MetazExp: a database for gene expression and alternative splicing profiles and their analyses based on 53 615 public RNA-seq samples in 72 metazoan species.

RNA-seq has been widely used in experimental studies and produced a massive amount of data deposited in public databases. New biological insights can be obtained by retrospective analyses of previously published data. However, the barrier to efficiently utilize these data remains high, especially for those who lack bioinformatics skills and computational resources. We present MetazExp (https://bioinfo.njau.edu.cn/metazExp), a database for gene expression and alternative splicing profiles based on 53 615 uniformly processed publicly available RNA-seq samples from 72 metazoan species. The gene expression and alternative splicing profiles can be conveniently queried by gene IDs, symbols, functional terms and sequence similarity. Users can flexibly customize experimental groups to perform differential and specific expression and alternative splicing analyses. A suite of data visualization tools and comprehensive links with external databases allow users to efficiently explore the results and gain insights. In conclusion, MetazExp is a valuable resource for the research community to efficiently utilize the vast public RNA-seq datasets.

The More, the Better? Social Capital Profiles and Adolescent Internalizing Symptoms: A Latent Profile Analysis.

Past research suggests that offline and online social capital are empirically linked to adolescent psychological adjustment. However, little is known regarding the implications of distinctive combinations of social capital for adolescent internalizing symptoms. The present study aimed to examine adolescent social capital patterns and their associations with internalizing symptoms by using latent profile analysis. A cross-sectional web-based survey was conducted among 1595 Chinese adolescents (mean age = 14.30 years, 50.7% male). All adolescents completed self-report questionnaires on their perceived offline and online social capital, depressive symptoms and anxiety symptoms. Latent profile analysis revealed four profiles of social capital: (1) Low Social Capital, (2) Moderate Social Capital, (3) High Social Capital, and (4) Only High Offline Social Capital. Further, analysis of covariance demonstrated that the Only High Offline Social Capital profile had significantly fewer internalizing symptoms than other three profiles. No statistical differences of internalizing symptoms were found between the other three profiles, except that the Moderate Social Capital profile showed fewer anxiety symptoms than the Low Social Capital profile. These findings suggest that more social capital does not equal to better mental health status. The social capital profiles and their associations with adolescent internalizing symptoms may provide practitioners with meaningful implications regarding the role of offline and online social capital in adolescent psychological adjustment.

Who is the hardest to wake up from sleep? An investigation of self-reported sleep inertia using a latent profile analysis.

Few studies have assessed the overall nature and profiles of subjective sleep inertia (SI) within the general population. This study was designed to identify subjective SI profiles and examine the associations between profiles of subjective SI with sociodemographic and sleep-related characteristics. A total of 11 colleges and universities were surveyed from May 30 to June 17, 2021, by convenience sampling. A total of 1,240 participants provided usable data regarding sociodemographic information, Sleep Inertia Questionnaire, and sleep-related characteristics via an online platform. Latent profile analysis was utilised to identify profiles of SI. Multinomial logistic regression was further performed to examine the predisposing factors of profiles of SI. Four profiles of SI were identified: (1) "Low SI", 20%; (2) "Mild SI", 31%; (3) "Moderate SI", 33%; and (4) "Severe SI", 16%. Compared to a Low SI profile, younger, individuals with an evening chronotype, and individuals who had <6 h sleep/night, experienced poor sleep quality, and moderate-to-severe sleep disturbance were at increased risk of experiencing severe SI. Individuals with more languid types tended to show more severe SI, while individuals reporting greater flexibility experienced less SI. This study is the first effort to examine the profiles of subjective SI using latent profile analysis and identified four profiles of SI in the general population. This effort may contribute to a greater understanding of SI, including the development of a screening tool and interventions to reduce SI.

The effects of Danggui-Shaoyao-San on neuronal degeneration and amyloidosis in mouse and its molecular mechanism for the treatment of Alzheimer's disease.

