bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-Specific Effects of Acute Ethanol Exposure on Locomotory Activity and Exploratory Behavior in Adult Zebrafish (Danio rerio)
Authors: Vossen Laura E. , Brunberg Ronja , Rådén Pontus , Winberg Svante , Roman Erika 
Published: June 2022

The zebrafish (Danio rerio) is an established model organism in pharmacology and biomedicine, including in research on alcohol use disorders and alcohol-related disease. In the past 2 decades, zebrafish has been used to study the complex effects of ethanol on the vertebrate brain and behavior in both acute, chronic and developmental exposure paradigms. Sex differences in the neurobehavioral response to ethanol are well documented for humans and rodents, yet no consensus has been reached for zebrafish. Here, we show for the first time that male zebrafish of the AB strain display more severe behavioral impairments than females for equal exposure concentrations. Adult zebrafish were immersed in 0, 1 or 2% (v/v) ethanol for 30 min, after which behavior was individually assessed in the zebrafish Multivariate Concentric Square Field™ (zMCSF) arena. Males exposed to 2% ethanol showed clear signs of sedation, including reduced activity, increased shelter seeking and reduced exploration of shallow zones. The 1% male group displayed effects in the same direction but of smaller magnitude; this group also explored the shallow areas less, but did not show a general reduction in activity nor an increase in shelter seeking. By contrast, 1 and 2% exposed females showed no alterations in explorative behavior. Females exposed to 2% ethanol did not display a general reduction in activity, rather activity gradually increased from hypoactivity to hyperactivity over the course of the test. This mixed stimulatory/depressant effect was only quantifiable when locomotory variables were analyzed over time and was not apparent from averages of the whole 30-min test, which may explain why previous studies failed to detect sex-specific effects on locomotion. Our results emphasize the importance of explicitly including sex and time as factors in pharmacological studies of zebrafish behavior. We hypothesize that the lower sensitivity of female zebrafish to ethanol may be explained by their greater body weight and associated larger distribution volume for ethanol, which may render lower brain ethanol concentrations in females.
Knowledge, Attitudes and Practice of Healthcare Providers, Healthcare Regulatory Practitioners and Patients Toward Biosimilars in China: Insights From a Nationwide Survey
Authors: Hu Yang , Song Zaiwei , Jiang Dan , Zhuo Lin , Cheng Yinchu , Zhao Rongsheng 
Published: June 2022

Objective: With increasing numbers of biosimilars entering the market or in the approval pipeline in China, understanding the current awareness and attitudes of biosimilars still remains the first step to promote uptake. This study aims to investigate the knowledge, attitudes and practices (KAP) of multiple stakeholders toward biosimilars, including healthcare providers (HCPs), healthcare regulatory practitioners and patients, and to provide practical information for future uptake of biosimilars in China.Methods: This nationwide cross-sectional online survey was conducted in mainland China. The questionnaire with a high level of reliability and validity was designed based on previous studies and clinical questions in the Clinical Practice Guideline for Clinical Application of Biosimilars. Logistic regression model was employed to identify possible impact factors, and Spearman’s rank correlation test was used to identify the correlation between knowledge and attitudes. Chi-squared test was used to compare the differences between different stakeholders.Results: Overall, 599 valid respondents were recruited, of whom 77.63%, 7.01% and 15.36% were HCPs, healthcare regulatory practitioners and patients, respectively. A total of 504 respondents who had heard of biosimilars were included in the KAP analysis. 76.70% of HCPs, 90.24% of healthcare regulatory practitioners and 50.98% of patients had good knowledge about the definition, while less familiarity with the development process and regulations on interchangeability and indication extrapolation was found in the former two groups. For attitudes toward biosimilars, an overall lack of positivity was shown, as only 18.20% HCPs, 14.63% healthcare regulatory practitioners and 23.53% patients were classified as having positive attitudes. More specifically, most respondents were positive about the influence of payment policy on the uptake of biosimilars, but they showed a neutral attitude toward the clinical medication and interchangeability of biosimilars. Efficacy, safety, immunogenicity, interchangeability and indication extrapolation are major concerns when utilizing biosimilars. Regarding practice, our study showed an inadequate utilization of biosimilars in China. Several further suggestions on the regulation of biosimilars were proposed by healthcare regulatory practitioners.Conclusions: There is still plenty of room for improvement of knowledge, attitudes and practice toward biosimilars among multiple stakeholders in China, which can be improved through high-quality real world evidence, educational programs and other effective measures directed towards barriers.
A Cyclic Disulfide Diastereomer From Bioactive Fraction of Bruguiera gymnorhiza Shows Anti–Pseudomonas aeruginosa Activity
Authors: Dahibhate Nilesh Lakshman , Shukla Sanjeev K. , Kumar Kundan 
Published: June 2022

