenic, CCK-8 and Transwell migration assay were used to probe CM cells' proliferation and migration ability. Xenograft tumor model was used to testify the effect of Ang-1 and Artesunate (ART) on the growth of CM in vivo. We found Ang-1 promoted CM proliferation and migration, while it was inhibited by ART in vitro. Moreover, both ART treatment and Ang-1 knockdown had the effect of suppressing tumor growth in CM xenograft model. Mechanically, Ang-1 activated Akt/mTOR pathway and induced epithelial-mesenchymal transition (EMT) in CM cells. Furthermore, ART regulated Akt/mTOR pathway by decreasing the expression of Ang-1 in CM cells. Ang-1 promotes tumorigenesis of CM by regulating Akt/mTOR pathway, which can be inhibited by ART.

Global research trends and hotspots of oxidative stress in diabetic retinopathy (2000-2024).

Introduction: Oxidative stress has been identified as a major contributor to the pathogenesis of DR, and many diagnostic and therapeutic strategies have been developed to target oxidative stress. Our aim was to understand the contribution of the country of origin of the publication, the institution, the authors, and the collaborative relationship between them. Methods: We performed a bibliometric analysis to summarize and explore the research hotspots and trends of oxidative stress in the DR. Results: We observe an upward trend in the number of posts on related topics from year to year. Expanding on this, Queens University Belfast is the most influential research institution. Current research hotspots and trends focus on the mechanism of autophagy and NLRP3 inflammasome's role in oxidative stress in DR. Discussion: We conducted a multi-dimensional analysis of the research status of oxidative stress in diabetic retinopathy through bibliometric analysis, and proposed possible future research trends and hotspots.

Integrating network pharmacology, molecular docking and experimental verification to reveal the mechanism of artesunate in inhibiting choroidal melanoma.

Background: Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation. Methods: Potential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice. Results: Research has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM. Conclusion: This study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

Analyzing noncovalent interactions between notoginseng saponins and lysozyme by deposition scanning intensity fading MALDI-TOF mass spectrometry.

Analysis of noncovalent interactions between natural products and proteins is important for rapid screening of active ingredients and understanding their pharmacological activities. In this work, the intensity fading MALDI-TOF mass spectrometry (IF-MALDI-MS) method with improved reproducibility was implemented to investigate the binding interactions between saponins from Panax notoginseng and lysozyme. The benchmark IF-MALDI-MS experiment was established using N,N',N″-triacetylchitotriose-lysozyme as a model system. The reproducibility of ion intensities in IF-MALDI-MS was improved by scanning the whole sample deposition with a focused laser beam. The relative standard deviation (RSD) of deposition scanning IF-MALDI-MS is 5.7%. Similar decay trends of the relative intensities of notoginseng saponins against increasing amounts of lysozyme were observed for all six notoginseng saponins. The half-maximal fading concentration (FC50) was calculated to quantitatively characterize the binding affinity of each ligand based on the decay curve. According to the FC50 values obtained, the binding affinities of the six notoginseng saponins were evaluated in the following order: notoginsenoside S > notoginsenoside Fc > ginsenoside Rb1 > ginsenoside Rd > notoginsenoside Ft1 > ginsenoside Rg1. The binding order was in accordance with molecular docking studies, which showed hydrogen bonding might play a key role in stabilizing the binding interaction. Our results demonstrated that deposition scanning IF-MALDI-MS can provide valuable information on the noncovalent interactions between ligands and proteins.

TREM2 Alleviates Subarachnoid Hemorrhage-Induced Brain Injury through Attenuating Neuroinflammation and Programmed Cell Death in Vivo and in Vitro.