The abnormal deposition of the extracellular amyloid-ß peptide is the typical pathological hallmark of Alzheimer's disease. Strategies to reduce the amyloid-ß deposition effectively alleviate the neuronal degeneration and cognitive deficits of Alzheimer's disease. Danggui-Shaoyao-San has been considered a useful therapeutic agent known for the treatment of Alzheimer's disease. However, the mechanism of Danggui-Shaoyao-San for the treatment of Alzheimer's disease remains unclear. We investigated Danggui-Shaoyao-San's effect on amyloidosis and neuronal degeneration in an APP/PS1 mouse model. We found Danggui-Shaoyao-San alleviated the cognitive deficits in APP/PS1 mice. Additionally, Danggui-Shaoyao-San ameliorated the neuronal degeneration in these mice. Danggui-Shaoyao-San reduced the amyloidosis and amyloid-ß1-42 deposition in APP/PS1 mouse brain and down-regulated the receptor for advanced glycation end products, and up-regulated the level of low-density lipoprotein receptor-related protein-1. However, the protein expression of the ß-amyloid precursor protein, ß-Secretase and presenilin-1 (PS1) in the amyloid-ß production pathway, and the expression of neprilysin and insulin-degrading enzyme in the amyloid-ß degradation pathway were not altered. Our findings collectively suggest that Danggui-Shaoyao-San could ameliorate the amyloidosis and neuronal degeneration of Alzheimer's disease, which may be associated with its up-regulation lipoprotein receptor-related protein-1 and down-regulation of the receptor for advanced glycation end products.

ASlive: a database for alternative splicing atlas in livestock animals.

BACKGROUND: Alternative splicing is an important biological process whose precision must be tightly regulated during growth and development. Although there are species, disease (e.g. cancers), or study specific databases available in many organisms, no database exists in livestock animals specifically tailored for alternative splicing. DESCRIPTION: We present in this study the development and implementation of a database for alternative splicing atlas in livestock animals (ASlive.org). Using publicly available RNASeq data sets across many tissues, cell types, and biological conditions totaling 28.6 T bases, we built a database of alternative splicing events in five major livestock and poultry animal species (cattle, sheep, pigs, horses, and chickens). The database contains many types of information on alternative splicing events, including basic information such as genomic locations, genes, and event types, quantitative measurements of alternative splicing in the form of percent spliced in (PSI), overlap with known DNA variants, as well as orthologous events across different lineage groups. CONCLUSIONS: This database, the first of its kind in livestock animals, will provide a useful exploratory tool to assist functional annotation of animal genomes.

InsectBase: a resource for insect genomes and transcriptomes.

The genomes and transcriptomes of hundreds of insects have been sequenced. However, insect community lacks an integrated, up-to-date collection of insect gene data. Here, we introduce the first release of InsectBase, available online at http://www.insect-genome.com. The database encompasses 138 insect genomes, 116 insect transcriptomes, 61 insect gene sets, 36 gene families of 60 insects, 7544 miRNAs of 69 insects, 96,925 piRNAs of Drosophila melanogaster and Chilo suppressalis, 2439 lncRNA of Nilaparvata lugens, 22,536 pathways of 78 insects, 678,881 untranslated regions (UTR) of 84 insects and 160,905 coding sequences (CDS) of 70 insects. This release contains over 12 million sequences and provides search functionality, a BLAST server, GBrowse, insect pathway construction, a Facebook-like network for the insect community (iFacebook), and phylogenetic analysis of selected genes.

Prediction of piRNAs using transposon interaction and a support vector machine.

BACKGROUND: Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNA primarily expressed in germ cells that can silence transposons at the post-transcriptional level. Accurate prediction of piRNAs remains a significant challenge. RESULTS: We developed a program for piRNA annotation (Piano) using piRNA-transposon interaction information. We downloaded 13,848 Drosophila piRNAs and 261,500 Drosophila transposons. The piRNAs were aligned to transposons with a maximum of three mismatches. Then, piRNA-transposon interactions were predicted by RNAplex. Triplet elements combining structure and sequence information were extracted from piRNA-transposon matching/pairing duplexes. A support vector machine (SVM) was used on these triplet elements to classify real and pseudo piRNAs, achieving 95.3 ± 0.33% accuracy and 96.0 ± 0.5% sensitivity. The SVM classifier can be used to correctly predict human, mouse and rat piRNAs, with overall accuracy of 90.6%. We used Piano to predict piRNAs for the rice stem borer, Chilo suppressalis, an important rice insect pest that causes huge yield loss. As a result, 82,639 piRNAs were predicted in C. suppressalis. CONCLUSIONS: Piano demonstrates excellent piRNA prediction performance by using both structure and sequence features of transposon-piRNAs interactions. Piano is freely available to the academic community at http://ento.njau.edu.cn/Piano.html .

