bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Serum Regulator of Calcineurin 2 is Associated With an Increased Risk of Non-Alcoholic Fatty Liver Disease
Authors: Fang Xia , Wang Hongya , Tan Xiaozhen , Ye Ting , Xu Yong , Fan Jiahao 
Published: March 2022

Background: The promoting effect of the regulator of calcineurin 2 (RCAN2) in hepatic steatosis has been observed in animal studies. However, the association of RCAN2 with non-alcoholic fatty liver disease (NAFLD) in humans remains unclear. This study aimed to evaluate the expression of RCAN2 in the liver of mice with hepatic steatosis and in the serum of NAFLD patients and to explore the relationship between serum RCAN2 levels and NAFLD.Methods: The mRNA and protein expression of RCAN2 were detected by quantitative real-time PCR (qRT-PCR) and Western blot. NAFLD was diagnosed by abdominal ultrasonography. Circulating RCAN2 levels were measured by ELISA kits. The relationship between serum RCAN2 levels and NAFLD was assessed.Results: qRT-PCR and Western blot analysis showed that compared with the corresponding controls, the mRNA and protein expression of RCAN2 were significantly increased in the liver tissues of db/db and mice on a high-fat diet. Serum RCAN2 levels were markedly elevated in NAFLD patients compared with non-NAFLD subjects. Binary logistic regression analysis showed that serum RCAN2 levels were significantly associated with NAFLD. Receiver operation characteristic (ROC) curve analysis showed that serum RCAN2 might act as a predictive biomarker for NAFLD [area under the curve (AUC) = 0.663, 95% CI = 0.623–0.702], and the serum RCAN2/(AST/ALT) ratio displayed improved predictive accuracy (AUC = 0.816, 95% CI = 0.785–0.846).Conclusion: Elevated serum RCAN2 levels were associated with an increased risk of NAFLD. Serum RCAN2, especially the serum RCAN2/(AST/ALT) ratio, might be a candidate diagnostic marker for NAFLD.
Investigation of Antiparasitic Activity of Two Marine Natural Products, Estradiol Benzoate, and Octyl Gallate, on Toxoplasma gondii In Vitro
Authors: Lu Daiqiang , Zhang Nian-Zhang , Yao Yinning , Wang Tingting , Hua Qianqian , Zheng Xiaozi , Cong Wei , Tan Feng 
Published: March 2022

Toxoplasmosis, caused by Toxoplasma gondii, is a common disease worldwide and could be severe and even fatal in immunocompromised individuals and fetuses. Limitation in current available treatment options drives the need to develop novel therapeutics. This study assessed the anti-T. gondii potential of 103 marine natural products. A luminescence-based β-galactosidase activity assay was used to screen the marine natural products library. Afterward, those compounds that displayed over 70% parasite inhibition ratio were further chosen to assess their cytotoxicity. Compounds exhibiting low cytotoxicity (≥80% cell viability) were applied to evaluate the inhibition efficacy on discrete steps of the T. gondii lytic cycle, including invasion, intracellular growth, and egress abilities as well as the cell cycle. We found that both estradiol benzoate and octyl gallate caused &gt;70% inhibition of tachyzoite growth with IC50 values of 4.41 ± 0.94 and 5.66 ± 0.35 μM, respectively, and displayed low cytotoxicity with TD50 values of 34.11 ± 2.86 and 26.4 ± 0.98 μM, respectively. Despite their defects in inhibition of invasion and egress of tachyzoite, the two compounds markedly inhibited the tachyzoite intracellular replication. Flow cytometric analyses further suggested that the anti-T. gondii activity of estradiol benzoate, rather than octyl gallate, may be linked to halting cell cycle progression of tachyzoite from G1 to S phase. Taken together, these findings suggest that both estradiol benzoate and octyl gallate are potential inhibitors for anti-T. gondii infection and support the further exploration of marine natural products as a thinkable source of alternative and active agents against T. gondii.
The Enantiomer of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy
Authors: Ishikawa Makoto , Nakazawa Toru , Kunikata Hiroshi , Sato Kota , Yoshitomi Takeshi , Krishnan Kathiresan , Covey Douglas F. , Zorumski Charles F. , Izumi Yukitoshi 
Published: March 2022