BACKGROUND: Apoptosis and pyroptosis are two types of programmed cell death related to the neuroinflammatory reaction after subarachnoid hemorrhage (SAH). Research indicates that triggering receptor expressed on myeloid cells 2 (TREM2) can regulate the SAH-induced inflammatory response. However, whether TREM2 regulates programmed cell death (apoptosis and pyroptosis) remains to be clarified. The purpose of the present study was to investigate the effects of TREM2 on cell death in SAH. METHODS: SAH was induced in adult male C57BL/6J mice by endovascular perforation. An in-vitro cellular model of SAH was established by treating cocultured BV2 microglia and HT22 neuronal cells with oxyhemoglobin. TREM2 overexpression or knockdown was carried out by intraventricular lentivirus injection at 7 d before SAH induction in mice or lentiviral transfection, respectively. Neurobehavioral tests as well as western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Evans blue (EB) staining, Nissl staining, and flow cytometry assays were performed to investigate the neuroprotective role of TREM2 after SAH. RESULTS: After SAH, the TREM2 mRNA and protein levels were elevated in SAH mice, exhibiting a peak at 72 h. TREM2 overexpression improved the SAH-induced neurological deficits in mice, while TREM2 knockdown worsened them. In the brains of mice with TREM2 overexpression, less neuronal death and more neuronal survival were detected at 72 h post SAH. Meanwhile, TREM2 overexpression showed an inhibitory effect on microglial activation, neutrophil infiltration, and the expression of cell death marker proteins. Consistent results were obtained in vitro. CONCLUSIONS: Our research indicates the important role of TREM2 on cell death after SAH, suggesting that targeting TREM2 might be an effective approach for treating SAH.

Early and delayed blood-brain barrier permeability predicts delayed cerebral ischemia and outcomes following aneurysmal subarachnoid hemorrhage.

OBJECTIVES: This study aimed to monitor blood-brain barrier permeability within 24 h and during the delayed cerebral ischemia (DCI) time window (DCITW) spanning 4-14 days after aneurysmal subarachnoid hemorrhage (aSAH) and to investigate its correlation with both DCI occurrence and outcomes at three months. METHODS: A total of 128 patients were stratified based on the DCI occurrence and three-month modified Rankin scale scores. Comparison of Ktrans at admission (admission Ktrans) and during DCITW (DCITW Ktrans) was conducted between DCI and non-DCI groups, as well as between groups with good and poor outcomes. Changes in Ktrans were also analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DCI and poor outcomes. RESULTS: Admission Ktrans (0.58 ± 0.18 vs 0.47 ± 0.12, p = 0.002) and DCITW Ktrans (0.54 ± 0.19 vs 0.41 ± 0.14, p < 0.001) were significantly higher in the DCI group compared with the non-DCI group. Although both were higher in the poor outcome group than the good outcome group, the difference was not statistically significant at admission (0.53 ± 0.18 vs 0.49 ± 0.14, p = 0.198). Ktrans in the non-DCI group (0.47 ± 0.12 vs 0.41 ± 0.14, p = 0.004) and good outcome group (0.49 ± 0.14 vs 0.41 ± 0.14, p < 0.001) decreased significantly from the admission to DCITW. Multivariate analysis identified DCITW Ktrans and admission Ktrans as independent predictors of poor outcomes (OR = 1.73, 95%CI: 1.24-2.43, p = 0.001) and DCI (OR = 1.75, 95%CI: 1.25-2.44, p = 0.001), respectively. CONCLUSION: Elevated Ktrans at admission is associated with the occurrence of DCI. Continuous monitoring of Ktrans from admission to DCITW can accurately identify reversible and irreversible changes and can predict outcomes at 3 months. CLINICAL RELEVANCE STATEMENT: Ktrans measured with CT perfusion is a valuable tool for predicting both delayed cerebral ischemia and three-month outcomes following aneurysmal subarachnoid hemorrhage. Monitoring changes in Ktrans from admission to time window of delayed cerebral ischemia can guide treatment and management decisions for aneurysmal subarachnoid hemorrhage patients. KEY POINTS: • Ktrans measured at admission and during the delayed cerebral ischemia time window (4-14 days) holds distinct clinical significance following aneurysmal subarachnoid hemorrhage. • Admission Ktrans serves as a predictor for delayed cerebral ischemia, while continuous assessment of Ktrans from admission to the delayed cerebral ischemia time window can predict three-month outcomes. • Monitoring Ktrans at different stages improves instrumental in enhancing decision-making and treatment planning for patients with aneurysmal subarachnoid hemorrhage.

Smoke veil prior regularized surgical field desmoking without paired in-vivo data.