OMIGA: Optimized Maker-Based Insect Genome Annotation.

Insects are one of the largest classes of animals on Earth and constitute more than half of all living species. The i5k initiative has begun sequencing of more than 5,000 insect genomes, which should greatly help in exploring insect resource and pest control. Insect genome annotation remains challenging because many insects have high levels of heterozygosity. To improve the quality of insect genome annotation, we developed a pipeline, named Optimized Maker-Based Insect Genome Annotation (OMIGA), to predict protein-coding genes from insect genomes. We first mapped RNA-Seq reads to genomic scaffolds to determine transcribed regions using Bowtie, and the putative transcripts were assembled using Cufflink. We then selected highly reliable transcripts with intact coding sequences to train de novo gene prediction software, including Augustus. The re-trained software was used to predict genes from insect genomes. Exonerate was used to refine gene structure and to determine near exact exon/intron boundary in the genome. Finally, we used the software Maker to integrate data from RNA-Seq, de novo gene prediction, and protein alignment to produce an official gene set. The OMIGA pipeline was used to annotate the draft genome of an important insect pest, Chilo suppressalis, yielding 12,548 genes. Different strategies were compared, which demonstrated that OMIGA had the best performance. In summary, we present a comprehensive pipeline for identifying genes in insect genomes that can be widely used to improve the annotation quality in insects. OMIGA is provided at http://ento.njau.edu.cn/omiga.html .

Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease.

Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting in insufficient sleep. It is often caused by sleep disorders, work demands (e.g., night shifts), and study pressure. Sleep deprivation promotes Aß deposition and tau hyperphosphorylation, which is a risk factor for the pathogenesis and progression of Alzheimer's disease (AD). Recent research has demonstrated the potential involvement of sleep deprivation in both the pathogenesis and progression of AD through glial cell activation, the glial lymphatic system, orexin system, circadian rhythm system, inflammation, and the gut microbiota. Thus, investigating the molecular mechanisms underlying the association between sleep deprivation and AD is crucial, which may contribute to the development of preventive and therapeutic strategies for AD. This review aims to analyze the impact of sleep deprivation on AD, exploring the underlying pathological mechanisms that link sleep deprivation to the initiation and progression of AD, which offers a theoretical foundation for the development of drugs aimed at preventing and treating AD.

Exosomes: A Cellular Communication Medium That Has Multiple Effects On Brain Diseases.

Exosomes, as membranous vesicles generated by multiple cell types and secreted to extracellular space, play a crucial role in a range of brain injury-related brain disorders by transporting diverse proteins, RNA, DNA fragments, and other functional substances. The nervous system's pathogenic mechanisms are complicated, involving pathological processes like as inflammation, apoptosis, oxidative stress, and autophagy, all of which result in blood-brain barrier damage, cognitive impairment, and even loss of normal motor function. Exosomes have been linked to the incidence and progression of brain disorders in recent research. As a result, a thorough knowledge of the interaction between exosomes and brain diseases may lead to the development of more effective therapeutic techniques that may be implemented in the clinic. The potential role of exosomes in brain diseases and the crosstalk between exosomes and other pathogenic processes were discussed in this paper. Simultaneously, we noted the delicate events in which exosomes as a media allow the brain to communicate with other tissues and organs in physiology and disease, and compiled a list of natural compounds that modulate exosomes, in order to further improve our understanding of exosomes and propose new ideas for treating brain disorders.

