bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish
Authors: Kawabe Momoko , Nishida Takumi , Horita Chihoko , Ikeda Asami , Takahashi Ryuji , Inui Akio , Shiozaki Kazuhiro 
Published: August 2022

Sociability is an essential component of the linkage structure in human and other vertebrate communication. Low sociability is defined as a poor social approach, including social withdrawal and apathy, and is implicated in a variety of psychiatric disorders. Ninjinyoeito (NYT), a traditional Japanese herbal medicine, has been used in the medical field. This study aimed to determine the effect of NYT on low sociality in NPY-KO zebrafish. NPY-KO zebrafish were fed a 3% NYT-supplemented diet for 4 days and subjected to behavioral tests. In the mirror test, NPY-KO zebrafish fed a control diet showed avoidance behavior toward their mirror counterparts. In contrast, the treatment of NPY-KO zebrafish with NYT significantly increased their interaction with their counterparts in the mirror. In addition, a 3-chambers test was conducted to confirm the effect of NYT on the low sociality of NPY-KO zebrafish. NPY-KO zebrafish fed the control diet showed less interaction with fish chambers, while NYT treatment increased the interaction. Phosphorylation of ERK, a marker of neuronal activity, was significantly reduced in the whole brain of NYT-fed NPY-KO zebrafish, compared to the control diet. NYT treatment significantly suppressed hypothalamic-pituitary-adrenal-related genes (gr, pomc, and crh) and sympathetic-adrenal-medullary-related genes (th1, th2, and cck) in NPY-KO zebrafish. NYT administration significantly reduced mRNA levels of gad1b compared to the control diet, suggesting the involvement of GABAergic neurons in NYT-induced improvement of low sociability. Furthermore, the expression of CREB was suppressed when NPY-KO zebrafish were fed NYT. Next, we attempted to identify the effective herb responsible for the NYT-induced improvement of low sociability. NPY-KO zebrafish were fed an experimental diet containing the target herb for 4 days, and its effect on sociability was evaluated using the 3-chambers test. Results showed that Cinnamon Bark and Polygala Root treatments significantly increased time spent in the fish tank area compared to the control diet, while the other 10 herbs did not. We confirmed that these two herbs suppressed the activity of HPA-, SAM-, and GABAergic neurons, as well as NYT-treated zebrafish, accompanied by downregulation of CREB signaling. This study suggests the potential use of NYT as a drug for sociability disorders.
Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling
Authors: Zhang Jing , Cheng Yun-Jiu , Luo Chang-Jun , Yu Jia 
Published: August 2022

Background: Ectopic activation of renin-angiotensin-system contributes to cardiovascular and renal diseases. (Pro)renin receptor (PRR) binds to renin and prorenin, participating in the progression of nephrology. However, whether PRR could be considered as a therapeutic target for cardiac remodeling and heart failure remains unknown.Materials and methods: Transverse aortic constriction (TAC) surgery was performed to establish a mouse model of chronic pressure overload-induced cardiac remodeling. Neonatal rat cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were isolated and stimulated by Angiotensin II (Ang II). PRR decoy inhibitor PRO20 was synthesized and used to evaluate its effect on cardiac remodeling.Results: Soluble PRR and PRR were significantly upregulated in TAC-induced cardiac remodeling and Ang II-treated CMs and CFs. Results of In vivo experiments showed that suppression of PRR by PRO20 significantly retarded cardiac remodeling and heart failure indicated by morphological and echocardiographic analyses. In vitro experiments, PRO20 inhibited CM hypertrophy, and also alleviated CF activation, proliferation and extracellular matrix synthesis. Mechanically, PRO20 enhanced intracellular cAMP levels, but not affected cGMP levels in CMs and CFs. Moreover, treatment of PRO20 in CFs markedly attenuated the production of reactive oxygen species and phosphorylation of IRE1 and PERK, two well-identified markers of endoplasmic reticulum (ER) stress. Accordingly, administration of PRO20 reversed ER stressor thapsigargin-induced CM hypertrophy and CF activation/migration.Conclusion: Taken together, these findings suggest that inhibition of PRR by PRO20 attenuates cardiac remodeling through increasing cAMP levels and reducing ER stress in both CMs and CFs.
Hesperidin promotes gastric motility in rats with functional dyspepsia by regulating Drp1-mediated ICC mitophagy
Authors: Jia Qingling , Li Li , Wang Xiangxiang , Wang Yujiao , Jiang Kailin , Yang Keming , Cong Jun , Cai Gan , Ling Jianghong 
Published: August 2022