In an ex vivo rat ocular hypertension (OHT) model, the neurosteroid allopregnanolone (AlloP) exerts neuroprotective effects via enhancement of both GABAA receptors and autophagy. We now examine whether its enantiomer (ent-AlloP), which is largely inactive at GABA receptors, offers similar neuroprotection in ex vivo and in vivo rat OHT models. Ex vivo rat retinal preparations were incubated in a hyperbaric condition (10 and 75 mmHg) for 24 h. An in vivo ocular hypertension (OHT) model was induced by intracameral injection of polystyrene microbeads. We examined pharmacological effects of AlloP, ent-AlloP, picrotoxin (a GABAA receptor antagonist), and 3-MA (an autophagy inhibitor) histologically and biochemically. We found that both AlloP and ent-AlloP have marked neuroprotective effects in the retina, but effects of the unnatural enantiomer are independent of GABAA receptors. Electron microscopic analyses show that pressure elevation significantly increased autophagosomes (APs) in the nerve fiber layer and addition of AlloP also increased APs and degenerative autophagic vacuoles (AVds). ent-AlloP markedly increased APs and AVds compared to AlloP. Examination of LC3B-II and SQSTM1 protein levels using immunoblotting revealed that AlloP increased LC3B-II, and ent-AlloP further enhanced LC3B-II and suppressed SQSTM1, indicating that autophagy is a major mechanism underlying neuroprotection by ent-AlloP. In an rat in vivo OHT model, single intravitreal ent-AlloP injection prevented apoptotic cell death of retinal ganglion cells similar to AlloP. However, even in this model, ent-AlloP was more effective in activating autophagy than AlloP. We conclude that ent-AlloP may be a prototype of potential therapeutic for treatment of glaucoma as an autophagy enhancer without affecting GABA receptors.
Notoginsenoside R1 Ameliorates Cardiac Lipotoxicity Through AMPK Signaling Pathway
Authors: Tian Xue , Chen Xu , Jiang Qianqian , Sun Qianbin , Liu Tiantian , Hong Yiqin , Zhang Yawen , Jiang Yanyan , Shao Mingyan , Yang Ran , Li Chun , Wang Qiyan , Wang Yong 
Published: March 2022

Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.
Anti-atrial Fibrillation Effects of Pulmonary Vein Isolation With or Without Ablation Gaps: A Computational Modeling Study
Authors: Jin Ze , Hwang Inseok , Lim Byounghyun , Kwon Oh-Seok , Park Je-Wook , Yu Hee-Tae , Kim Tae-Hoon , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam 
Published: March 2022

BackgroundAlthough pulmonary vein isolation (PVI) gaps contribute to recurrence after atrial fibrillation (AF) catheter ablation, the mechanism is unclear. We used realistic computational human AF modeling to explore the AF wave-dynamic changes of PVI with gaps (PVI-gaps).MethodsWe included 40 patients (80% male, 61.0 ± 9.8 years old, 92.5% persistent AF) who underwent AF catheter ablation to develop our realistic computational AF model. We compared the effects of a complete PVI (CPVI) and PVI-gap (2-mm × 4) on the AF wave-dynamics by evaluating the dominant frequency (DF), spatial change of DF, maximal slope of the action potential duration restitution curve (Smax), and AF defragmentation rate (termination or change to atrial tachycardia), and tested the effects of additional virtual interventions and flecainide on ongoing AF with PVI-gaps.ResultsCompared with the baseline AF, CPVIs significantly reduced extra-PV DFs (p &lt; 0.001), but PVI-gaps did not. COV-DFs were greater after CPVIs than PVI-gaps (p &lt; 0.001). Neither CPVIs nor PVI-gaps changed the mean Smax. CPVIs resulted in higher AF defragmentation rates (80%) than PVI-gaps (12.5%, p &lt; 0.001). In ongoing AF after PVI-gaps, the AF defragmentation rates after a wave-breaking gap ablation, extra-PV DF ablation, or flecainide were 60.0, 34.3, and 25.7%, respectively (p = 0.010).ConclusionCPVIs effectively reduced the DF, increased its spatial heterogeneity in extra-PV areas, and offered better anti-AF effects than extra-PV DF ablation or additional flecainide in PVI-gap conditions.
Assessment of Choroidal Vascularity and Choriocapillaris Blood Perfusion After Accommodation in Myopia, Emmetropia, and Hyperopia Groups Among Children
Authors: Chang Xuejiao , Li Mu , Lv Liang , Yan Xiaoqin , Liu Ying , Zhu Mengxia , Wang Junming , Wang Ping , Xiang Yan 
Published: March 2022

