Astrocyte modulation in cerebral ischemia-reperfusion injury: A promising therapeutic strategy.

Cerebral ischemia-reperfusion injury (CIRI) poses significant challenges for drug development due to its complex pathogenesis. Astrocyte involvement in CIRI pathogenesis has led to the development of novel astrocyte-targeting drug strategies. To comprehensively review the current literature, we conducted a thorough analysis from January 2012 to December 2023, identifying 82 drugs aimed at preventing and treating CIRI. These drugs target astrocytes to exert potential benefits in CIRI, and their primary actions include modulation of relevant signaling pathways to inhibit neuroinflammation and oxidative stress, reduce cerebral edema, restore blood-brain barrier integrity, suppress excitotoxicity, and regulate autophagy. Notably, active components from traditional Chinese medicines (TCM) such as Salvia miltiorrhiza, Ginkgo, and Ginseng exhibit these important pharmacological properties and show promise in the treatment of CIRI. This review highlights the potential of astrocyte-targeted drugs to ameliorate CIRI and categorizes them based on their mechanisms of action, underscoring their therapeutic potential in targeting astrocytes.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

Insights into Thiourea-Based Bifunctional Catalysts for Efficient Conversion of CO2 to Cyclic Carbonates.

The bifunctional thiourea catalyst system with both electrophilic and nucleophilic centers has been certified to be effective for fixing CO2 under mild reaction conditions; however, many questions remain, especially concerning the relationship between structure and performance. Herein, we systematically studied a series of such bifunctional catalysts with different chain lengths, nucleophilic anions, and substituents, which impact obvious influence on the catalytic performance. The activation energies of catalysts with different chain lengths are calculated via in situ IR. On this basis, we disclosed for the first time that the spacer length of tetramethylene -(CH2)6- is the optimal spatial effect for the coupling of epoxides and CO2. Particularly, the single crystal X-ray diffraction analysis of the molecular structures of the bifunctional catalyst C8 indicated the discovery of the existence of interaction force between the sulfur atom on the thiourea group and one hydrogen atom on the benzene ring, as well as the intermolecular hydrogen bonding interaction of the bromide (Br-) and two NH groups on the thiourea group. The catalyst structure performance, direct observation of the crystal structure, the thermodynamic study, and a wide range of substrates (12 examples) should be informative on the optimization of the existing catalysts or the design of new catalysts in the future.

Regulatory role of miR-129 and miR-384-5p on apoptosis induced by oxygen and glucose deprivation in PC12 cell.

This study aimed to establish the role of miR-129 and miR-384-5p in cerebral ischemia-induced apoptosis. Using PC12 cells transfected with miR-129 or miR-384-5p mimics or inhibitors, oxygen glucose deprivation (OGD) conditions were applied for 4 h to simulate transient cerebral ischemia. Apoptotic phenotypes were assessed via lactate dehydrogenase (LDH) assay, MTT cell metabolism assay, and fluorescence-activated cell sorting (FACS). The effect of miR overexpression and inhibition was evaluated by protein and mRNA detection of bcl-2 and caspase-3, critical apoptosis factors. Finally, the direct relationship of miR-129 and bcl-2 and miR-384-5p and caspase-3 was measured by luciferase reporter assay. The overexpression of miR-384-5p and miR-129 deficiency significantly enhanced cell viability, reduced LDH release, and inhibited apoptosis. By contrast, overexpression of miR-129 and miR-384-5p deficiency aggravated hypoxia-induced apoptosis and cell injury. miR-129 overexpression significantly reduced mRNA and protein levels of bcl-2 and miR-129 inhibition significantly increased mRNA and protein levels of bcl-2 in hypoxic cells.miR-384-5p overexpression significantly reduced protein levels of caspase-3 while miR-384-5p deficiency significantly increased protein levels of caspase-3. However, no changes were observed in caspase-3 mRNA in either transfection paradigm. Finally, luciferase reporter assay confirmed caspase-3 to be a direct target of miR-384-5p; however, no binding activity was detected between bcl-2 and miR-129.Transient cerebral ischemia induces differential expression of miR-129 and miR-384-5p which influences apoptosis by regulating apoptotic factors caspase-3 and bcl-2, thereby participating in the pathological mechanism of cerebral ischemia, and becoming potential targets for the treatment of ischemic cerebral injury in the future.