Combination treatment of Danggui Buxue Decoction and endothelial progenitor cells can enhance angiogenesis in rats with focal cerebral ischemia and hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD) is a classic prescription of traditional Chinese medicine that is mainly used for treating clinical anemia for more than 800 years. This prescription has been utilized for nourishing "Qi" and enriching "Blood" for women suffering from menopausal symptoms. Meanwhile, DBD has the role of improving angiogenesis and promoting the neuroprotective functions. Bone marrow-derived endothelial progenitor cells (EPCs) was suboptimal to treat the focal cerebral ischemia (FCI). Thus, it's may be a novel strategy of DBD combined with EPCs transplantation for the FCI. AIM OF THE STUDY: To investigate the mechanistic effects of DBD in combination with EPCs transplantation to improve behavioral function of the FCI and hyperlipidemia. MATERIALS AND METHODS: We used rats with hyperlipidemia to develop a FCI model using photo-thrombosis, and treated the DBD in combination with EPCs transplantation. We adopted the Modified Neurological Severity Score to evaluate the neurological deficit, undertook the 2,3,5-triphenyltetrazolium chloride staining to calculate the total infarct volume. We carried out the RT-qPCR, Immunohistochemical analyses, TUNEL, ELISA, and Western blotting to measure the gene and protein levels which related to anti-apoptosis mechanisms and angiogenesis. RESULTS: Administration of DBD in combination with EPCs transplantation was found to improve behavioral function, reducing the infarct volume and decrease the level of total-cholesterole (TC) and low-density lipoprotein-cholesterol (LDL-C). Treatment of DBD plus EPCs increased the mRNA and protein expression of vascular endothelial growth factor A, fibroblastic growth factor-2, and angiopoietin-1 and decreased the apoptosis of endothelial cells by activating the phosphoinositide 3-kinase/protein kinase B/Bcl-xL/Bcl-2 associated death promoter (PI3K/Akt/BAD) pathway and promoting activation of the extracellular signal-regulated kinase (ERK) pathway, which induced angiogenesis directly. CONCLUSIONS: Our findings provided that DBD administration combined with EPCs transplantation promoted reconstruction of nervous function. This was achieved by enhancing expression of the growth factors related to anti-apoptosis mechanisms and angiogenesis thanks to regulation of the PI3K/Akt/BAD and ERK signaling pathways, and might be relate to the lowering of TC and LDL-C levels.

Changes in suicidal ideation and related influential factors in college students during the COVID-19 lockdown in China.

This study aims to investigate the patterns and predictors of suicidal ideation (SI) trajectories among college students during extended lockdowns in China. A three-wave survey was conducted during the outbreak period, remission period, and prevention period of COVID-19. Distinct patterns of SI trajectories were established by grouping respondents based on temporal changes in SI. Multivariate logistic regressions were performed to examine predictors for delay-occurrence and persistent SI. From a total of 35,516 college students included in the study, rates of SI increased significantly from T1 to T2 (7.3% v. 9.4%) and from T2 to T3 (9.4% v. 12.6%). Five SI trajectories were observed: resilient (80.5% of the sample), recovery (3.6%), relapsing/remitting (4.8%), persistent dysfunction (2.3%) and delayed dysfunction (8.7%). Further, junior-year undergraduates, postgraduates, only-child families, mental health history, confirmed cases in the community of residence, depressive symptoms, and negative coping strategies were significant predictors of distinct SI trajectories, whereas greater social support, more positive coping strategies, and better family functioning were associated with a lower probability of developing delayed or persistent dysfunction during the lockdown period. These findings suggest that continuous preventive and intervening measures for college students during COVID-19 lockdowns are of global importance, particularly among vulnerable groups who experience the most distress.

Longitudinal trajectories of insomnia symptoms among college students during the COVID-19 lockdown in China.

