Research trends and hotspots of ferroptosis in neurodegenerative diseases from 2013 to 2023: A bibliometrics study.

Background: With the aging population, the incidence of neurodegenerative diseases increases yearly, seriously impacting human health. Various journals have published studies on the pathogenesis of ferroptosis in neurodegenerative diseases. However, bibliometric analysis in this field is still lacking. The study aims to visually analyze global research trends in this field over the past decade. Methods: The articles and reviews regarding ferroptosis in neurodegenerative diseases were retrieved from the Web of Science on September 1, 2023. Citespace [version 6.2. R4 (64-bit)] and VOSviewer (version 1.6.18) were used to conduct the bibliometric and knowledge-map analysis. Results: In total, 370 studies were included in the paper and ranked by their citation frequency. Many articles on ferroptosis in neurodegenerative diseases have been published in the past decade. The country, institution, author, and journal with the highest publications were China, Guangzhou Medical University, Maher, Pamela, and Free Radical Biology And Medicine, respectively. The analysis of keyword co-occurrence indicated that research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases, especially a few key pathways that triggered ferroptosis in these diseases, including lipid peroxidation signaling, iron metabolism, and GSH/GPX4 signaling. In addition, ferroptosis inhibitors such as liproxstatins and ferrostatins had protective effects in animal models of neurodegenerative diseases. Therefore, future attention should also be focused on therapeutic drugs that target ferroptosis. Conclusion: This study comprehensively analyzed the publications on ferroptosis in neurodegenerative diseases from a bibliometric perspective. Research on this topic is currently expanding at a rapid pace, and the China holds a leading position in this field by its scientific achievements and productivity. Moreover, the research frontiers were molecular mechanisms of ferroptosis in neurodegenerative diseases and developing targeted therapeutic drugs. In summary, our results showed an all-sided overview of the knowledge atlas and a valuable reference for the future research in this field.

Knowledge domain and trend of disease-modifying therapies for multiple sclerosis: A study based on CiteSpace.

Objective: To explore the current status and trends of disease-modifying therapies (DMTs) for multiple sclerosis through bibliometric and visual analyses of the related literature. Methods: Relevant literature from the Web of Science Core Collection from 2017 to 2022 was retrieved, and a bibliometric analysis was performed using CiteSpace 6.1. R2. Thesoftware was used to generate visual graphs of the author, institution, country, keyword co-occurrence, and literature co-citation network. Results: A total of 1719 manuscripts were retrieved, including 1397 original studies and 322 reviews. In the past five years, Patti F and the University of London were the authors and institutions generating the largest number of publications, respectively, and there was active collaboration between authors and institutions. The United States was the largest contributor to the relevant literature, and the high-frequency keywords in the field of multiple sclerosis disease-modifying therapies in the past five years mainly included multiple sclerosis, disease-modifying therapy, double-blind, disability, natalizumab, effectiveness, fingolimod, glatiramer acetate, and dimethyl fumarate. Conclusions: Current research hotspots and trends in DMTs in multiple sclerosis focus on the effectiveness of different DMTs drugs in treating patients with MS and how to optimise treatment strategies. In the context of the COVID-19 pandemic, the correlation between MS and COVID-19 infection and the method to manage and address the adverse effects of DMTs on multiple sclerosis patients is also future research trends.

Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy.

Ischemia/reperfusion (I/R) injury is a pathological event that results in reperfusion due to low blood flow to an organ. Cerebral ischemia is a common cerebrovascular disease with high mortality, and reperfusion is the current standard intervention. However, reperfusion may further induce cellular damage and dysfunction known as cerebral ischemia/reperfusion injury (CIRI). Currently, strategies for the clinical management of CIRI are limited, necessitating the exploration of novel and efficacious treatment modalities for the benefit of patients. PI3K/Akt signaling pathway is an important cellular process associated with the disease. Stimulation of the PI3K/Akt pathway enhances I/R injury in multiple organs such as heart, brain, lung, and liver. It stands as a pivotal signaling pathway crucial for diminishing cerebral infarction size and safeguarding the functionality of brain tissue after CIRI. During CIRI, activation of the PI3K/Akt pathway exhibits a protective effect on CIRI. Furthermore, activation of the PI3K/Akt pathway has the potential to augment the activity of antioxidant enzymes, resulting in a decrease in reactive oxygen species (ROS) and the associated oxidative stress. Meanwhile, PI3K/Akt plays a neuroprotective role by inhibiting inflammatory responses and apoptosis. For example, PI3K/Akt interacts with NF-κB, Nrf2, and MAPK signaling pathways to mitigate CIRI. This article is aimed to explore the pivotal role and underlying mechanism of PI3K/Akt in ameliorating CIRI and investigate the influence of ischemic preconditioning and post-processing, as well as the impact of pertinent drugs or activators targeting the PI3K/Akt pathway on CIRI. The primary objective is to furnish compelling evidence supporting the activation of PI3K/Akt in the context of CIRI, elucidating its mechanistic intricacies. By doing so, the paper aims to underscore the critical contribution of PI3K/Akt in mitigating CIRI, providing a theoretical foundation for considering the PI3K/Akt pathway as a viable target for CIRI treatment.