Crosslinked Resin-Supported Bifunctional Organocatalyst for Conversion of CO2 into Cyclic Carbonates.

The development of solvent-free, metal-free, recyclable organic catalysts is required for the current chemical fixation of carbon dioxide converted into cyclic carbonates. With the goal of reducing the cost, time, and energy consumption for the coupling reaction of CO2 and epoxides, a series of highly active heterogeneous catalysts, based on a thiourea and quaternary ammonium salt system, are synthesized by using a thiol-ene click reaction under ultraviolet light. Benefitting from synergistic interactions of the electrophilic center (thiourea) and the nucleophilic site (ammonium bromide), the catalysts exhibit excellent catalytic selectivity (99 %) for the cycloaddition of carbon dioxide with a diverse range of epoxides under mild conditions (1.2 MPa, 100 °C). Moreover, the catalyst can be easily recycled by facile filtration and reused for 5 times without noticeable loss of activity and selectivity. This work provides a potential heterogeneous catalyst for the conversion of carbon dioxide into high value-added chemicals with the combined advantages of low cost, easy recovery, and satisfactory catalytic properties.

An in vivo molecular imaging probe (18)F-Annexin B1 for apoptosis detection by PET/CT: preparation and preliminary evaluation.

There is an increasing need to develop non-invasive molecular imaging strategies for visualizing and quantifying apoptosis status of diseases (especially for cancer) for diagnosis and monitoring treatment response. Since externalization of phosphatidylserine (PS) is one of the early molecular events during apoptosis, Annexin B1 (AnxB1), a member of Annexins family with high affinity toward the head group of PS, could be a potential positron emission tomography (PET) imaging probe for imaging cell death process after labeled by positron-emitting nuclides, such as (18)F. In the present study, we investigated a novel PET probe, (18)F-labeled Annexin B1 ((18)F-AnxB1), for apoptosis imaging. (18)F-AnxB1 was prepared reliably by conjugating AnxB1 with a (18)F-tag, N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB), in a radiolabeling yield of about 20 % within 40 min. The in vitro binding of (18)F-AnxB1 with apoptotic cells induced by anti-Fas antibody showed twofold increase compared to those without treatment, confirmed by flow cytometric analysis with AnxV-FITC/PI staining. Stability tests demonstrated (18)F-AnxB1 was rather stable in vitro and in vivo without degradation. The serial (18)F-AnxB1 PET/CT scans in healthy rats outlined its biodistribution and pharmacokinetics, indicating a rapid renal clearance and predominant accumulation into kidney and bladder at 2 h p.i. (18)F-AnxB1 PET/CT imaging was successfully applied to visualize in vivo apoptosis sites in tumor induced by chemotherapy and in kidney simulated by ischemia-reperfusion injury. The high-contrast images were obtained at 2 h p.i. to delineate apoptotic tumor. Apoptotic region could be still identified by (18)F-AnxB1 PET 4 h p.i., despite the high probe retention in kidneys. In summary, we have developed (18)F-AnxB1 as a PS-specific PET probe for the apoptosis detection and quantification which could have broad applications from disease diagnosis to treatment monitoring, especially in the cases of cancer.

Surgical management of aortoesophageal fistula caused by foreign bodies.

OBJECTIVE: Aortoesophageal fistula (AEF) is a rare complication of foreign-body ingestion but is often life threatening. METHODS: Between July 2006 and July 2009, four patients (two male and two female, age between 54 and 62 years old) with AEF were treated in our center. Cardiopulmonary bypass was established in all cases. The infected aorta was resected and replaced with aortic Dacron graft. The esophagus was mobilized and removed, and the digestive tract was reconstructed 1-2 months later after the first operation, by performing anastomosis of the esophagus and stomach at the neck. RESULTS: All four cases were treated successfully and survived up to the days when this article was written. CONCLUSIONS: It might be a safer way to perform this surgery under cardiopulmonary bypass. Thorough surgical debridement should be done, including resection of thoracic esophagus, adequate irrigation and flushing, and full draining of the chest cavity. Reconstruction of the digestive tract in the second stage of this two-stage operation should be the safest choice.