Though deep learning-based surgical smoke removal methods have shown significant improvements in effectiveness and efficiency, the lack of paired smoke and smoke-free images in real surgical scenarios limits the performance of these methods. Therefore, methods that can achieve good generalization performance without paired in-vivo data are in high demand. In this work, we propose a smoke veil prior regularized two-stage smoke removal framework based on the physical model of smoke image formation. More precisely, in the first stage, we leverage a reconstruction loss, a consistency loss and a smoke veil prior-based regularization term to perform fully supervised training on a synthetic paired image dataset. Then a self-supervised training stage is deployed on the real smoke images, where only the consistency loss and the smoke veil prior-based loss are minimized. Experiments show that the proposed method outperforms the state-of-the-art ones on synthetic dataset. The average PSNR, SSIM and RMSE values are 21.99±2.34, 0.9001±0.0252 and 0.2151±0.0643, respectively. The qualitative visual inspection on real dataset further demonstrates the effectiveness of the proposed method.

Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 µmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 µg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 µg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

The relationship between childhood maltreatment and learning engagement of high school students: the role of growth mindset and beliefs about adversity.

Objective: To explore the relationship between childhood maltreatment, growth mindset, beliefs about adversity and learning engagement among high school students. Methods: Research participants were selected by random cluster sampling.652 high school students (50.2% male and 49.8% female) from five high schools were investigated using paper-pencil survey versions of Child Trauma Questionnaire, The Utrecht Work Engagement Scale-student, Growth Mindset Scale, and The Beliefs About Adversity Scale. Results: Childhood maltreatment had a significant negative effect on high school students' learning engagement. Childhood maltreatment directly predicted high school students' learning engagement and also had an indirect negative predictive effect on learning engagement via growth mindset. Conclusion: Growth mindset plays a mediating role between childhood maltreatment and learning engagement. The beliefs about adversity moderated the relationship between childhood maltreatment and growth mindset, as well as the relationship between childhood maltreatment and learning engagement. This study has empirical implications for helping high school students who have experienced childhood maltreatment to develop growth mindset and teaching students to adopt positive adversity beliefs in response to trauma during psychological interventions, thereby increasing high school students' engagement in learning.

The effect of customer satisfaction on floral product purchase behavior, evidence from Shanghai, China.

China's flower industry is developing rapidly, and the size of the retail market is increasing year by year. Studying the factors influencing residents' flower purchasing behavior and understanding their flower needs can help promote the sustainable development of the flower industry. Based on customer satisfaction theory, this paper uses 838 consumer research questionnaires from 15 districts in Shanghai to analyze the influence of customer satisfaction on residents' flower purchasing behavior by conducting a binary logit model and to investigate the moderating effect of flower purchasing purpose on the influence of satisfaction. The results show that price satisfaction and satisfaction with promotional methods have a significant negative effect on flower purchasing behavior, service satisfaction has a significant positive effect on purchasing behavior, and different customer purchase purposes lead to different intensities of the effect of satisfaction on purchasing behavior. According to the conclusion of the study, three countermeasures are proposed: to popularize the knowledge of flower culture, guide the concept of flower consumption, and promote the transformation of flower consumption to daily consumption; to conduct regular research on consumers by flower merchants to clarify consumers' needs and improve their satisfaction; to clarify consumers' purchase intention, increase the investment in the research and development and cultivation of flower products, and improve the supply level of flowers.

Enterprise 2 Stent-Assisted Embolization of Paraclinoid Aneurysms: A Single Center Preliminary Study.

Objective: Enterprise stent has been widely used for assisted embolization in wide-necked aneurysms while delayed ischemia or thromboembolic complications for its incomplete stent apposition. The purpose of this study was to summarize and analyze the clinical experience of using Enterprise 2 (EP2) stent-assisted embolization in the treatment of paraclinoid aneurysms. Methods: From January 2019 to December 2020, the clinical and imaging data of 98 patients with paraclinoid aneurysms treated with EP2 stent-assisted embolization were enrolled retrospectively. Preliminary experience and follow-up outcomes of EP2 stent-assisted embolization of paraclinoid aneurysms were assessed by using the Raymond grade and modified Rankin Scale. Results: Of the 98 aneurysms, all stents were released satisfactorily. The immediate postprocedural angiography revealed a complete occlusion of the aneurysms with 77.55% of the (76/98) patients, and the last follow-up angiograms showed complete occlusion with 83.67% of the (82/98) patients. The average aneurysm size was (4.11 ± 1.25) mm, the aneurysm diameter was (4.41 ± 1.37) mm, the vessel radius was (3.87 ± 0.32) mm, the diameter at the distal of stent was (3.23 ± 0.21) mm, and the proximal was (4.18 ± 0.23) mm. Among the 98 aneurysms, 13 cases had incomplete stent apposition, 3 cases had intraoperative knotting, and the stents were improved post adjusted; 2 cases had vasospasm and 1 case had stenosis during operation, the symptoms were improved after symptomatic treatment. The result demonstrated that stent length and inner bending radius of parent artery were the pivotal factors affecting incomplete stent apposition (P < 0.01). Conclusion: The EP2 stent for the treatment of paraclinoid aneurysms is safe and effective, however, the length of the stent and the inner bending radius of parent artery are important factors affecting incomplete stent apposition.