Hesperidin is one of the main active ingredients of Citrus aurantiumL. (Rutaceae) and tangerine peel, which have anti-inflammatory and antioxidant effects. In previous study, we found that gastric motility disorder in functional dyspepsia (FD) rats accompanied by excessive autophagy/mitochondrial swelling and even vacuolization in the interstitial cells of cajal (ICC), but the exact mechanism has not yet been investigated. Therefore, we used different doses of hesperidin (50 mg/kg, 100 mg/kg, and 200 mg/kg) to intervene in FD rats, and found that medium doses of hesperidin (100 mg/kg) significantly increased gastric motility in FD rats. Subsequently, FD rats were randomly divided into control group, model group, mdivi-1 group, mdivi-1+hesperidin group and hesperidin group, and mitochondrial division inhibitor (mdivi-1) was injected intraperitoneally to further investigate whether hesperidin could regulate dynamin-related protein 1 (Drp1)-mediated mitophagy in ICC to improve mitochondrial damage. The results showed that compared with the model group, the serum malondialdehyde (MDA) level decreased and the superoxide dismutase (SOD) level increased in the mdivi-1 and hesperidin groups (p &lt; 0.001). Transmission electron microscopy (TEM) observed that the mitochondrial nuclear membrane was intact in gastric tissues with a clear internal cristae pattern, and autophagy lysosomes were rare. The co-localization expression of microtubule associated protein 1 light chain 3 (LC3) and voltage dependent anion channel 1 (VDAC1), Drp1 and translocase of the outer mitochondrial membrane 20 (Tom20) was significantly decreased (p &lt; 0.001), the protein expression of mitochondrial Drp1, Beclin1 and LC3 were significantly decreased (p &lt; 0.001), the protein expression of mitochondrial P62 and ckit in gastric tissue were significantly increased (p &lt; 0.05, p &lt; 0.001). The above situation was improved more significantly by the synergistic intervention of mdivi-1 and hesperidin. Therefore, hesperidin can improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp1-mediated ICC mitophagy.
Up-and-coming anti-epileptic effect of aloesone in Aloe vera: Evidenced by integrating network pharmacological analysis, in vitro, and in vivo models
Authors: Wang Yan , Li Chang , Xiong Zhongyv , Chen Niangen , Wang Xuesong , Xu Junyv , Wang Yuemei , Liu Longfeng , Wu Hang , Huang Caihui , Huang Aiqin , Tan Jiajia , Li Youbin , Li Qifu 
Published: August 2022