PurposeTo investigate choroidal vascularity (CV) and choriocapillaris blood perfusion before and after accommodation in myopia, emmetropia, and hyperopia groups among children.MethodsThis study included 39 myopic eyes from 22 subjects, 17 emmetropic eyes from 11 subjects, and 18 hyperopic eyes from 10 subjects. All subjects were children. Choroidal thickness (CT) and CV, including total choroidal area (TCA), luminal area (LA), and stromal area (SA) were measured using swept-source optical coherence tomography (SS-OCT). Choriocapillaris luminal area (CLA) was measured using SS-OCT-angiography before and after accommodation (near reading with an additional −3 diopter lens).ResultsFor baseline results, except horizontal CV (showing no significant differences between myopia and emmetropia groups), both horizontal and vertical CT and CV were significantly smaller in the myopia group than in the emmetropia or hyperopia groups. In terms of CLA, no significant differences were observed among the myopia, emmetropia, and hyperopia groups. In addition, only myopic eyes showed significant decreases in CT and CV, whereas most CT and CV of emmetropic and hyperopic eyes showed non-significant decreases after accommodation. Furthermore, accommodation induced no significant changes in CLA in the myopia, emmetropia, or hyperopia groups.ConclusionMyopia had thinner baseline choroid and lower baseline choroidal blood perfusion. Furthermore, myopic eyes were more prone to choroidal thinning and blood perfusion decreases after accommodation.
The Therapeutic Effect of Exogenous Melatonin on Depressive Symptoms: A Systematic Review and Meta-Analysis
Authors: Li Cancan , Ma Dandan , Li Min , Wei Tao , Zhao Xuan , Heng Yuanyuan , Ma Delong , Anto Enoch Odame , Zhang Yanbo , Niu Mingyun , Zhang Wangxin 
Published: March 2022

BackgroundDepression-related mortality and morbidity pose growing public health burdens worldwide. Although the therapeutic effect of exogenous melatonin on depression has been investigated, findings remain inconsistent. We conducted this systematic review and meta-analysis to clarify the effectiveness of melatonin in the treatment of depression, including primary and secondary depression symptoms.MethodsWe searched the online databases of PubMed, EMBASE, and the Cochrane Library for original studies published up to May 2021. We used STATA 14.0 software to synthesize the results of included studies. To evaluate the effectiveness of melatonin, we calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs) of depression scores between the melatonin and placebo groups.ResultsOur literature search returned 754 publications, among which 19 studies with 1,178 patients (715 women, 463 men; mean age: 56.77 years) met inclusion criteria. Melatonin dosages ranged from 2 to 25 mg per day; treatment durations were between 10 days and 3.5 years. Our synthesized results showed that melatonin was not found significantly beneficial for alleviating depressive symptoms (SMD = −0.17, 95% CI = [−0.38, 0.05]). Subgroup analysis demonstrated that the decrease in depression scores measured with the Beck Depression Inventory (BDI) was significant (SMD = −0.52, 95% CI = [−0.73, −0.31]).ConclusionsThere is very limited evidence for effects of melatonin on depression.
Risk Profiles of Korean Adolescents in Relations With Contextual Factors: Implications for Multi-Tiered Systems of Support
Authors: Kim Dongil , Lim Jin Hyung 
Published: March 2022

IntroductionAlthough prior studies have supported the effectiveness of Multi-Tiered Systems of Support (MTSS) on addressing social, emotional, behavioral, and academic challenges faced by youth at-risk, educators using MTSS often do not consider contextual factors which may also influence youth at-risk and the interventions targeting them. This study thus aimed to identify youth at-risk who should be referred to targeted instructions within MTSS by examining the risk profiles of Korean adolescents. Based on the identified risk profiles, we also tried to investigate the effect of contextual factors on deciding youth at-risk and confirm whether and/or what contextual factors should be considered when implementing targeted interventions for them.MethodTo accomplish the research goal, a latent profile analysis on risk factors of Korean adolescents was performed, using the first year data of “Korean Children and Youth Panel Study (KCYPS) 2018.”ResultsFour risk profiles were identified, using low academic motivation, low academic behavior, attention deficit, aggression, social withdrawal, and depression as indicators: the high risk, M-SEB (Moderate-social, emotional, &amp; behavioral) risk, M-ACA (Moderate-academic) risk, and low risk group. The covariates of this study, home and school environmental variables, worked as predictors of adolescents included in the high group.ConclusionThe results of this study suggest students in the high risk group (16.8%) should be given targeted instructions combining academic and SEB support within MTSS so as to prevent negative outcomes in the future among all adolescents. Those instructions need to be planned with consideration of contextual factors accompanied by teacher's careful understanding of social dynamics surrounding each student.
A “Good” Smoke? The Off-Label Use of Cannabidiol to Reduce Cannabis Use
Authors: Fortin Davide , Di Beo Vincent , Massin Sophie , Bisiou Yann , Carrieri Patrizia , Barré Tangui 
Published: March 2022

