Qingjie Chen

Objective Cardiovascular diseases (CVDs) are major public health problems that threaten the lives and health of individuals. The article has reviewed recent progresses about ferroptosis and ferroptosis-related intervention approaches for the treatment of CVDs and provided more references and strategies for targeting ferroptosis to prevent and treat CVDs. Methods A comprehensive review was conducted using the literature researches. Results and discussion Many ferroptosis-targeted compounds and ferroptosis-related genes may be prospective targets for treating CVDs and our review provides a solid foundation for further studies about the detailed pathological mechanisms of CVDs. Conclusion There are challenges and limitations about the translation of ferroptosis-targeted potential therapies from experimental research to clinical practice. It warrants further exploration to pursure safer and more effective ferroptosis-targeted thereapeutic approaches for CVDs. Graphical Abstract

As a difficult-to-treat neurological condition, cerebral ischemia is currently limited to treatments such as intravenous recombinant tissue plasminogen activator thrombolysis and thrombectomy. Metformin, a potent antidiabetic drug, has been reported to have an independent function in enhancing the prognosis of stroke patients, in addition to its glucose-lowering effects. However, the mechanism of action of metformin in this context remains unclear. In vivo, a rat model of permanent middle cerebral artery occlusion was established, and after administration of a low dose of 10.5 mg/mL metformin, infarct area was measured by TTC staining, and cortical blood flow was determined by laser Doppler imaging. In vitro, the study established human umbilical vein endothelial cells treated with cobalt chloride. Immunofluorescence, immunohistochemistry, and Western blot experiments were performed to observe the expression of angiogenic factors, tight junction proteins, and apoptotic factors. A TUNEL assay was utilized to appraise cell death by apoptosis. A tube formation assay and scratch assay were conducted to determine the endothelial neovascularization status. Animal experiments have revealed that the administration of the AMPK activator metformin significantly reduced the infarct area, promoted the expression of angiogenic factors, and maintained the stability of tight junction proteins in endothelial cells. Moreover, metformin reduces nerve cells apoptosis by affecting the expression of the apoptotic protein cleaved-caspase3 via the HIF-1α pathway. In vitro, the LKB1/AMPK signaling pathway is activated after hypoxic stimulation, attaining its peak within the early stages of hypoxia (1–12 h) and gradually weakening thereafter. The administration of AMPK pharmacological agonists (between 36 and 48 h) can enhance AMPK activity, which can lead to the expression of angiogenic factors, maintain the stability of tight-junction proteins in endothelial cells, and facilitate endothelial cell migration and vascular structure formation. Conversely, the AMPK inhibitors exert the opposite effects. The activation of the LKB1/AMPK/HIF-1α signaling pathway by metformin in cerebral ischemia contributes to angiogenesis, promotes tissue repair in the injured area, and enhances neurologically functional symptoms.

Purpose. Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. Methods. We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. Results. We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [−0.68, −0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [−1.2, −0.43]), and HbA1c (SMD: 0.34; 95% CI [−0.48, −0.21]). All data were statistically significant ( P < 0.0001 ). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. Conclusion. DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals’ cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0–180 days. This trial is registered with CRD42023399473.

Clinical and epidemiological research shows that people with diabetes mellitus frequently experience diabetic cognitive impairment. Schisandrin A (SchA), one of the lignans found in the dried fruit of Schisandra chinensis, has a variety of pharmacological effects on immune system control, apoptosis suppression, anti-oxidation and anti-inflammation. The goal of the current investigation was to clarify the probable neuro-protective effects of SchA against streptozotocin-induced diabetes deficiencies of the spatial learning and memory in rats. The outcomes show that SchA therapy effectively improved impaired glucose tolerance, fasting blood glucose level and serum insulin level in diabetic rats. Additionally, in the Morris water maze test, diabetic rats showed deficits in spatial learning and memory that were ameliorated by SchA treatment. Moreover, giving diabetic rats SchA reduced damage to the hippocampus structure and increased the production of synaptic proteins. Further research revealed that SchA therapy reduced diabetic-induced hippocampus neuron damage and the generation of Aβ, as demonstrated by the upregulated phosphorylation levels of insulin signaling pathway connected proteins and by the decreased expression levels of inflammatory-related factors. Collectively, these results suggested that SchA could improve diabetes-related impairments in spatial learning and memory, presumably by reducing inflammatory responses and regulating the insulin signaling system.

Protein‒protein, protein‒RNA, and protein‒DNA interaction networks form the basis of cellular regulation and signal transduction, making it crucial to explore these interaction networks to understand complex biological processes. Traditional methods such as affinity purification and yeast two-hybrid assays have been shown to have limitations, as they can only isolate high-affinity molecular interactions under nonphysiological conditions or in vitro. Moreover, these methods have shortcomings for organelle isolation and protein subcellular localization. To address these issues, proximity labeling techniques have been developed. This technology not only overcomes the limitations of traditional methods but also offers unique advantages in studying protein spatial characteristics and molecular interactions within living cells. Currently, this technique not only is indispensable in research on mammalian nucleoprotein interactions but also provides a reliable approach for studying nonmammalian cells, such as plants, parasites and viruses. Given these advantages, this article provides a detailed introduction to the principles of proximity labeling techniques and the development of labeling enzymes. The focus is on summarizing the recent applications of TurboID and miniTurbo in mammals, plants, and microorganisms.

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes’s impairment of spatial learning memory.Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35 mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines.Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide.Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.