Background:Aloe vera is a medically valuable plant with anti-epileptic activity; however, its mechanism of action remains unknown. In this study, network pharmacological, in vitro, and in vivo experiments were carried out to explore the potential anti-epileptic components and targets of Aloe vera.Methods: The main active components of Aloe vera were identified by searching the Traditional Chinese Medicine System Pharmacology database. Targets of Aloe vera were predicted using SwissTargetPrediction, whereas information about the epilepsy disease targets was obtained from Gene Cards. The protein–protein interaction network and core targets were screened according to the topological structure and CytoNCA plugin. The glutamate-induced HT22 cell line and pentylenetetrazol-induced seizure rats were used to confirm the effect of aloesone by detecting reactive oxygen species (ROS) and apoptosis, and predicting the targets.Results: A total of 14 core active components were selected based on the screening criteria of oral bioavailability ≥30% and drug-likeness ≥ 0.10. Four compounds, namely linoleic acid, aloesone, isoeleutherol glucosiden qt, and anthranol, demonstrated the potential ability of crossing the blood-brain barrier. A total of 153 targets associated with epilepsy were predicted for the four compounds. Moreover, after network analysis with CytoNCA, 10 targets, namely, MAPK1, SRC, MARK3, EGFR, ESR1, PTGS2, PTPN11, JAK2, PPKCA, and FYN, were selected as the core genes, and SRC, which has been predicted to be the target of aloesone and anthranol, exhibited the highest subgraph centrality value. In vitro experiments confirmed that aloesone treatment significantly inhibited the glutamate-induced neuronal injury by reducing the intracellular ROS content and the early phase of apoptosis. Additionally, treatment with 50 mg/kg aloesone resulted in anti-seizure effects by reducing the seizure score and prolonging the latent period in acute and chronic rats. Furthermore, aloesone treatment increased the phosphorylation of c-SRC at Y418 and reduced the phosphorylation at Y529, simultaneously activating c-SRC.Conclusion: Integrating network pharmacology with in vitro and in vivo experiments demonstrated that aloesone, which inhibited seizure by activating c-SRC, is a potential anti-seizure compound present in Aloe vera.
Preclinical safety evaluation of Macleaya Cordata extract: A re-assessment of general toxicity and genotoxicity properties in rodents
Authors: Dong Zhen , Tang Shu-Sheng , Ma Xiao-Lan , Li Chang-Hong , Tang Zhao-Shan , Yang Zi-Hui , Zeng Jian-Guo 
Published: August 2022

Macleaya cordata extract (MCE) is widely used for its diverse pharmacological actions and beneficial effects on farm animals. Modern pharmacological studies have shown that it has anti-inflammatory, anti-cancer, and anti-bacterial activities, and is gradually becoming a long-term additive veterinary drug used to improve animal intestinal health and growth performance. Although some evidence points to the DNA mutagenic potential of sanguinarine (SAN), a major component of MCE, there is a lack of sufficient basic toxicological information on the oral route, posing a potential safety risk for human consumption of food of animal origin. In this study, we assessed the acute oral toxicity, repeated 90-day oral toxicity and 180-day chronic toxicity of MCE in rats and mice and re-evaluated the genotoxicity of MCE using a standard combined in vivo and ex vivo assay. In the oral acute toxicity test, the LD50 for MCE in rats and mice was 1,564.55 mg/kg (95% confidence interval 1,386.97–1,764.95 mg/kg) and 1,024.33 mg/kg (95% confidence interval 964.27–1,087.30 mg/kg), respectively. The dose range tested had no significant effect on hematology, clinical chemistry, and histopathological findings in rodents in the long-term toxicity assessment. The results of the bacterial reverse mutation, sperm abnormality and micronucleus test showed negative results and lack of mutagenicity and teratogenicity; the results of the rat teratogenicity test showed no significant reproductive or embryotoxicity. The results indicate that MCE was safe in the dose range tested in this preclinical safety assessment. This study provides data to support the further development of maximum residue limits (MRLs) for MCE.
miR-3064-5p and miR-4745-5p affect heparin sensitivity in patients undergoing cardiac surgery by regulating AT-III and factor X mRNA levels
Authors: Ma Hai-Ping , Fu Min , Masula Maisitanguli , Xing Chang-Shuang , Zhou Qiang , Tan Jing-Tong , Wang Jiang 
Published: August 2022