The role of NPY signaling pathway in diagnosis, prognosis and treatment of stroke.

Neuropeptide Y (NPY), an extensively distributed neurotransmitter within the central nervous system (CNS), was initially detected and isolated from the brain of a pig in 1982. By binding to its G protein-coupled receptors, NPY regulates immune responses and contributes to the pathogenesis of numerous inflammatory diseases. The hippocampus contained the maximum concentration in the CNS, with the cerebral cortex, hypothalamus, thalamus, brainstem, and cerebellum following suit. This arrangement suggests that the substance has a specific function within the CNS. More and more studies have shown that NPY is involved in the physiological and pathological mechanism of stroke, and its serum concentration can be one of the specific biomarkers of stroke and related complications because of its high activity, broad and complex effects. By summarizing relevant literature, this article aims to gain a thorough understanding of the potential clinical applications of NPY in the treatment of stroke, identification of stroke and its related complications, and assessment of prognosis.

Whether serum leptin and insulin-like growth factor-1 are predictive biomarkers for post-stroke depression: A meta-analysis and systematic review.

Leptin and insulin-like growth factor-1 (IGF-1) may play a role in clinical identification of post-stroke depression (PSD). Here, eight databases (including CNKI, Wanfang, SinoMed, VIP, PubMed, the Cochrane Library, Embase, and the Web of Science) were employed to search for studies on serum leptin and insulin-like growth factor-1 expression levels in patients with PSD. In total, 13 articles were included, of which 6 studies investigated the expression level of serum leptin in patients with PSD, 7 studies explored the serum IGF-1 in PSD patients. Then, the RevMan 5.4 software was used for meta-analysis. The results showed that serum leptin levels were significantly higher in PSD patients than in patients without PSD (SMD = 1.54, 95% CI: 0.84, 2.23; P = 0.006). The result of subgroup analysis showed that the serum leptin levels in PSD patients were significantly higher than those without PSD in acute phase (SMD = 1.38, 95% CI: 0.04, 2.71; P = 0.04), subacute phase (SMD = 2.31, 95% CI: 0.88, 3.73; P = 0.001), and chronic phase (SMD = 1.02, 95% CI: 0.43, 1.60; P = 0.0007); There was no significant difference in serum IGF-1 level between PSD patients and patients without PSD (SMD = 0.49, 95% CI: -0.55, 1.52; P = 0.36). Moreover, the subgroup analysis also showed that there was no statistical difference in acute stage (SMD = 0.36, 95% CI: 0.89, 1.60; P = 0.57). Our study provides evidence to prove that serum leptin level has potential clinical application value as biomarkers for identifying PSD.

MiR-135b-5p targets ADAM12 to suppress invasion and accelerate trophoblast apoptosis in preeclampsia.

INTRODUCTION: Preeclampsia was a serious complication often leaded to adverse pregnancy outcomes. Abnormal placental miR-135b-5p expression in preeclampsia was observed in our preliminary investigation. However, the role of miR-135b-5p in preeclampsia was unclear. METHODS: We determined the miR-135b-5p expression pattern at the fetomaternal interface and levels in placental tissue and exosomes. MiR-135b-5p expression in the trophoblast cell line HTR8/SVneo was manipulated by transient agomir or antagomir transfection or establishment of HTR8/SVneo cell line stably overexpressing miR-135b or miR-135b-5p-sponger. Then the function of miR-135b-5p on the motility of HTR8/SVneo cells, and its effects on cell viability was determined. Finally, we confirmed the relationship between miR-135b-5p and ADAM12. RESULTS: MiR-135b-5p exclusively expressed in the villous cytotrophoblast, and extravillous trophoblast. Significant miR-135b-5p upregulation was observed in the placenta and peripheral plasma exosomes in preeclampsia, and could be a highly sensitive molecular marker for preeclampsia. Elevated miR-135b-5p expression significantly promoted apoptosis and inhibited HTR8/SVneo cell invasion and migration. Binding of miR-135b-5p to the ADAM12 mRNA 3'-untranslated region was predicted by bioinformatics analysis and confirmed using a dual-luciferase reporter assay. High miR-135-5p levels inhibit the invasion and migration of trophoblastic cells, possibly by directly binding to the 3'-UTR of DADM12 and suppressing its translation efficiency, thereby nullifying the promotion of trophoblast invasion and migration via ADAM12. DISCUSSION: Abnormal upregulation of miR-135b-5p may be involved in preeclampsia through triggering trophoblast apoptosis and impeding trophoblast invasion and migration by targeting ADAM12.