Safety and effectiveness of double microcatheter technique in the treatment of ruptured aneurysms of anterior cerebral circulation.

Objective: To evaluate the safety and effectiveness of the double microcatheter technique in the treatment of ruptured aneurysms of the anterior cerebral circulation. Methods: Between 2012 and 2019, 113 patients with ruptured aneurysms of the anterior cerebral circulation were treated using the double microcatheter technique. Clinical records, angiographic results, and procedure-related complications were reviewed. Clinical and angiographic follow-up was performed. Results: Complete occlusion, neck remnant, and partial occlusion were, respectively, recorded in 56.6, 38.9, and 4.4% of the total cases. For all patients, the incidence of intraoperative complications was 5.3% (6/113), and the overall rate of morbidity was 10.6% (12/113). Before discharge, three patients (2.7%) died. There was no procedure-related mortality. At discharge, favorable outcomes were observed in 79.6% (90/113) of the patients. High Hunt-Hess grades and receiving a craniotomy or external ventricular drainage were risk factors for clinical outcomes at discharge. Clinical follow-up was performed in 91 patients at a mean interval of 14.07 ± 11.68 months. At follow-up, favorable outcomes were observed in 92.3% (84/91) of the patients. Angiographic follow-up was performed in 66 patients at an average of 11.53 ± 11.13 months. The recurrence rate was 37.9%. Of these patients, 13 (19.7%) received retreatment. Conclusion: The double microcatheter technique can be performed in ruptured aneurysms with high technical success and low morbidity/mortality. However, recurrence remains a problem, and patients should be followed up regularly.

Pterostilbene Attenuates Subarachnoid Hemorrhage-Induced Brain Injury through the SIRT1-Dependent Nrf2 Signaling Pathway.

Neuroinflammatory injury, oxidative insults, and neuronal apoptosis are major causes of poor outcomes after subarachnoid hemorrhage (SAH). Pterostilbene (PTE), an analog of resveratrol, has been verified as a potent sirtuin 1 (SIRT1) activator. However, the beneficial actions of PTE on SAH-induced brain injury and whether PTE regulates SIRT1 signaling after SAH remain unknown. We first evaluated the dose-response influence of PTE on early brain impairment after SAH. In addition, EX527 was administered to suppress SIRT1 signaling. The results revealed that PTE significantly attenuated microglia activation, oxidative insults, neuronal damage, and early neurological deterioration. Mechanistically, PTE effectively enhanced SIRT1 expression and promoted nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation in nuclei. Furthermore, EX527 pretreatment distinctly repressed PTE-induced SIRT1 and Nrf2 activation and deteriorated these beneficial outcomes. In all, our study provides the evidence that PTE protects against SAH insults by activating SIRT1-dependent Nrf2 signaling pathway. PTE might be a therapeutic alternative for SAH.

The relationship between fear of recurrence and depression in patients with cancer: The role of invasive rumination and catastrophizing.

Objective: To examine the relationship between fear of recurrence and depression in patients with cancer. Materials and methods: Two hundred and fifty-nine participants completed self-report questionnaires, including the Fear of Progression Questionnaire-Short Form, Rumination Inventory, Cognitive Emotion Regulation Questionnaire (Chinese version), and Center for Epidemiological Studies Depression Scale. Results: Fear of recurrence in patients with cancer was moderate, and the level of depression was significantly higher than that in the normal population. Fear of recurrence, invasive rumination, catastrophizing, and depression in patients with cancer were significantly positively correlated. The level of fear of recurrence was a significant positive predictor of the level of depression. Invasive rumination played a partial mediating role between fear of recurrence and depression; that is, fear of recurrence directly affected depression, and fear of recurrence indirectly affected depression through invasive rumination. Catastrophizing played a moderating role in the mediation model, in which fear of recurrence affected depression through invasive rumination. Conclusion: Invasive rumination plays a mediating role between fear of recurrence and depression in patients with cancer. Catastrophizing moderates the relationship between fear of recurrence and depression as well as the relationship between invasive rumination and depression.