Pseudomonas aeruginosa is an opportunistic pathogen that commonly causes hospital-acquired infection and is of great concern in immunocompromised patients. The quorum sensing (QS) mechanism of P. aeruginosa is well studied and known to be responsible for pathogenicity and virulence. The QS inhibitor derived from the natural product can be an important therapeutic agent for pathogen control. The present study reports the role of Bruguiera gymnorhiza purified fraction (BG138) in inhibiting virulence factor production, biofilm formation, quorum sensing molecules, and expression of QS-related genes of P. aeruginosa. Structural characterization of BG138 by high resolution mass spectrometry, Fourier transform infrared spectroscopy, 1D (1H and 13C NMR) and 2D NMR reveals that the fraction is a mixture of already known cyclic disulfide diastereomer, namely, brugierol and isobrugierol. The minimum inhibitory concentration (MIC) of BG138 against P. aeruginosa was 32 μg/ml. Biofilm formation was significantly reduced at sub-MIC concentrations of BG138. Scanning electron microscopy analysis reports the concentration-dependent biofilm inhibition and morphological changes of P. aeruginosa. Flow cytometry–based cell viability assay showed that P. aeruginosa cells exhibit increased propidium iodide uptake on treatment with 32 and 64 μg/ml of BG138. At sub-MIC concentrations, BG138 exhibited significant inhibition of virulence factors and reduced swimming and swarming motility of P. aeruginosa. Furthermore, the effect of BG138 on the expression of QS-related genes was investigated by qRT-PCR. Taken together, our study reports the isolation and structural characterization of bioactive fraction BG138 from B. gymnorhiza and its anti-biofilm, anti-virulence, anti-quorum sensing, and cell-damaging activities against P. aeruginosa.
Effects of Huolisu Oral Solution on Depression-Like Behavior in Rats: Neurotransmitter and HPA Axis
Authors: Xiao Min , Xie Kaiyong , Yuan Li , Wang Jun , Liu Xing , Chen Zhonghua 
Published: June 2022

Background: Depression is a common mental disorder, and its morbidity rate is expected to rank second among all mental disorders by 2020. Hence, traditional Chinese medicines gradually attract the attention of many researchers because of their various targets and low toxicity. Huolisu oral solution (HLS) is a Chinese medicine compound preparation, which is present in the Chinese Pharmacopoeia. It is used clinically mainly for the treatment of neurasthenia, perimenopausal syndrome, and insomnia, or depression associated with cerebrovascular disease. Despite the fact that HLS has been used as an antidepressant in clinics, the underlying mechanism is still an untouched domain. To provide a theoretical basis for the clinical application, a series of assessment methods, such as the tail suspension test (TST), forced swim test (FST), and locomotor activity test in mice and rat models of chronic unpredictable mild stress (CUMS), have been conducted in our study.Objective: The aim of the study was to explore the antidepressive effect and mechanism of HLS.Methods: CUMS was induced in rats to simulate a depression-like behavior. Neurotransmitters and hormones were detected by enzyme-link immunosorbent assay (ELISA). Pathomorphology examination of the hippocampus was obtained by using the TSView 7 image analysis system. The active ingredients of HLS were also determined by high-performance liquid chromatography (HPLC).Results: HLS could alleviate the depression-like behavior of the model rats. Biochemical analysis showed that HLS enhanced the levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in the hippocampus and diminished these in the serum of the CUMS rats. HLS could also decrease the concentration of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and β-endorphin (β-EP) in blood. The pathohistological examination revealed that the hippocampus and adrenal gland were improved after treatment with HLS.Conclusions: This study concluded that HLS could alleviate depression-like behaviors in the rats exposed to CUMS, and the potential mechanism may be related to the regulation of the monoamine neurotransmitters, the hypothalamic–pituitary–adrenal (HPA) axis, and the β-EP. These findings hint that HLS is likely to be a potentially effective agent for treating depression.
Cinnamomum zeylanicum Extract and its Bioactive Component Cinnamaldehyde Show Anti-Tumor Effects via Inhibition of Multiple Cellular Pathways
Authors: Aggarwal Sadhna , Bhadana Kanchan , Singh Baldeep , Rawat Meenakshi , Mohammad Taj , Al-Keridis Lamya Ahmed , Alshammari Nawaf , Hassan Md. Imtaiyaz , Das Satya N. 
Published: June 2022

