bluuebunny/crossref_metadata_2025 huggingface dataset:
The Peptidyl-Prolyl cis-trans isomerase, Pin1, associates with Protein Kinase C θ via a critical Phospho-Thr-Pro motif in the V3 regulatory domain
Authors: Anto Nikhil Ponnoor , Muraleedharan Amitha , Nath Pulak Ranjan , Sun Zuoming , Keasar Chen , Livneh Etta , Braiman Alex , Altman Amnon , Kong Kok-Fai , Isakov Noah
Published: March 2023

Protein kinase C-θ (PKCθ) is a member of the novel PKC subfamily known for its selective and predominant expression in T lymphocytes where it regulates essential functions required for T cell activation and proliferation. Our previous studies provided a mechanistic explanation for the recruitment of PKCθ to the center of the immunological synapse (IS) by demonstrating that a proline-rich (PR) motif within the V3 region in the regulatory domain of PKCθ is necessary and sufficient for PKCθ IS localization and function. Herein, we highlight the importance of Thr335-Pro residue in the PR motif, the phosphorylation of which is key in the activation of PKCθ and its subsequent IS localization. We demonstrate that the phospho-Thr335-Pro motif serves as a putative binding site for the peptidyl-prolyl cis-trans isomerase (PPIase), Pin1, an enzyme that specifically recognizes peptide bonds at phospho-Ser/Thr-Pro motifs. Binding assays revealed that mutagenesis of PKCθ-Thr335-to-Ala abolished the ability of PKCθ to interact with Pin1, while Thr335 replacement by a Glu phosphomimetic, restored PKCθ binding to Pin1, suggesting that Pin1-PKCθ association is contingent upon the phosphorylation of the PKCθ-Thr335-Pro motif. Similarly, the Pin1 mutant, R17A, failed to associate with PKCθ, suggesting that the integrity of the Pin1 N-terminal WW domain is a requisite for Pin1-PKCθ interaction. In silico docking studies underpinned the role of critical residues in the Pin1-WW domain and the PKCθ phospho-Thr335-Pro motif, to form a stable interaction between Pin1 and PKCθ. Furthermore, TCR crosslinking in human Jurkat T cells and C57BL/6J mouse-derived splenic T cells promoted a rapid and transient formation of Pin1-PKCθ complexes, which followed a T cell activation-dependent temporal kinetic, suggesting a role for Pin1 in PKCθ-dependent early activation events in TCR-triggered T cells. PPIases that belong to other subfamilies, i.e., cyclophilin A or FK506-binding protein, failed to associate with PKCθ, indicating the specificity of the Pin1-PKCθ association. Fluorescent cell staining and imaging analyses demonstrated that TCR/CD3 triggering promotes the colocalization of PKCθ and Pin1 at the cell membrane. Furthermore, interaction of influenza hemagglutinin peptide (HA307-319)-specific T cells with antigen-fed antigen presenting cells (APCs) led to colocalization of PKCθ and Pin1 at the center of the IS. Together, we point to an uncovered function for the Thr335-Pro motif within the PKCθ-V3 regulatory domain to serve as a priming site for its activation upon phosphorylation and highlight its tenability to serve as a regulatory site for the Pin1 cis-trans isomerase.
Associations between bullous pemphigoid and hematological diseases: Literature review on mechanistic connections and possible treatments
Authors: Yang Yuyan , Zhao Wenling , Yang Nan , Cui Shengnan , Jin Hongzhong , Li Li
Published: March 2023

Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.
Marine heatwaves characteristics in the Mediterranean Sea: Case study the 2019 heatwave events
Authors: Hamdeno Manal , Alvera-Azcaráte Aida
Published: March 2023

Marine Heatwaves (MHWs) are considered one of the main consequences of global warming. MHWs negatively affect ecosystems, threaten economies, and intensify storms. In this work, we investigated the main characteristics of MHWs in the Mediterranean Sea from 1982 to 2020 and examined the relationship between their frequency and teleconnection patterns (e.g., East Atlantic Pattern (EAP) and East Atlantic/Western Russian Pattern (EATL/WRUS)). We then focused on the most intense MHW events that occurred in 2019 in the western Mediterranean Sea (WMB) and eastern Mediterranean Sea (EMB) by examining the link between the SST anomaly (SSTA) and various atmospheric forcings during these events. Our results showed that MHWs were more frequent and intense in the WMB than in the EMB on temporal and spatial scales, while the duration of MHWs was longer in the EMB. The trend of MHW frequency and duration in the Mediterranean Sea between 1982 and 2020 was about 1.3 ± 0.25 events/decade and 3.6 ± 1.16 days/decade, respectively. More than half of all MHW events in the Mediterranean Sea were recorded in the last decade (2011-2020). The results also showed that the EAP plays an important role in modulating MHW frequency in the Mediterranean Sea, with a strong positive correlation of 0.74, while the EATL/WRUS was strongly negatively correlated with MHW frequency in the EMB, with a correlation of about -0.60. In 2019, six MHW events were observed in the WMB, three of which were classified as strong events (SST exceeded two times the climatological threshold), while two events were detected and classified as strong events in the EMB. In the WMB, the 2019 MHWs extended to a depth of about 20 meters into the water column, while the MHWs in the EMB extended to greater depths of over 50 meters. The strong MHW events in the WMB were associated with a large positive heat flux anomaly and a shallow mixed layer. In the EMB, the high SSTA associated with MHW events caused heat loss from the ocean to the atmosphere and was associated with a shallow mixed layer and anomalously low mean sea level pressure. Finally, a negative relationship between the SSTA and surface Chl-a concentrations was observed during the 2019 MHW events. This negative influence of MHWs on Chl-a was more pronounced in the WMB than in the EMB, suggesting that the WMB MHW events were intense enough to infer a response to chlorophyll-a concentrations.
Chronic cold-stress induced histopathological changes, oxidative stress, and alterations in liver functions and nutrient composition of hybrid red tilapia and the potential protection of unsaturated fatty acids
Authors: Refaey Mohamed M. , Mehrim Ahmed I. , El-Komy Magda M. , Zenhom Osama A. , Mansour Abdallah Tageldein
Published: March 2023