The relationship between childhood trauma and post-traumatic growth among college students: The role of acceptance and positive reappraisal.

Objective: To examine the relationship among childhood trauma, acceptance, positive reappraisal and post-traumatic growth (PTG) among college students. Methods: Research participants were selected by random cluster sampling. 1,028 college students (62.6% female, 30.5% only-children) from 8 universities were investigated using manuscript-pencil survey versions of Childhood Trauma Questionnaire-Short Form (CTQ-SF), Cognitive emotion regulation questionnaire-Chinese version (CERQ-C) and Post traumatic Growth Inventory (PTGI). Results: Traumatic childhood experience significantly negatively predicts post traumatic growth in college students. Exposure to traumatic experiences in childhood can directly negatively predict post-traumatic growth and indirectly positively predict post traumatic growth via acceptance. Conclusion: Acceptance plays a mediating role between childhood traumatic experience and post traumatic growth. The mediating effect of acceptance is moderated by the positive reappraisal. When individuals have a lower level of positive reappraisal, the mediating effect between traumatic experience and post traumatic growth is significant. Several clinical implications for clinical psychology and psychological intervention are highlighted. Starting with changing individual cognition and helping individuals adopt positive cognitive emotion regulation strategies can help individuals actively reevaluate traumatic experience, so as to gain better and faster counseling results.

Isoliquiritigenin mitigates oxidative damage after subarachnoid hemorrhage in vivo and in vitro by regulating Nrf2-dependent Signaling Pathway via Targeting of SIRT1.

BACKGROUND: Oxidative stress is a crucial factor leading to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). Isoliquiritigenin has been verified as a powerful anti-oxidant in a variety of diseases models and can activate sirtuin 1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, the effects of isoliquiritigenin against EBI after SAH and the underlying mechanisms remain elusive. PURPOSE: The primary goal of this study is to verify the therapeutic effects of isoliquiritigenin on EBI after SAH and the possible molecular mechanisms. STUDY DESIGN: A prechiasmatic cistern SAH model in rats and a hemoglobin incubation SAH model in primary neurons were established. Isoliquiritigenin was administered after SAH induction. EX527 was employed to inhibit sirtuin 1 activation and ML385 was used to suppress Nrf2 signaling. METHODS: In our study, neurological scores, brain edema, biochemical estimation, western blotting, and histopathological study were performed to explore the therapeutic action of isoliquiritigenin against SAH. RESULTS: Our data revealed that isoliquiritigenin significantly mitigated oxidative damage after SAH as evidenced by decreased reactive oxygen species overproduction and enhanced intrinsic anti-oxidative system. Concomitant with the reduced oxidative insults, isoliquiritigenin improved neurological function and reduced neuronal death in the early period after SAH. Additionally, isoliquiritigenin administration significantly enhanced Nrf2 and sirtuin 1 expressions. Inhibition of Nrf2 by ML385 reversed the anti-oxidative and neuroprotective effects of isoliquiritigenin against SAH. Moreover, inhibiting sirtuin 1 by EX527 pretreatment suppressed isoliquiritigenin-induced Nrf2-dependent pathway and abated the cerebroprotective effects of isoliquiritigenin. In primary cortical neurons, isoliquiritigenin treatment also ameliorated oxidative insults and repressed neuronal degeneration. The beneficial aspects of isoliquiritigenin were attributed to the promotion of sirtuin 1 and Nrf2 signaling pathways and were counteracted by EX527. CONCLUSION: Our findings suggest that isoliquiritigenin exerts cerebroprotective effects against SAH-induced oxidative insults by modulating the Nrf2-mediated anti-oxidant signaling in part through sirtuin 1 activation. Isoliquiritigenin might be a new potential drug candidate for SAH.

In vitro Cartilage Regeneration Regulated by a Hydrostatic Pressure Bioreactor Based on Hybrid Photocrosslinkable Hydrogels.