PURPOSE: This study aimed to examine the patterns and predictors of the trajectories of college students' insomnia symptoms across different stages of the COVID-19 pandemic. METHODS: A total of 35,516 college students completed three online surveys during the COVID-19 outbreak period (3-10 February 2020), initial remission period (24 March-3 April 2020), and effective control period (1-15 June 2020), respectively. These surveys measured the participants' socio-demographic and pandemic related factors, insomnia symptoms, mental health status, and psychosocial factors. Multivariate logistic regressions were used to examine predictors for trajectory membership. RESULTS: The prevalence of insomnia symptoms increases during home quarantine. Five insomnia symptoms trajectories were observed: resistance (82.8% of the sample), recovery (5.0%), delayed-dysfunction (5.8%), chronic-dysfunction (1.8%), and relapsing/remitting (4.6%). Female gender, residence location in urban, has history of sleep problems, smoking, alcohol use, community or village has confirmed COVID-19 cases, current poor mental health, higher negative coping were related to higher risk of developing insomnia symptoms in at least one time point, whereas better family function increased the possibility of recovery relative to chronic dysfunction. Lower social support and positive coping could also cause insomnia chronicity. CONCLUSION: Adolescents have different trajectories of insomnia symptoms during pandemic lockdown. Although most adolescents did not experience insomnia or recovered over time, some adolescents, especially those with the risk factors noted above, exhibit delayed or chronic symptoms. These findings could inform mental health professionals regarding how to provide individualized and appropriate intervention for college students after their return to school.

How to improve the long-term quality of life, insomnia, and depression of survivors 10 years after the Wenchuan earthquake? A network analysis.

BACKGROUND: Previous studies have found a negative effect of depression and insomnia on the psychological health domain of quality of life (QOL) among earthquake survivors. However, little is known about the symptom-to-symptom interactions among the above psychological outcomes. This study thus aimed to assess the interplay among the above three variables in survivors 10 years after the Wenchuan earthquake at the symptom level. METHODS: A total of 744 survivors completed the questionnaire at 10 years post-earthquake, reporting depressive symptoms, insomnia symptoms, and the psychological health domain of QOL. All network structures were estimated and compared using the network analysis approach in R version 4.1.1. RESULTS: Among the 744 survivors, 593 individuals did not have significant depressive and insomnia symptoms, while 151 individuals reported depressive and/or insomnia symptoms. "Little energy", "Suicidal ideation", and "Spirituality" were the key highest bridge symptoms in the three networks, respectively. Additionally, there were significant differences in network global strength, network structure, and individual edge weights between individuals with and without depression and/or insomnia. CONCLUSIONS: Intervention programs aimed at treating symptoms, such as exercise therapy, cognitive behavioural therapy, and spirituality education, may improve the QOL of survivors following an earthquake.

Using network analysis to explore the key bridge symptoms between posttraumatic stress symptoms and posttraumatic growth among survivors 10 years after the Wenchuan earthquake in China.

Despite previous research has illustrated there is high-coexistence between posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) in the aftermath of traumatic events, few studies have conceptualized the coexistence mechanism of the two psychological phenomena. Using the network analysis, this study aimed to identify the key bridge symptoms and compare sex differences between PTSD symptoms and PTG elements in survivors 10 years after the Wenchuan earthquake in China. A total of 744 survivors 10 years after the Wenchuan earthquake in China completed self-reported questionnaires on demographics, PTSD symptoms (4-item of Posttraumatic Stress Disorder Checklist), and PTG (10-item of Posttraumatic Growth Inventory). Network analysis was used to identify the network structure of PTSD symptoms and elements of PTG, along with bridge symptoms. Additionally, sex differences in the network structure were compared by the Network Comparison Test. Results revealed that the network of PTSD symptoms and elements of PTG was robust to stability and accuracy tests. The key bridge symptoms in the network were "Stronger religious faith", "Changed priorities", and "Easily startled". There were significant differences in network global strength across sex, and network structure across the severity of property loss other than house damage. Future interventions targeting the three key bridge symptoms are expected to relieve the severity of PTSD and promote growth following exposure to traumatic events.

Network structure of insomnia and depressive symptoms among shift workers in China.