BackgroundAlthough cannabis use is common in France, it is still criminalized. Cannabidiol (CBD) products, including CBD-rich cannabis, are legally available. Although previous results suggested that CBD may have benefits for people with cannabis use disorder, there is a lack of data on cannabis users who use CBD to reduce their cannabis consumption. We aimed to identify (i) correlates of this motive, and (ii) factors associated with successful attempts to reduce cannabis use.MethodsA cross-sectional online survey among French-speaking CBD and cannabis users was conducted. Logistic regressions were performed to identify correlates of using CBD to reduce cannabis consumption and correlates of reporting a large reduction.ResultsEleven percent (n = 105) of our study sample reported they primarily used CBD to reduce cannabis consumption. Associated factors included smoking tobacco cigarettes (adjusted odds ratio (aOR) [95% confidence interval (CI)] 2.17 [1.3–3.62], p = 0.003) and drinking alcohol (aOR [95%CI] 1.8 [1.02–3.18], p = 0.042). Of these 105, 83% used CBD-rich cannabis to smoke, and 58.7% reported a large reduction in cannabis consumption. This large reduction was associated with non-daily cannabis use (aOR [95%CI] 7.14 [2.4–20.0], p &lt; 0.001) and daily CBD use (aOR [95%CI] 5.87 [2.09–16.47], p = 0.001). A reduction in cannabis withdrawal symptoms thanks to CBD use was the most-cited effect at play in self-observed cannabis reduction.ConclusionsCannabis use reduction is a reported motive for CBD use—especially CBD-rich cannabis to smoke—in France. More studies are needed to explore practices associated with this motive and to accurately assess CBD effectiveness.
Differential Effects of Aripiprazole and Amisulpride on Negative and Cognitive Symptoms in Patients With First-Episode Psychoses
Authors: Nielsen Mette Ødegaard , Kristensen Tina Dam , Borup Bojesen Kirsten , Glenthøj Birte Y. , Lemvigh Cecilie K. , Ebdrup Bjørn H. 
Published: March 2022

IntroductionAripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses.MethodsPsychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions.ResultsLongitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [F(1, 93) = 4.29, p = 0.041] and a significant effect of time [F(1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [t(47) = 4.1, p &lt; 0.001] and not observed in patients treated with amisulpride (p &gt; 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect.ConclusionPatients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions.
A Retrospective Study on the Eye-Related Quality of Life, Functional Vision, and Their Determinants Among Children Following Congenital and Developmental Cataracts Surgery and Its Impact on Their Families Using the PedEyeQ
Authors: Gu Siyi , Hu Yiwen , Zhao Yinying , Chen Lulu , Sun Weijie , Chang Pingjun , Wang Dandan , Zhao Yune 
Published: March 2022

ObjectivesTo evaluate the eye-related quality of life (ER-QOL), functional vision, and their determinants in children following congenital and developmental cataract surgery, as the impact on their families, using the Pediatric Eye Questionnaire (PedEyeQ).Materials and MethodsThis was a retrospective cross-sectional study involving 107 children (aged 0–11 years) with congenital and developmental cataracts who had undergone surgery, as well as 59 visually healthy controls (aged 0–11 years). One parent for each child completed either the Proxy 0–4 PedEyeQ, the Proxy 5–11 PedEyeQ, or the Parent PedEyeQ, depending on their child's age. Mann-Whitney U and Kruskal-Wallis tests were then conducted to compare the differences between groups and to analyze their determinants.ResultsPedEyeQ scores were found to be lower in postoperative children with congenital and developmental cataracts compared with the control group across all study domains. The PedEyeQ Proxy 0 to 4 years' greatest mean difference was 27 points worse in the Functional Vision domain (95% CI −34 to −19; p &lt; 0.001). We also found that the occurrence of nystagmus (p &lt; 0.005) and strabismus (p &lt; 0.005) were the major factors affecting participants' functional vision. The PedEyeQ Proxy 5 to 11 years' greatest mean difference was 23 points worse in this same domain (95% CI −30 to −15; p &lt; 0.001), with nystagmus (p &lt; 0.05) being the main determinant herein. Parent PedEyeQ 0 to 4 years' greatest difference was 46 points worse on the Worry about their Child's Eye Condition domain (95% CI −57 to −36; p &lt; 0.001). Similarly, parents of children with ophthalmologic abnormalities, including nystagmus (p &lt; 0.001) and strabismus (p &lt; 0.05), were significantly more worried about their children's eye condition. Parent PedEyeQ 5 to 11 years' greatest difference was also found to be 30 points worse on the Worry about their Child's Eye Condition domain (95% CI −43 to −17; p &lt; 0.005).ConclusionsChildren who have undergone congenital and developmental cataract surgery experience a lower quality of life and reduced functional vision. Their families are also significantly and adversely affected herein. Thus, more attention is needed on these groups, with more focused measures being administered to both children and their families.