Because of the superior characteristics of photocrosslinkable hydrogels suitable for 3D cell-laden bioprinting, tissue regeneration based on photocrosslinkable hydrogels has become an important research topic. However, due to nutrient permeation obstacles caused by the dense networks and static culture conditions, there have been no successful reports on in vitro cartilage regeneration with certain thicknesses based on photocrosslinkable hydrogels. To solve this problem, hydrostatic pressure (HP) provided by the bioreactor was used to regulate the in vitro cartilage regeneration based on hybrid photocrosslinkable (HPC) hydrogel. Chondrocyte laden HPC hydrogels (CHPC) were cultured under 5 MPa HP for 8 weeks and evaluated by various staining and quantitative methods. Results demonstrated that CHPC can maintain the characteristics of HPC hydrogels and is suitable for 3D cell-laden bioprinting. However, HPC hydrogels with concentrations over 3% wt% significantly influenced cell viability and in vitro cartilage regeneration due to nutrient permeation obstacles. Fortunately, HP completely reversed the negative influences of HPC hydrogels at 3% wt%, significantly enhanced cell viability, proliferation, and extracellular matrix (ECM) deposition by improving nutrient transportation and up-regulating the expression of cartilage-specific genes, and successfully regenerated homogeneous cartilage with a thickness over 3 mm. The transcriptome sequencing results demonstrated that HP regulated in vitro cartilage regeneration primarily by inhibiting cell senescence and apoptosis, promoting ECM synthesis, suppressing ECM catabolism, and ECM structure remodeling. Evaluation of in vivo fate indicated that in vitro regenerated cartilage in the HP group further developed after implantation and formed homogeneous and mature cartilage close to the native one, suggesting significant clinical potential. The current study outlines an efficient strategy for in vitro cartilage regeneration based on photocrosslinkable hydrogel scaffolds and its in vivo application.

Circ_0005918 Sponges miR-622 to Aggravate Intervertebral Disc Degeneration.

Intervertebral discdegeneration (IDD) is the most common cause of lower back pain, but the exact molecular mechanism of IDD is still unknown. Recently, studies have shown that circular RNAs (circRNAs) regulate diverse biological procedures such as cell metastasis, growth, metabolism, migration, apoptosis, and invasion. We demonstrated that IL-1ß and TNF-α induced circ_0005918 expression in the NP cell, and circ_0005918 was overexpressed in the IDD group compared with the control group. Moreover, the upregulated expression of circ_0005918 was associated with disc degeneration degree. The elevated expression of circ_0005918 promoted cell growth and ECM degradation, and it induced secretion of inflammatory cytokines including IL-1ß, IL-6, and TNF-α. Moreover, we found that circ_0005918 sponged miR-622 in the NP cell. In addition, the exposure to IL-1ß and TNF-α suppressed the expression of miR-622, which was downregulated in the IDD group compared with the control group. Furthermore, the downregulated expression of miR-622 was associated with disc degeneration degree. The expression level of miR-622 was negatively associated with circ_0005918 expression in the IDD group. In conclusion, circ_0005918 regulated cell growth, ECM degradation, and secretion of inflammatory cytokines by regulating miR-622 expression. These data suggested that circ_0005918 played important roles in the development of IDD via sponging miR-622.

Comparison of Enterprise stent 2 with 1 in assisting coiling of ruptured aneurysms: a real-world study.

Aim: To investigate the effectiveness and safety of the Enterprise 2 (E2) stent versus the Enterprise 1 (E1) stent in treating ruptured intracranial aneurysms (RIAs) in China. Materials & methods: The authors conducted an electronic medical record analysis for patients with RIAs who underwent E1/E2 deployment. The main outcomes were immediate complete occlusion (ICO), patient functional outcomes, complications and aneurysm recurrence. Results: Stent deployment was successful in all patients (E2: 90; E1: 270). ICO and patients with good functional outcomes at discharge were similar between E2 and E1 (80.0% vs 75.1% and 78.7% vs 81.1%, respectively). The E2 group had a significantly lower complication rate compared with the E1 group (7.8% vs 16.4%; odds ratio: 0.36; 95% CI: 0.15-0.91; p = 0.031). By 6 months post-discharge, the two groups had comparable patient functional outcomes and aneurysm recurrence (E2 vs E1: 80.2% vs 81.9% and 13.3% vs 14.9%). Conclusion: Compared with the E1 stent, the E2 stent had similar effectiveness but a lower complication risk in treating RIAs.