bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological basis of bergapten in gastrointestinal diseases focusing on H+/K+ ATPase and voltage-gated calcium channel inhibition: A toxicological evaluation on vital organs
Authors: Aslam Huma , Khan Arif-ullah , Qazi Neelum Gul , Ali Fawad , Hassan Syed Shams ul , Bungau Simona 
Published: November 2022

Aim and objectives: This study aimed to establish a pharmacological basis for evaluating the effects of bergapten (5-methoxypsoralen) in gastrointestinal diseases and assessment of its toxicological profile.Methods: The pharmacokinetic profile was evaluated using the SwissADME tool. AUTODOCK and PyRx were used for evaluating the binding affinities. The obtained results were further investigated for a post-dock analysis using Discovery Studio Visualizer 2016. The Desmond software package was used to conduct molecular dynamic simulations of best bound poses. Bergapten was further investigated for antidiarrheal, anti-secretory, charcoal meal transit time, anti-ulcer, anti-H. pylori activity.Results: Bergapten at a dose of 50, 100, and 200 mg/kg was proved effective in reducing diarrheal secretions, intestinal secretions, and distance moved by charcoal meal. Bergapten at the aforementioned doses acts as a gastroprotective agent in the ethanol-induced ulcer model that can be attributed to its effectiveness against H. pylori. Bergapten shows concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions in the isolated rabbit jejunum model; the Ca2+ concentration–response curves (CRCs) were shifted to the right showing potentiating effect similar to papaverine. For molecular investigation, the H+/K+ ATPase inhibitory assay indicated inhibition of the pump comparable to omeprazole. Oxidative stress markers GST, GSH, and catalase showed increased expression, whereas the expression of LPO (lipid peroxidation) was reduced. Histopathological examination indicated marked improvement in cellular morphology. ELISA and western blot confirmed the reduction in inflammatory mediator expression. RT-PCR reduced the mRNA expression level of H+/K+ ATPase, confirming inhibition of the pump. The toxicological profile of bergapten was evaluated by an acute toxicity assay and evaluated for behavioral analysis, and the vital organs were used to analyze biochemical, hematological, and histopathological examination.Conclusion: Bergapten at the tested doses proved to be an antioxidant, anti-inflammatory, anti-ulcer, and antidiarrheal agent and relatively safe in acute toxicity assay.
Mechano-growth factor E-domain modulates cardiac contractile function through 14-3-3 protein interactomes
Authors: Solís Christopher , Thompson Walter C. , Peña James R. , McDermott-Roe Christopher , Langa Paulina , Warren Chad M. , Chrzanowska Magdalena , Wolska Beata M. , Solaro R. John , Pieter Detombe  , Goldspink Paul H. 
Published: November 2022

In the heart, alternative splicing of the igf-I gene produces two isoforms: IGF-IEa and IGF-IEc, (Mechano-growth factor, MGF). The sequence divergence between their E-domain regions suggests differential isoform function. To define the biological actions of MGF’s E-domain, we performed in silico analysis of the unique C-terminal sequence and identified a phosphorylation consensus site residing within a putative 14-3-3 binding motif. To test the functional significance of Ser 18 phosphorylation, phospho-mimetic (S/E18) and phospho-null (S/A18) peptides were delivered to mice at different doses for 2 weeks. Cardiovascular function was measured using echocardiography and a pressure-volume catheter. At the lowest (2.25 mg/kg/day) and highest (9 mg/kg/day) doses, the peptides produced a depression in systolic and diastolic parameters. However, at 4.5 mg/kg/day the peptides produced opposing effects on cardiac function. Fractional shortening analysis also showed a similar trend, but with no significant change in cardiac geometry. Microarray analysis discovered 21 genes (FDR p &lt; 0.01), that were expressed accordant with the opposing effects on contractile function at 4.5 mg/kg/day, with the nuclear receptor subfamily 4 group A member 2 (Nr4a2) identified as a potential target of peptide regulation. Testing the regulation of the Nr4a family, showed the E-domain peptides modulate Nr4a gene expression following membrane depolarization with KCl in vitro. To determine the potential role of 14-3-3 proteins, we examined 14-3-3 isoform expression and distribution. 14-3-3γ localized to the myofilaments in neonatal cardiac myocytes, the cardiac myocytes and myofilament extracts from the adult heart. Thermal shift analysis of recombinant 14-3-3γ protein showed the S/A18 peptide destabilized 14-3-3γ folding. Also, the S/A18 peptide significantly inhibited 14-3-3γ’s ability to interact with myosin binding protein C (MYPC3) and phospholamban (PLN) in heart lysates from dobutamine injected mice. Conversely, the S/E18 peptide showed no effect on 14-3-3γ stability, did not inhibit 14-3-3γ’s interaction with PLN but did inhibit the interaction with MYPC3. Replacing the glutamic acid with a phosphate group on Ser 18 (pSer18), significantly increased 14-3-3γ protein stability. We conclude that the state of Ser 18 phosphorylation within the 14-3-3 binding motif of MGF’s E-domain, modulates protein-protein interactions within the 14-3-3γ interactome, which includes proteins involved in the regulation of contractile function.
Pigment epithelium-derived factor is an interleukin-6 antagonist in the RPE: Insight of structure-function relationships
Authors: Bernardo-Colón Alexandra , Lerner Miriam , Becerra S. Patricia 
Published: November 2022

