Ferroptosis: A new strategy for targeting Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a complex pathogenesis, which involves the formation of amyloid plaques and neurofibrillary tangles. Many recent studies have revealed a close association between ferroptosis and the pathogenesis of AD. Factors such as ferroptosis-associated iron overload, lipid peroxidation, disturbances in redox homeostasis, and accumulation of reactive oxygen species have been found to contribute to the pathological progression of AD. In this review, we explore the mechanisms underlying ferroptosis, describe the link between ferroptosis and AD, and examine the reported efficacy of ferroptosis inhibitors in treating AD. Finally, we discuss the potential challenges to ferroptosis inhibitors use in the clinic, enabling their faster use in clinical treatment.

A New Perspective in the Treatment of Ischemic Stroke: Ferroptosis.

Ischemic stroke is a common neurological disease. Currently, there are no Food and Drug Administration-approved drugs that can maximize the improvement in ischemic stroke-induced nerve damage. Hence, treating ischemic stroke remains a clinical challenge. Ferroptosis has been increasingly studied in recent years, and it is closely related to the pathophysiological process of ischemic stroke. Iron overload, reactive oxygen species accumulation, lipid peroxidation, and glutamate accumulation associated with ferroptosis are all present in ischemic stroke. This article focuses on describing the relationship between ferroptosis and ischemic stroke and summarizes the relevant substances that ameliorate ischemic stroke-induced neurological damage by inhibiting ferroptosis. Finally, the problems in the treatment of ischemic stroke targeting ferroptosis are discussed, hoping to provide a new direction for its treatment.

Simultaneous determination of twenty-nine active compounds in fuzhengjiedu granules by HPLC-QQQ-MS/MS.

As an empirical medicine of traditional Chinese medicine, Fuzhengjiedu Granules have shown an effect against COVID-19 in clinical and inflammatory animal models. It is formulated with eight herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Glycyrrhizae Radix Et Rhizoma, Lonicerae Japonicae Flos, Gleditsiae Spina, Fici Radix, Pogostemonis Herba, and Citri Reticulatae Pericarpium. This study established a high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS) method by simultaneously determining 29 active compounds in the granules with significant content differences. Separation by gradient elution using acetonitrile and water (0.1% formic acid) as mobile phases was performed on a Waters Acquilty UPLC T3 column (2.1 mm × 100 mm, 1.7 µm). A triple quadrupole mass spectrometer, operating in positive and negative ionization modes, was used for multiple reaction monitoring to detect the 29 compounds. All calibration curves showed good linear regression (r2 > 0.998). RSDs of precision, reproducibility, and stability of active compounds were all lower than 5.0%. The recovery rates were 95.4-104.9%, with RSDs< 5.0%. This method was successfully used to analyze the samples, and the results showed that 26 representative active components from 8 herbs were detected in the granules. While aconitine, mesaconitine, and hypaconitine were not detected, indicating that the existing samples were safe. The granules had the maximum and minimum content of hesperidin (27.3 ± 0.375 mg/g) and benzoylaconine (38.2 ± 0.759 ng/g). To conclude, a fast, accurate, sensitive, and reliable HPLC-QQQ-MS/MS method was established, which can simultaneously detect 29 active compounds that have a considerable difference in the content of Fuzhengjiedu Granules. This study can be used to control the quality and safety of Fuzhengjiedu Granules and provide a basis and guarantee for further experimental research and clinical application.

Ferroptosis is a new therapeutic target for spinal cord injury.

Spinal cord injury is a serious traumatic disease. As Ferroptosis has been increasingly studied in recent years, it has been found to be closely related to the pathophysiological processes of spinal cord injury. Iron overload, reactive oxygen species accumulation, lipid peroxidation and glutamate accumulation associated with Ferroptosis are all present in spinal cord injury, and thus Ferroptosis is thought to be involved in the pathological processes secondary to spinal cord injury. This article highlights the relationship between Ferroptosis and spinal cord injury, lists substances that improve spinal cord injury by inhibiting Ferroptosis, and concludes with a discussion of the problems that may be encountered in the clinical translation of Ferroptosis inhibitors as a means of enabling their faster use in clinical treatment.

Improvement of human embryonic stem cell-derived retinal pigment epithelium cell adhesion, maturation, and function through coating with truncated recombinant human vitronectin.

AIM: To explore an xeno-free and defined coating substrate suitable for the culture of H9 human embryonic stem cell-derived retinal pigment epithelial (hES-RPE) cells in vitro, and compare the behaviors and functions of hES-RPE cells on two culture substrates, laminin521 (LN-521) and truncated recombinant human vitronectin (VTN-N). METHODS: hES-RPE cells were used in the experiment. The abilities of LN-521 and VTN-N at different concentrations to adhere to hES-RPE cells were compared with a high-content imaging system. Quantitative real-time polymerase chain reaction was used to evaluate RPE-specific gene expression levels midway (day 10) and at the end (day 20) of the time course. Cell polarity was observed by immunofluorescent staining for apical and basal markers of the RPE. The phagocytic ability of hES-RPE cells was identified by flow cytometry and immunofluorescence. RESULTS: The cell adhesion assay showed that the ability of LN-521 to adhere to hES-RPE cells was dose-dependent. With increasing coating concentration, an increasing number of cells attached to the surface of LN-521-coated wells. In contrast, VTN-N presented a strong adhesive ability even at a low concentration. The optimal concentration of LN-521 and VTN-N required to coat and adhesion to hES-RPE cells were 2 and 0.25 µg/cm2, respectively. Furthermore, both LN-521 and VTN-N could facilitate adoption of the desired cobblestone cellular morphology with tight junction and showed polarity by the hES-RPE cells. However, hES-RPE cells cultivated in VTN-N had a greater phagocytic ability, and it took less time for these hES-RPE cells to mature. CONCLUSION: VTN-N is a more suitable coating substrate for cultivating hES-RPE cells.

Evaluation of Intraarterial Thrombolysis in Treatment of Cosmetic Facial Filler-Related Ophthalmic Artery Occlusion.

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy. METHODS: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSIONS: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.