Role of traditional Chinese medicine monomers in cerebral ischemia/reperfusion injury:a review of the mechanism.

Ischemia/reperfusion (I/R) injury is a pathological process wherein reperfusion of an ischemic organ or tissue exacerbates the injury, posing a significant health threat and economic burden to patients and their families. I/R triggers a multitude of physiological and pathological events, such as inflammatory responses, oxidative stress, neuronal cell death, and disruption of the blood-brain barrier (BBB). Hence, the development of effective therapeutic strategies targeting the pathological processes resulting from I/R is crucial for the rehabilitation and long-term enhancement of the quality of life in patients with cerebral ischemia/reperfusion injury (CIRI). Traditional Chinese medicine (TCM) monomers refer to bioactive compounds extracted from Chinese herbal medicine, possessing anti-inflammatory and antioxidative effects, and the ability to modulate programmed cell death (PCD). TCM monomers have emerged as promising candidates for the treatment of CIRI and its subsequent complications. Preclinical studies have demonstrated that TCM monomers can enhance the recovery of neurological function following CIRI by mitigating oxidative stress, suppressing inflammatory responses, reducing neuronal cell death and functional impairment, as well as minimizing cerebral infarction volume. The neuroprotective effects of TCM monomers on CIRI have been extensively investigated, and a comprehensive understanding of their mechanisms can pave the way for novel approaches to I/R treatment. This review aims to update and summarize evidence of the protective effects of TCMs in CIRI, with a focus on their role in modulating oxidative stress, inflammation, PCD, glutamate excitotoxicity, Ca2+ overload, as well as promoting blood-brain barrier repairment and angiogenesis. The main objective is to underscore the significant contribution of TCM monomers in alleviating CIRI.

IL-33/ST2 signaling pathway and Alzheimer's disease: A systematic review and meta-analysis.

The IL-33/ST2 signaling pathway has potential relevance for clinical identification and treatment of Alzheimer's disease (AD). Here, eight databases (including CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane library, Embase and Web of Science) were employed to search for studies on IL-33/ST2 signaling pathway and its association with AD. Totally, 15 articles were included, of which 5 studies investigated the connection between IL-33 gene polymorphisms and AD, 4 studies explored the serum IL-33 and sST2 levels in patients with AD and Mild cognitive impairment (MCI), and the exact mechanisms underlying IL-33/ST2 signaling pathway in AD were explored in 6 studies. Then, the RevMan 5.4 software was used for meta-analysis, and the related studies were systematically reviewed. The results of the meta-analysis showed that serum IL-33 levels were higher in patients with AD and MCI than in healthy controls (HC), with serum IL-33 levels in AD patients significantly higher than in MCI patients (SMD = 0.26, 95 % CI: 0.02, 0.51; P = 0.04). Compared with HC, the sST2 level was significantly higher in AD patients (SMD = 1.23, 95 % CI: 0.93, 1.53; P < 0.00001) and tended to elevate in patients with MCI. The systematic review indicated that there is a significant relationship between IL-33 gene polymorphisms and susceptibility to AD; The IL-33/ST2 signaling pathway may be one of the future treatment targets for AD. Our study provides evidence to prove that serum IL-33 and sST2 have potential clinical application value as biomarkers for identifying AD.

Design and Characterization of HY-038 Solid Dispersions via Spray Drying Technology: In Vitro and In Vivo Evaluations.