Subject: Perioperative regulation of coagulation function through heparin in patients undergoing cardiac surgery with cardiopulmonary bypass is an important part of performing cardiac surgery, and postoperative bleeding due to abnormal coagulation function caused by differences in heparin sensitivity in different individuals is an independent risk factor for postoperative complications and death.Method: Using an online database, 10 miRNAs interacting with AT-III and FX genes were predicted. Patients were divided into three groups according to the difference in activated clotting time (ACT) after the first dose of heparin (2.5 mg kg−1): group A: hyposensitive group (ACT &lt; 480 s); group B: sensitive group (480 s ≤ ACT ≤ 760 s); and group C: hypersensitive group (ACT &gt; 760 s). Perioperative and 24 h postoperative blood loss and other clinical data of patients in the three groups were recorded. Blood samples were collected before surgery, and RT-PCR was used to detect the levels of AT-III and FX gene mRNA and the levels of predicted 10 miRNAs.Result: Heparin sensitivity was positively correlated with AT-III mRNA levels and negatively correlated with FX gene mRNA levels in the three groups, and the blood loss in group B was significantly lower than that in groups A and C, which was statistically significant (p &lt; 0.05). miR-3064-5p and miR-4745-5p expression levels were significantly different among group A, group B, and group C (p &lt; 0.05) and were closely correlated with AT-III and FX gene mRNA expression levels, respectively.Conclusion: Differences in heparin sensitivity in patients undergoing cardiac surgery were associated with the mRNA expression of AT-III and FX genes, and the expression levels of miR-3064-5p and miR-4745-5p were found to be closely related to the AT-III and FX gene mRNA, respectively, indicating that miR-3064-5p and miR-4745-5p affect the differences in heparin sensitivity among different individuals by regulating the mRNA expression levels of AT-III and FX genes.Clinical Trial Registration:http://www.chictr.org.cn/abouten.aspx, identifier registration number: ChiCTR-2100047348
Iron dyshomeostasis and time-course changes in iron-uptake systems and ferritin level in relation to pro-inflammatory microglia polarization in sepsis-induced encephalopathy
Authors: Sharawy Nivin , Imam Ahmad Abdel-Aliem , Aboulhoda Basma Emad , Khalifa Mohamed Mansour , Morcos George N. B. , Abd Algaleel Waleed Ahmed , Moustafa Passant E. , Abdelbaset Marwan A. , Shoukry Tarek 
Published: August 2022

Encephalopathy is a frequent and lethal consequence of sepsis. Recently, a growing body of evidence has provided important insights into the role of iron dyshomeostasis in the context of inflammation. The molecular mechanisms underlying iron dyshomeostasis and its relationship with macrophage phenotypes are largely unknown. Here, we aimed to characterize the changes in iron-transporter and storage proteins and the microglia phenotype that occur during the course of sepsis, as well as their relationship with sepsis-induced encephalopathy. We used a cecal ligation and puncture (CLP) murine model that closely resembles sepsis-induced encephalopathy. Rats were subjected to CLP or sham laparotomy, then were neurologically assessed at 6 h, 24 h, and 3 days after sepsis induction. The serum and brain were collected for subsequent biochemical, histological, and immunohistochemical assessment. Here, an iron excess was observed at time points that followed the pro-inflammatory macrophage polarization in CLP-induced encephalopathy. Our results revealed that the upregulation of non-transferrin-bound iron uptake (NTBI) and ferritin reduction appeared to be partially responsible for the excess free iron detected within the brain tissues. We further demonstrated that the microglia were shifted toward the pro-inflammatory phenotype, leading to persistent neuro-inflammation and neuronal damage after CLP. Taken together, these findings led us to conclude that sepsis increased the susceptibility of the brain to the iron burden via the upregulation of NTBI and the reduction of ferritin, which was concomitantly and correlatively associated with dominance of pro-inflammatory microglia and could explain the neurological dysfunction observed during sepsis.
Is exercise/physical activity effective at reducing symptoms of post-traumatic stress disorder in adults — A systematic review
Authors: Jadhakhan Ferozkhan , Lambert Nichola , Middlebrook Nicola , Evans David W. , Falla Deborah 
Published: August 2022