Retinal and choroidal inflammatory lesions increase the levels of the pro-inflammatory cytokine interleukin-6 (IL-6). Pigment epithelium-derived factor (PEDF) has anti-inflammatory properties, but it is not known if it can prevent the production of IL-6 by the retinal pigment epithelium. To investigate the anti-inflammatory effects of PEDF in the RPE, we used human ARPE-19 cells stimulated with human recombinant tumor necrosis factor-alpha (TNF-α) to induce overexpression of the IL6 gene. We found that the viability of ARPE-19 cells decreased by 22% with TNF-α at 10 ng/ml, being drastically decreased at ≥50 ng/ml. TNF-α at 5–100 ng/ml elevated the production and secretion of IL-6 protein, as measured by ELISA. To challenge the TNF-α-mediated stimulation of IL-6, we used recombinant human PEDF protein. PEDF at 100 nM recovered the TNF-α-mediated loss of cell viability and repressed IL-6 gene expression as determined by RT-PCR. PEDF at 10–100 nM attenuated the IL-6 protein secretion in a dose dependent fashion (IC50 = 65 nM), being abolished with 100 nM PEDF. To map the region that confers the IL-6 blocking effect to the PEDF polypeptide, we used chemically synthesized peptides designed from its biologically active domains, pro-death 34-mer, and pro-survival 44-mer and 17-mer (H105A), to challenge the IL-6 overproduction. The pro-survival peptides recovered the TNF-α-mediated cell viability loss, and inhibited IL-6 secretion, while the 34-mer did not have an effect, suggesting a role for the pro-survival domain in blocking TNF-α-mediated cell death and IL-6 stimulation. Our findings position PEDF as a novel antagonistic agent of IL-6 production in RPE cells, underscoring its use for the management of retinal disease-related inflammation.
Destructive interparental conflict affects Chinese children’s emotional and behavioral problems: Indirect pathways via parent–child attachment and emotional insecurity
Authors: Yang Meirong , Qi Huan , Meng Zhaoyan , Duan Xiangfei , Zhang Libin 
Published: November 2022