Cinnamomum zeylanicum is a tropical plant with traditional medicinal significance that possesses antimicrobial, antifungal, anti-parasitic, and anti-tumor properties. Here, we have elucidated the anti-tumor effects of Cinnamomum zeylanicum extract (CZE) and its bioactive compound cinnamaldehyde (CIN) on oral cancer and elucidated underlying molecular mechanisms. Anti-tumor activities of CZE and CIN were demonstrated by various in vitro experiments on oral cancer cells (SCC-4, SCC-9, SCC-25). The cell proliferation, growth, cell cycle arrest, apoptosis, and autophagy were analyzed by MTT, clonogenic assay, propidium iodide, annexin-V-PI, DAPI, and acridine orange staining, respectively. The binding affinity of CIN towards dihydrofolate reductase and p38-MAP kinase alpha was analyzed by molecular docking. Western blot assay was performed to assess the alteration in the expression of various proteins. CZE and CIN treatment significantly inhibited the growth and proliferation of oral cancer cells in a dose-dependent manner. These treatments further induced apoptosis, cell cycle arrest, and autophagy. CZE and CIN inhibited the invasion and cytoplasmic translocation of NF-κB in these cell lines. CIN showed a high affinity to MAP kinase P38 alpha and dihydrofolate reductase with binding affinities of −6.8 and −5.9 kcal/mol, respectively. The cancer cells showed a decreased expression of various PI3k-AKT-mTOR pathways related to VEGF, COX-2, Bcl-2, NF-κB, and proteins post-treatment.
Microfluidic and Static Organotypic Culture Systems to Support Ex Vivo Spermatogenesis From Prepubertal Porcine Testicular Tissue: A Comparative Study
Authors: Kanbar Marc , de Michele Francesca , Poels Jonathan , Van Loo Stéphanie , Giudice Maria Grazia , Gilet Tristan , Wyns Christine 
Published: June 2022