A bidirectional relationship between insomnia and depression has been observed. However, few studies have used network analysis to explore the interaction patterns in that association at the symptom level. This study aimed to estimate network structures of insomnia and depressive symptoms among shift workers, as well as to compare the differences in network properties between individuals without and with insomnia symptoms and/or at risk of depression. A total of 1883 shift workers were included in our study. Insomnia symptoms were evaluated by three items based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, and depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale. Network analyses were used for the statistical analysis. "Difficulty initiating sleep", "Hard to get started", and "Depressed mood" with higher expected influence (EI) values were identified as the most central symptoms within the insomnia-depressive networks among shift workers. The significant differences between individuals without and with insomnia symptoms and/or at risk of depression were observed in symptoms of "Difficulty initiating sleep" and "Hard to get started". "Depressed mood", "Difficulty initiating sleep", or "Hard to get started" were the most key symptoms that trigger and sustain the structure of insomnia and depressive symptom among shift workers. Hence, timely intervention for the above three symptoms in future research or clinical practice (e.g., cognitive behavioral therapy for insomnia) may be crucial in alleviating insomnia and depressive symptoms among shift workers.

Anti-depressive effects of Jiao-Tai-Wan on CORT-induced depression in mice by inhibiting inflammation and microglia activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-Tai-Wan (JTW) is a very famous traditional Chinese medicine formula for the treatment of psychiatric disorders, especially in anxiety, insomnia and depression. However, its molecular mechanism of treatment remains indistinct. AIM OF THE STUDY: We aimed to reveal the action mechanism of JTW on anti-depression via inhibiting microglia activation and pro-inflammatory response both in vivo and in vitro. MATERIAL AND METHODS: The corticosterone (CORT)-induced depression mouse model was used to evaluate the therapeutic efficacy of JTW. Behavioral tests (open field, elevated plus maze, tail suspension and forced swim test) were conducted to evaluate the effect of JTW on depressive-like behaviors. The levels of inflammatory factors and the concentration of neurotransmitters were detected by RT-qPCR or ELISA assays. Then three hippocampal tissue samples per group (Control, CORT, and JTW group) were sent for RNA sequencing (RNA-seq). Transcriptomics data analysis was used to screen the key potential therapeutic targets and signaling pathways of JTW. Based on 8 bioactive species of JTW by our previous study using High-performance liquid chromatography (HPLC) analysis, molecular docking analyses were used to predict the interaction of JTW-derived compounds and depression targets. Finally, the results of transcriptome and molecular docking analyses were combined to verify the targets, key pathways, and efficacy of JTW treatment in vivo and vitro. RESULTS: JTW ameliorated CORT-induced depressive-like behaviors, neuronal damage and enhanced the levels of monoamine neurotransmitters in the serum of mice. JTW also inhibited CORT-induced inflammatory activation of microglia and decreased the serum levels of interleukin- 6(IL-6) and interleukin- 1ß (IL-1ß) in vivo. Transcriptomic data analysis showed there were 10 key driver analysis (KDA) genes with the strongest correlation which JTW regulated in depression mice. Molecular docking analysis displayed bioactive compound Magnoflorine had the strongest binding force to the key gene colony-stimulating factor 1 receptor (CSF1R), which is the signaling microglia dependent upon for their survival. Meanwhile, CSF1R staining showed it was consistent with inflammatory activation of microglia. Our vitro experiment also showed JTW and CSF1R inhibitor significantly reduced lipopolysaccharide (LPS)/interferon-gamma (IFNÉ£)-induced inflammatory activation response in macrophage cells. CONCLUSIONS: Our study suggests that JTW might ameliorate CORT-induced neuronal damage in depression mice by inhibiting CSF1R mediated microglia activation and pro-inflammatory response.

Effect of Probenecid on Endothelial Cell Growth Rate and Retinal Angiogenesis in an Oxygen-Induced Retinopathy Model.