BackgroundPrevious studies have demonstrated that destructive interparental conflict (IPC) is closely related to the emergence of emotional and behavioral problems in adolescents. In addition, in the family system, such conflict also affects the patent–child attachment relationship and emotional insecurity of adolescents.ObjectivesThis study mainly explores the relationship between destructive interparental conflict and adolescents’ emotional and behavioral problems, focuses on the role of parent–child attachment and emotional insecurity, and analyzes whether this relationality plays multiple mediating roles in the influence of destructive interparental conflict on emotional and behavioral problems.MethodsData for the study were obtained through a questionnaire survey conducted on 524 Chinese adolescents from primary and junior high school.ResultsStructural equation modeling was conducted to test direct and indirect pathways between destructive interparental conflict and Chinese adolescents’ emotional and behavioral problems. Destructive IPC negatively predicted parent–child attachment and parent–child attachment negatively predicted emotional and behavioral problems. Destructive Interparental conflict positively predicted emotional insecurity and emotional insecurity positively predicted emotional and behavioral problems.DiscussionThe results show that: (1) Parent–child attachment negatively predicted emotional and behavioral problems, and emotional insecurity positively predicted the same. (2) Parent–child attachment and emotional insecurity act in a multiple mediating role between destructive IPC and adolescents’ emotional and behavioral problems. (3) Parent–child attachment and emotional insecurity constitute two indirect pathways between destructive IPC and adolescents’ emotional and behavioral problems, respectively.ConclusionDestructive IPC can adversely affect emotional and behavioral problems among adolescents; destructive IPC plays a damaging role in their emotional security and parent–child attachment, consequently effecting emotional and behavioral problems.
Structural, functional, and metabolic signatures of postpartum depression: A systematic review
Authors: Horáková Anna , Němcová Hana , Mohr Pavel , Sebela Antonin 
Published: November 2022

ObjectivePostpartum depression (PPD) is a serious condition with debilitating consequences for the mother, offspring, and the whole family. The scope of negative outcomes of PPD highlights the need to specify effective diagnostics and treatment which might differ from major depressive disorder (MDD). In order to improve our clinical care, we need to better understand the underlying neuropathological mechanisms of PPD. Therefore, we conducted a systematic review of published neuroimaging studies assessing functional, structural, and metabolic correlates of PPD.MethodsRelevant papers were identified using a search code for English-written studies in the PubMed, Scopus, and Web of Science databases published by March 2022. Included were studies with structural magnetic resonance imaging, functional magnetic resonance imaging, both resting-state and task-related, magnetic resonance spectroscopy, or positron emission tomography. The findings were analyzed to assess signatures in PPD-diagnosed women compared to healthy controls. The review protocol was registered in PROSPERO (CRD42022313794).ResultsThe total of 3,368 references were initially identified. After the removal of duplicates and non-applicable papers, the search yielded 74 full-text studies assessed for eligibility. Of them, 26 met the inclusion criteria and their findings were analyzed and synthesized. The results showed consistent functional, structural, and metabolic changes in the default mode network and the salient network in women with PPD. During emotion-related tasks, PPD was associated with changes in the corticolimbic system activity, especially the amygdala.DiscussionThis review offers a comprehensive summary of neuroimaging signatures in PPD-diagnosed women. It indicates the brain regions and networks which show functional, structural, and metabolic changes. Our findings offer better understanding of the nature of PPD, which clearly copies some features of MDD, while differs in others.
Evaluating occupational exposures of dental nurses: A retrospective study
Authors: Yuan Hongmei , Shi Rui , Chen Wenwen , Ma Ying , Liu Zhiqing , Liu Fan , Yang Jingmei 
Published: November 2022

ObjectiveThe objective of this study was to investigate occupational blood-borne pathogen exposure among dental nurses and their attitudes toward infected patients, as well as the effectiveness of the training course, to provide a scientific basis for improving the quality of safety management in the dental hospital.Materials and methodsThe study was conducted using questionnaires administered from November 2019 to December 2019 in three hospitals in Sichuan Province, China. Frequencies for answers were calculated and presented as percentages.ResultsIn total, 257 valid questionnaires were returned. Most (61.9%) nurses stated that they were involved in occupational exposure. Among them, 154 had experienced sharp injuries, and the syringe needle was the most common instrument for injuries (45.8%). Twenty-two individuals had mucosal exposure, and the proportion of eye exposure was the highest (90.9%). Only associations between training and mucosal membrane exposure were found; however, the relevance was weak (r = 0.141). Of the participants, 86.4% felt morally responsible for taking care of patients with infectious diseases, and most (92.6%) said they would continue with this career.ConclusionOccupational exposure, particularly to sharp injuries, was common in medical care among dental nurses; however, vocational training had little effect on their incidence. As dental nurses still have positive attitudes toward patients with infectious diseases, more effective training should be conducted.
Latent profile analysis of security among patients with COVID-19 infection in mobile cabin hospitals and its relationship with psychological capital
Authors: Wu Chao , Yan Jia-ran , He Chun-yan , Wu Jing , Zhang Yin-juan , Du Juan , Lin Ya-wei , Zhang Yu-hai , Heng Chun-ni , Lang Hong-juan 
Published: November 2022