Background:In vitro maturation of immature testicular tissue (ITT) cryopreserved for fertility preservation is a promising fertility restoration strategy. Organotypic tissue culture proved successful in mice, leading to live births. In larger mammals, including humans, efficiently reproducing spermatogenesis ex vivo remains challenging. With advances in biomaterials technology, culture systems are becoming more complex to better mimic in vivo conditions. Along with improving culture media components, optimizing physical culture conditions (e.g., tissue perfusion, oxygen diffusion) also needs to be considered. Recent studies in mice showed that by using silicone-based hybrid culture systems, the efficiency of spermatogenesis can be improved. Such systems have not been reported for ITT of large mammals.Methods: Four different organotypic tissue culture systems were compared: static i.e., polytetrafluoroethylene membrane inserts (OT), agarose gel (AG) and agarose gel with polydimethylsiloxane chamber (AGPC), and dynamic i.e., microfluidic (MF). OT served as control. Porcine ITT fragments were cultured over a 30-day period using a single culture medium. Analyses were performed at days (d) 0, 5, 10, 20 and 30. Seminiferous tubule (ST) integrity, diameters, and tissue core integrity were evaluated on histology. Immunohistochemistry was used to identify germ cells (PGP9.5, VASA, SYCP3, CREM), somatic cells (SOX9, INSL3) and proliferating cells (Ki67), and to assess oxidative stress (MDA) and apoptosis (C-Caspase3). Testosterone was measured in supernatants using ELISA.Results: ITT fragments survived and grew in all systems. ST diameters, and Sertoli cell (SOX9) numbers increased, meiotic (SYCP3) and post-meiotic (CREM) germ cells were generated, and testosterone was secreted. When compared to control (OT), significantly larger STs (d10 through d30), better tissue core integrity (d5 through d20), higher numbers of undifferentiated spermatogonia (d30), meiotic and post-meiotic germ cells (SYCP3: d20 and 30, CREM: d20) were observed in the AGPC system. Apoptosis, lipid peroxidation (MDA), ST integrity, proliferating germ cell (Ki67/VASA) numbers, Leydig cell (INSL3) numbers and testosterone levels were not significantly different between systems.Conclusions: Using a modified culture system (AGPC), germ cell survival and the efficiency of porcine germ cell differentiation were moderately improved ex vivo. We assume that further optimization can be obtained with concomitant modifications in culture media components.
All Roads Lead to Rome: Diverse Etiologies of Tricuspid Regurgitation Create a Predictable Constellation of Right Ventricular Shape Changes
Authors: Orkild Benjamin A. , Zenger Brian , Iyer Krithika , Rupp Lindsay C. , Ibrahim Majd M , Khashani Atefeh G. , Perez Maura D. , Foote Markus D. , Bergquist Jake A. , Morris Alan K. , Kim Jiwon J. , Steinberg Benjamin A. , Selzman Craig , Ratcliffe Mark B. , MacLeod Rob S. , Elhabian Shireen , Morgan Ashley E. 
Published: June 2022

Introduction:Myriad disorders cause right ventricular (RV) dilation and lead to tricuspid regurgitation (TR). Because the thin-walled, flexible RV is mechanically coupled to the pulmonary circulation and the left ventricular septum, it distorts with any disturbance in the cardiopulmonary system. TR, therefore, can result from pulmonary hypertension, left heart failure, or intrinsic RV dysfunction; but once it occurs, TR initiates a cycle of worsening RV volume overload, potentially progressing to right heart failure. Characteristic three-dimensional RV shape-changes from this process, and changes particular to individual TR causes, have not been defined in detail.Methods:Cardiac MRI was obtained in 6 healthy volunteers, 41 patients with ≥ moderate TR, and 31 control patients with cardiac disease without TR. The mean shape of each group was constructed using a three-dimensional statistical shape model via the particle-based shape modeling approach. Changes in shape were examined across pulmonary hypertension and congestive heart failure subgroups using principal component analysis (PCA). A logistic regression approach based on these PCA modes identified patients with TR using RV shape alone.Results:Mean RV shape in patients with TR exhibited free wall bulging, narrowing of the base, and blunting of the RV apex compared to controls (p<0.05). Using four primary PCA modes, a logistic regression algorithm identified patients with TR correctly with 82% recall and 87% precision. In patients with pulmonary hypertension without TR, RV shape was narrower and more streamlined than in healthy volunteers. However, in RVs with TR and pulmonary hypertension, overall RV shape continued to demonstrate the free wall bulging characteristic of TR. In the subgroup of patients with congestive heart failure without TR, this intermediate state of RV muscular hypertrophy was not present.Conclusion:The multiple causes of TR examined in this study changed RV shape in similar ways. Logistic regression classification based on these shape changes reliably identified patients with TR regardless of etiology. Furthermore, pulmonary hypertension without TR had unique shape features, described here as the “well compensated” RV. These results suggest shape modeling as a promising tool for defining severity of RV disease and risk of decompensation, particularly in patients with pulmonary hypertension.
Effect of a Single Simulated 500 m Saturation Dive on Lung Function
Authors: Lian Ningfang , Wang Sijiao , Hu Lijuan , Xue Liping , Gong Ying , Li Li , Yang Yanjie , Zhu Lei 
Published: June 2022