Objectives: Probenecid is an anion transport inhibitor, which, according to the connectivity map (CMap; a biological application database), interferes with hypoxia-induced gene expression changes in retinal vascular endothelial cells (ECs). Here, we investigated the influence of probenecid on retinal EC cytotoxicity and retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model. Methods: The retinal EC growth rate in the presence of hypoxia-mimicking concentrations of cobalt chloride (CoCl2) was determined using the thiazolyl blue tetrazolium bromide (MTT) assay and proliferating cell nuclear antigen (PCNA) expression. In OIR rats, probenecid was administered by intraperitoneal injection (i.p.) from postnatal day (P) 1 to P7. The concentrations of vitreous humor vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and placental growth factor (PlGF) were determined by using the ELISA kit at P21. The amount of newly formed vascular lumen was evaluated by histopathological examination. Retinopathy and neovascularization were assessed by scoring isolectin B4 fluorescein-stained retinal flat mounts. Western blots for liver tissue HIF-1α and hepcidin (HAMP) were performed. Results: In vitro, probenecid led to the recession of the hypoxia-induced EC growth rate. In vivo, compared to the OIR retina, the upregulation of VEGF, HIF-1α, and PlGF in phase II retinopathy of prematurity (ROP) was inhibited by probenecid administration. Moreover, probenecid ameliorated neovascularization and resulted in significantly reduced relative leakage fluorescence signal intensity in fluorescein-stained retinal flat mounts (p < 0.05). Probenecid alleviated the liver overactivation of HAMP and downregulation of HIF-1α in OIR rats. Conclusions: This is the first demonstration that implies that probenecid might be a protective compound against retinal angiogenesis in OIR. These changes are accompanied with decreased hyperoxia-mediated hepcidin overproduction. Although the relevance of the results to ROP needs further research, these findings may help establish potential pharmacological targets based on the CMap database.

The Effect of STAT3 Signal Pathway Activation on Retinopathy of Prematurity.

Objective: To investigate the mechanism of activation of the signal transducer and activator of transcription 3 (STAT3) signal pathway in the process of retinopathy of prematurity (ROP). Methods: Sixty newborn Sprague-Dawley (SD) rats were randomly separated into the hyperoxia and air control groups (n = 30/in each group). The serum hepcidin level on 21 d was measured using the enzyme-linked immunosorbent assay (ELISA). The expression of HAMP and STAT3 protein in the liver was determined using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Retinal neovasculature was evaluated by hematoxylin and eosin (HE) stain and fluorescein lectin. The retinal endothelial cells were treated with 250 µmol/L cobalt chloride for 72 h and added S3I-201. The STAT3 level was determined by western blotting. Results: The expression of STAT3 protein increased significantly after hyperoxia stimulation. The expression of HAMP mRNA in the hyperoxia group was significantly higher than that of the control group. The proliferation of retinal cells was inhibited, and the expression of STAT3 was increased. No significant difference was noted in vascular endothelial growth factor (VEGF) mRNA. The expression of STAT3 and VEGF mRNA was significantly reduced. Conclusion: The activation of the STAT3 signal pathway increased hepcidin expression, contributing to the pathogenesis of ROP. S3I-201 inhibited the expression of STAT3 and VEGF mRNA levels. This information provides potential novel therapeutic approach to the prevention and treatment of ROP.

Baicalin Inhibits Ferroptosis in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. To date, the exact etiology of ICH-induced brain injury is still unclear. Moreover, there is no effective treatment to delay or prevent disease progression currently. Increasing evidence suggests that ferroptosis plays a dominant role in the pathogenesis of ICH injury. Baicalin is a main active ingredient of Chinese herbal medicine Scutellaria baicalensis. It has been reported to exhibit neuroprotective effects against ICH-induced brain injury as well as reduce iron deposition in multiple tissues. Therefore, in this study, we focused on the protective mechanisms of baicalin against ferroptosis caused by ICH using a hemin-induced in vitro model and a Type IV collagenase-induced in vivo model. Our results revealed that baicalin enhanced cell viability and suppressed ferroptosis in rat pheochromocytoma PC12 cells treated with hemin, erastin and RSL3. Importantly, baicalin showed anti-ferroptosis effect on primary cortical neurons (PCN). Furthermore, baicalin alleviated motor deficits and brain injury in ICH model mice through inhibiting ferroptosis. Additionally, baicalin existed no obvious toxicity towards the liver and kidney of mice. Evidently, ferroptosis is a key pathological feature of ICH and baicalin can prevent the development of ferroptosis in ICH. As such, baicalin is a potential therapeutic drug for ICH treatment.