AimCOVID-19 patients' security is related to their mental health. However, the classification of this group's sense of security is still unclear. The aim of our research is to clarify the subtypes of security of patients infected with COVID-19, explore the factors affecting profile membership, and examine the relationship between security and psychological capital for the purpose of providing a reference for improving patients' sense of security and mental health.MethodsA total of 650 COVID-19 patients in a mobile cabin hospital were selected for a cross-sectional survey from April to May 2022. They completed online self-report questionnaires that included a demographic questionnaire, security scale, and psychological capital scale. Data analysis included latent profile analysis, variance analysis, the Chi-square test, multiple comparisons, multivariate logistical regression, and hierarchical regression analysis.ResultsThree latent profiles were identified—low security (Class 1), moderate security (Class 2), and high security (Class 3)—accounting for 12.00, 49.51, and 38.49% of the total surveyed patients, respectively. In terms of the score of security and its two dimensions, Class 3 was higher than Class 2, and Class 2 was higher than Class 1 (all P &lt; 0.001). Patients with difficulty falling asleep, sleep quality as usual, and lower tenacity were more likely to be grouped into Class 1 rather than Class 3; Patients from families with a per capita monthly household income &lt;3,000 and lower self-efficacy and hope were more likely to be grouped into Classes 1 and 2 than into Class 3. Psychological capital was an important predictor of security, which could independently explain 18.70% of the variation in the patients' security.ConclusionsSecurity has different classification features among patients with COVID-19 infection in mobile cabin hospitals. The security of over half of the patients surveyed is at the lower or middle level, and psychological capital is an important predictor of the patients' security. Medical staff should actively pay attention to patients with low security and help them to improve their security level and psychological capital.
Epidemiological characteristics of occupational chemical poisonings in Zhejiang, China from 2006 to 2020: A descriptive analysis
Authors: Zhou Lifang , Wei Fang , Fang Xinglin , Zhang Yixin , Hu Yong , Lou Xiaoming , Xue Panqi , Zou Hua 
Published: November 2022

ObjectiveAs the second most common occupational disease in China, occupational poisoning is one of the major public health problems that seriously affect workers' health. This study aimed to investigate the epidemiological and occupational characteristics of acute and chronic occupational poisoning cases in Zhejiang Province, so as to provide a scientific basis for proposing intervention measures and preventive strategies of occupational poisoning.MethodsThe data on occupational poisoning cases in Zhejiang Province from 2006 to 2020 was derived from the National Occupational Disease Network Direct Report System. A descriptive statistical analysis was employed on this data utilizing R software.ResultsFrom 2006 to 2020, 1,008 occupational poisoning cases were reported in Zhejiang Province, with a downward trend since 2007. Of these cases, 81.94% were chronic poisoning and 18.06% were acute poisoning. Ningbo reported the most occupational poisoning cases among the 11 cities in Zhejiang Province, accounting for 20.34% of the total cases. Besides, the occupational poisoning cases in Wenzhou, Jiaxing, and Shaoxing also accounted for 18.15%, 18.06%, and 17.76% of the total number of cases, respectively. Occupational poisoning in male were 693 cases and in female 315 cases. Most of the occupational poisoning cases studied involved people aged between 40 and 49 years (38.19%). The length of work in chronic occupational poisoning cases was significantly higher than that of acute occupational poisoning cases (P &lt; 0.05). Benzene and lead and its compounds (excluding tetraethyl lead) were the major toxicants causing occupational poisoning. More than 60% of occupational poisoning cases were reported in private enterprises. Meanwhile, over 90% of the cases were distributed in medium enterprises and small enterprises. The type of industry with the most occupational poisoning cases was the manufacturing industry.ConclusionAlthough the cases of occupational poisoning in Zhejiang Province have declined, more comprehensive and effective prevention and control measures are still needed. More attention ought to be paid to the management of key points according to the epidemiological and occupational characteristics of occupational poisoning cases.
Nomogram based on spleen volume expansion rate predicts esophagogastric varices bleeding risk in patients with hepatitis B liver cirrhosis
Authors: Li Jianghong , Li Junjie , Ji Qian , Wang Zhenglu , Wang Honghai , Zhang Sai , Fan Shunli , Wang Hao , Kong Dejun , Ren Jiashu , Zhou Yunhui , Yang Ruining , Zheng Hong 
Published: November 2022