Background: Whether deep saturation diving causes injury to lung function remains controversial and the mechanism is unclear. The present study aimed to evaluate the effects of a 500 m simulated single saturation dive on lung function.Methods: A retrospective study was performed in nine professional divers who spent 176 h in a high-pressure environment simulating a depth of 500-m saturation dive (51 atm, 5.02 Mpa). Pulmonary function parameters were investigated and compared before and on 3 days after the dive.Results: Nine professional divers aged (36 ± 7) years were enrolled. Three days after the dive, the parameters related to expiratory flow (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)) were decreased; the parameters related to small airway function (forced expiratory flow at 50%, 75% of FVC exhaled and forced mid-expiratory flow) were decreased compared with those before the dive (both p &lt; 0.05). Additionally, after the dive, the parameters related to pulmonary diffusion function were decreased compared with those before the dive (both p &lt; 0.05). The parameters related to lung volume (residual volume, vital capacity and total lung volume) and those related to respiratory exertion (peak expiratory flow and forced expiratory flow at 75% of FVC exhaled) were not significantly different between after and before the dive. Two divers with small airway dysfunction before the dive had obstructive ventilatory dysfunction after the dive. Additionally, mild obstructive ventilatory dysfunction in three divers before the dive became severe after the dive. After a bronchial dilation test, five divers showed improvement of FEV1, which ranged from 0.10 to 0.55 L. Chest radiographs and echocardiography of all divers were normal after diving.Conclusion: 500 m simulated saturation diving induces a decrease in small airway function and diffusion function. This injury may be associated with small airway and diffusion membrane lesions.
“Today I Can Look in the Mirror and Like Myself”: Effects of a Trauma-Informed Mindful Recovery Program on Self-Compassion
Authors: Moore Sarah K. , Okst Kayley , Smith Lydia , Fatkin Thomas , Creedon Timothy , Fredericksen A. Kiera , Gawande Richa , Schuman-Olivier Zev 
Published: June 2022

BackgroundOpioid-related deaths continue to rise. Psychological trauma is commonly comorbid with Opioid Use Disorder (OUD). Adverse childhood experiences can disrupt the development of emotion regulation, increasing risk of substance use. Self-compassion may reduce OUD risk and outcomes by facilitating emotion regulation, decreasing the toxicity of shame, and reducing internalized stigma that can hinder recovery. Mindfulness practice enhances self-compassion.MethodsThis study is part of a pilot (N = 18) of the Mindful Recovery OUD Care Continuum (M-ROCC) during buprenorphine office-based opioid treatment (OBOT). The present study was conducted to gain a deeper understanding of the intervention’s effects on self-compassion development, and to explore differential changes in self-compassion during the intervention among participants with varying intensity of trauma exposure measured by high levels of childhood adversity (defined by 4+ adverse childhood experiences (ACEs) at baseline). We conducted secondary analyses of a subset of qualitative interview data (N = 11 unique participants) collected for the pilot study (weeks 4 and 24, 14 total interviews) to elaborate upon changes in Self-Compassion Scale (SCS-SF) scores.ResultsIn the primary pilot study, participants’ mean SCS-SF scores shifted significantly from baseline to week 24, β = 0.22, p = 0.028. This change is elaborated upon through interviews. Despite pervasive challenges to becoming more self-compassionate (e.g., trauma histories and substance use), participants reported increased compassionate self-responding and decreased uncompassionate self-responding. Mindfulness training was identified as the primary mechanism underlying the shift. Kindness to self and others and—to a lesser extent an increased sense of common humanity—were also identified as key to overall self-compassion. Compared to those in the lower ACEs group, participants in the higher ACEs group tended to have lower baseline self-compassion scores (d = 1.09, p = 0.055).ConclusionM-ROCC may increase self-compassion among patients with OUD during OBOT by increasing compassionate, and decreasing uncompassionate, self-responding. Patients with OUD with greater childhood adversity tended to have lower levels of self-compassion, which improved with M-ROCC. Future trials with larger samples are needed to confirm these potential outcomes, mechanisms, and differential impacts between ACEs subgroups.