The aim of this study was to prepare HY-038 solid dispersions (SDs) with single carrier at high drug loading and then forming a tablet to enhance solubility, dissolution, and bioavailability via spray drying technology. At the same time, we hope to develop a more convenient in vitro method to predict the absorption behavior of different formulations in vivo. Different solid dispersions, varying in drug/polymer ratios, were prepared. Infrared spectroscopy, differential scanning calorimetry, scanning electron microscope, and X-ray diffraction were used to perform solid-state characterizations of the pure drug and SDs. Contact angle of water, dissolution in pH = 6.8 phosphate buffer, and in vivo absorption in dogs were studied. As a result, solid-state characterization demonstrated the transformation of the crystalline HY-038 to an amorphous state in the solid dispersions, and the in vivo exposure followed with the trend of the dissolution curve combined with contact angle. Compared with the prototype formulation, the Cmax and AUC0-∞ of optimized formulation SD2 (HY-038-HPMCAS 3:1) increased by about 5 ~ 9 times at the same dose. More importantly, the SD2 formulation showed approximately linear increases in Cmax and AUC0-∞ as the dose increased from 50 to 100 mg, while the prototype formulation reached absorption saturation at 50 mg. SD2 (HY-038-HPMCAS 3:1) was selected as the best formulation for the downstream development.

Up-regulation of ROR2 is associated with unfavorable prognosis and tumor progression in cervical cancer.

AIMS: To investigate the clinical significance of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in cervical cancer. METHODS: We examined ROR2 levels in 8 pairs of surgically resected cervical cancer and adjacent normal cervical tissues by real-time PCR. Moreover, we performed immunohistochemistry to examine ROR2 expression in 94 paraffin-embedded cervical cancer samples and analyzed the association between ROR2 expression, clinicopathologic factors and prognosis. RESULTS: ROR2 expression was up-regulated in cervical cancer tissues compared with adjacent normal cervix. In paraffin-embedded cervical cancer samples, high expression of ROR2 was shown in 40 (42.6%) of 94 cases, also, it was significantly associated with tumor stage (P = 0.018) and lymph nodes metastasis (P = 0.013). Moreover, survival analysis showed that ROR2 expression was an independent prognostic factor of poor overall and recurrent free survival (P = 0.045 and 0.001, respectively). CONCLUSION: These results indicate that ROR2 is significantly correlated with cancer progression and poor prognosis in cervical cancer.

[Auditory event-related potentials in children with functional articulation disorders].

OBJECTIVE: To investigate the central auditory processing function in children with functional articulation disorders (FAD), and possible causes of FAD. METHODS: Twenty-seven children with FAD were selected as the case group and 50 age-matched normal children were selected as the control group. The two groups were compared with respect to the following factors: percentage of individuals with a positive history of language development disorder, and the form, peak latency and peak amplitude of mismatch negativity (MMN) on auditory event-related potentials. RESULTS: Compared with the control group, the case group had a significantly higher percentage of individuals with a positive history of language development disorder (70% vs 8%; P<0.01), a significantly prolonged peak latency of MMN (209 ± 31 ms vs 175 ± 32 ms; P<0.01), and an insignificantly lower peak amplitude of MMN (P>0.05). CONCLUSIONS: Prolonged central auditory processing may be one of the causes of FAD in children.

The effects and outcomes of electrolyte disturbances and asphyxia on newborns hearing.

OBJECTIVE: To determine the effect of electrolyte disturbances (ED) and asphyxia on infant hearing and hearing outcomes. STUDY DESIGN: We conducted newborn hearing screening with transient evoked otoacoustic emission (TEOAE) test on a large scale (>5000 infants). The effects of ED and asphyxia on infant hearing and hearing outcomes were evaluated. RESULT: The pass rate of TEOAE test was significantly reduced in preterm infants with ED (83.1%, multiple logistic regression analysis: P<0.01) but not in full-term infants with ED (93.6%, P=0.41). However, there was no significant reduction in the pass rate in infants with asphyxia (P=0.85). We further found that hypocalcaemia significantly reduced the pass rate of TEOAE test (86.8%, P<0.01). In the follow-up recheck at 3 months of age, the pass rate remained low (44.4%, P<0.01). CONCLUSION: ED is a high-risk factor for preterm infant hearing. Hypocalcaemia can produce more significant impairment with a low recovery rate.

[Study on purification of 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from Polygonum multiflori].

OBJECTIVE: To study the conditions and parameters of purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from Polygonum multiflori. METHOD: Absorption capacity of four resins for 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside was compared. With the adsorption ability as indexes, the process of absorbing and purifying 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glycoside from P. multiflori with S-8 macroporous resin absorbent was selected by orthogonal design. RESULT: The S-8 resin was the best of the four resins. The optimum process condition was 50% ethanol as eluting solvent, the flow rate at 1.5 mL x min(-1), pH at 7-8, and the solution concentration at 0.2 g x mL(-1). The absorption capacity by this process was 36.89 mg x g(-1). CONCLUSION: The process is simple and convenient and the regeneration of resin is easy, so this method of purification is advisable.