BackgroundWe aimed to explore the risk factors for hemorrhage of esophagogastric varices (EGVs) in patients with hepatitis B cirrhosis and to construct a novel nomogram model based on the spleen volume expansion rate to predict the risk of esophagogastric varices bleeding.MethodsUnivariate and multivariate logistic regression analysis was used to analyze the risk factors for EGVs bleeding. Nomograms were established based on the multivariate analysis results. The predictive accuracy of the nomograms was assessed using the area under the curve (AUC or C-index) of the receiver operating characteristic (ROC) and calibration curves. Decision curve analysis was used to determine the clinical benefit of the nomogram. We created a nomogram of the best predictive models.ResultsA total of 142 patients' hepatitis B cirrhosis with esophagogastric varices were included in this study, of whom 85 (59.9%) had a history of EGVs bleeding and 57 (40.1%) had no EGVs bleeding. The spleen volume expansion rate, serum sodium levels (mmol/L), hemoglobin levels (g/L), and prothrombin time (s) were independent predictors for EGVs bleeding in patients with hepatitis B liver cirrhosis (P &lt; 0.05). The above predictors were included in the nomogram prediction model. The area under the ROC curve (AUROC) of the nomogram was 0.781, the C-index obtained by internal validation was 0.757, and the calibration prediction curve fit well with the ideal curve. The AUROCs of the PLT-MELD and APRI were 0.648 and 0.548, respectively.ConclusionIn this study, a novel nomogram for predicting the risk of EGVs bleeding in patients with hepatitis B cirrhosis was successfully constructed by combining the spleen volume expansion rate, serum sodium levels, hemoglobin levels, and prothrombin time. The predictive model can provide clinicians with a reference to help them make clinical decisions.
Influence of fluid balance on postoperative outcomes after hepatic resection in patients with left ventricular diastolic dysfunction
Authors: Shin Jungho , Suh Suk-Won 
Published: November 2022

ObjectiveThe maintenance of low central venous pressure (CVP) during hepatic resection is associated with a reduction in estimated blood loss. After completion of the hepatic parenchymal transection, fluid is rapidly administered to replace the surgical blood loss and fluid deficit to prevent subsequent organ injury risk. However, this perioperative fluid strategy may influence on the postoperative outcomes of patients with left ventricular diastolic dysfunction (LVDD) who cannot tolerate volume adjustment.MethodA total of 206 patients with who underwent hepatic resection between March 2015 and February 2021 were evaluated. LVDD was defined according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2016 recommendations as LVDD (group A, n = 39), or normal LV diastolic function and indeterminate decision (group B, n = 153). We compared the clinical outcomes of patients between two groups, and then analyzed the risk factors for postoperative complications.ResultPostoperative acute kidney injury (AKI, 10.3% vs. 1.3%, P = 0.004) and pleural effusion or edema (51.3% vs. 30.1%, P = 0.013) were more common in group A than in group B. Further, creatinine levels from postoperative day 1 to day 7 were significantly higher and daily urine outputs at postoperative day 1 (P = 0.038) and day 2 (P = 0.025) were significantly lower in group A than in group B. LVDD was the only significant risk factor for postoperative AKI after hepatic resection (odds ratio, 10.181; 95% confidence interval, 1.570–66.011, P = 0.015).ConclusionsThe rates of renal dysfunction and pulmonary complications after hepatic resection are higher in patients with LVDD than in those with normal LV diastolic function. Thus, these patients require individualized fluid management.