BackgroundExercise has been used to manage symptoms of post-traumatic stress disorder (PTSD). The effect of exercise on PTSD outcomes has been previously explored in several studies. However, it still remains unclear what type of exercise/physical activity, intensity and duration is most effective for reducing symptoms of PTSD. A systematic review was conducted to determine which forms of exercise or physical activity have the greatest effect on PTSD outcome scores including an evaluation of exercise frequency and volume.MethodsThe following electronic databases were systematically searched from January 1980 to June 2021: MEDLINE, PsycINFO, PubMed and Web of Science. Inclusion criteria were studies investigating adults aged 18 or over, reporting the effect of exercise and physical activities on PTSD symptom outcome scores. Two reviewers independently extracted information on study characteristics, exposure and outcomes. In total of 3,217 articles were screened and 23 full text articles further assessed, with 13 RCT's included in the review, covering seven exercise/physical activity interventions. The study protocol was registered prospectively with PROSPERO (CRD42021255131).ResultsThirteen studies from four countries involving a total of 531 patients were selected for inclusion. Individual forms of exercise/physical activity examined showed some effect on reducing PTSD symptoms but combined exercises (resistance training, aerobic, strength and yoga) administered over a 12 week period, three times a week for 30–60 min showed greater effects on PTSD symptoms.ConclusionThe limited evidence suggests that a combined exercise intervention has the best evidence for a having a beneficial effect on PTSD symptoms.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255131.
Efficacy of Smartphone Apps in Patients With Depressive Disorders: A Systematic Review
Authors: Hernández-Gómez Alba , Valdés-Florido María José , Lahera Guillermo , Andrade-González Nelson 
Published: August 2022

BackgroundDigital interventions have become an accessible format in clinical practice to provide better support for patients with mental disorders. However, the clinical efficacy in patients with depressive disorders is not well known. We aimed to determine the efficacy of smartphone applications (apps) in patients diagnosed with a depressive disorder.MethodAn electronic database search was performed of PubMed, PsycINFO, and Web of Science, to identify relevant articles up to June 12, 2021. Peer-reviewed articles were screened and selected based on predetermined inclusion and exclusion criteria.ResultsSeven articles met the inclusion criteria and therefore were selected for the systematic review, which included a total of 651 patients. The results were heterogeneous, essentially due to the different methodologies used in the selected studies.ConclusionsDigital smartphone-delivered interventions do not appear to reduce depressive symptomatology nor improve the quality of life in patients diagnosed with depressive disorders when compared to an active control group. Taking into account the inherent methodological difficulties and the variability among such studies, it is apparent that further research—with more methodologically refined clinical trials, including larger sample sizes—is needed.
Public stigma profile toward mental disorders across different university degrees in the University of Valencia (Spain)
Authors: Ruiz Juan C. , Fuentes-Durá Inmaculada , López-Gilberte Marta , Dasí Carmen , Pardo-García Cristina , Fuentes-Durán María C. , Pérez-González Francisco , Salmeron Ladislao , Soldevila-Matías Pau , Vila-Francés Joan , Balanza-Martínez Vicent 
Published: August 2022

BackgroundA large proportion of studies carried out in recent years in different populations have shown that stigma toward mental disorders is highly prevalent. In the present study we conducted a comprehensive assessment of stigma to describe and compare stigma toward mental disorders in students enrolled in five different university degrees.MethodsThree hundred and twenty-five students from the University of Valencia (Spain), attending the second term of their first-degree courses in the faculties of medicine, psychology, teaching, economics, and data science participated in this cross-sectional study. Stigma was measured using: the Reported and Intended Behavior Scale (RIBS), the Scale of Community Attitudes toward Mental Illness (CAMI), the Attribution Questionnaire (AQ-27), and the Knowledge about Mental Illness test (KMI).ResultsWe found different patterns of stigma according to gender, the fact of knowing or living with a person with mental disorders and the university degree studied. Overall, women show fewer stigmatizing attitudes than men but similar stereotypes and prejudice toward people with mental disorders. However, the pattern of results across degrees is more complex. Overall, students of medicine, psychology and teaching showed fewer stigmatizing attitudes than students of economics and data science but differences between degrees were more subtle in stereotypes and prejudice toward people with mental disorders.ConclusionOur study suggests the existence of different profiles of stigma in relation to mental disorders in university students. These profiles varied in relation with the degree being studied, gender and already knowing or living with a person with mental disorders.