The hybrid red tilapia (♂Oreochromis niloticus × ♀O. mossambicus) is a promising tilapia fish with high growth rate, market acceptability, and the ability to live in a wide range of salinities, but it is sensitive to low water temperature. Therefore, the objective of this experiment was to improve hybrid red tilapia resistance to chronic cold stress by increasing unsaturated fatty acids and evaluating their effects on fish body weight, hepatosomatic index (HSI), body nutrient composition, liver function enzymes, histopathological alterations, and biomarkers of oxidative stress in the gills and liver. For 98 days, fish were fed four diets based on two dietary fat sources: corn oil (a traditional source) and Aquafat-O® (a commercial product rich in high polyunsaturated fatty acids), in different ratios of 3:0 (T0), 2:1 (T1), 1:2 (T2), and 0:3 (T3), respectively. Subsequently, all groups (T0+, T1, T2, and T3) were subjected to water cold stress at 13 °C for 15 days, with half of the control group serving as a negative control (T0-; at a rearing water temperature of 25-26 °C). Chronic old stress caused significant reductions in fish body weight, HSI, aspartate transaminase and alanine transaminase activities, fat and energy contents, and oxidative stress biomarkers in the liver and gills. Red tilapia subjected to low temperatures showed severely altered histopathological conditions in the liver and gills. However, by gradually increasing the Aquafat-O® ratio in the diet, the negative effects of cold stress were mitigated. Thus, it could be concluded that the beneficial use of Aquafat-O® (as a promising fat source) at a percentage of up to 69.60 g kg-1 is necessary to cope with the cold-water stress for sensitive hybrid red tilapia.
Lichen myxedematosus associated with monoclonal gammopathy of undetermined significance: A case report and literature review
Authors: Huang Hua , Qian Shen-Xian
Published: March 2023

Lichen myxedematosus (LM) is an idiopathic cutaneous mucinosis disorder, and monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic plasma cell disease with a monoclonal increase in globulin. Patients with LM combined with monoclonal gammopathy are normally diagnosed with scleromyxedema. However, we report a case of generalized papules combined with MGUS in a 78-year-old man who was eventually diagnosed with atypical or intermediate forms of LM because it only involved the skin, and the pathological type was not consistent with scleromyxedema. Few cases of atypical or intermediate forms of LM have been reported, so the course of atypical or intermediate forms of LM is unpredictable. We report the diagnosis and treatment of a case of atypical forms of LM to discuss the current understanding of the disease, hoping to provide a reference for clinical research on this disease.
Application of artificial intelligence in diagnosis and treatment of colorectal cancer: A novel Prospect
Authors: Yin Zugang , Yao Chenhui , Zhang Limin , Qi Shaohua
Published: March 2023

In the past few decades, according to the rapid development of information technology, artificial intelligence (AI) has also made significant progress in the medical field. Colorectal cancer (CRC) is the third most diagnosed cancer worldwide, and its incidence and mortality rates are increasing yearly, especially in developing countries. This article reviews the latest progress in AI in diagnosing and treating CRC based on a systematic collection of previous literature. Most CRCs transform from polyp mutations. The computer-aided detection systems can significantly improve the polyp and adenoma detection rate by early colonoscopy screening, thereby lowering the possibility of mutating into CRC. Machine learning and bioinformatics analysis can help screen and identify more CRC biomarkers to provide the basis for non-invasive screening. The Convolutional neural networks can assist in reading histopathologic tissue images, reducing the experience difference among doctors. Various studies have shown that AI-based high-level auxiliary diagnostic systems can significantly improve the readability of medical images and help clinicians make more accurate diagnostic and therapeutic decisions. Moreover, Robotic surgery systems such as da Vinci have been more and more commonly used to treat CRC patients, according to their precise operating performance. The application of AI in neoadjuvant chemoradiotherapy has further improved the treatment and efficacy evaluation of CRC. In addition, AI represented by deep learning in gene sequencing research offers a new treatment option. All of these things have seen that AI has a promising prospect in the era of precision medicine.
Rapid discrimination of Shigella spp. and Escherichia coli via label-free surface enhanced Raman spectroscopy coupled with machine learning algorithms
Authors: Liu Wei , Tang Jia-Wei , Mou Jing-Yi , Lyu Jing-Wen , Di Yu-Wei , Liao Ya-Long , Luo Yan-Fei , Li Zheng-Kang , Wu Xiang , Wang Liang
Published: March 2023

Shigella and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens of diarrheal disease that is the second leading cause of childhood mortality globally. Currently, it is well known that Shigella spp., and E. coli are very closely related with many common characteristics. Evolutionarily speaking, Shigella spp., are positioned within the phylogenetic tree of E. coli. Therefore, discrimination of Shigella spp., from E. coli is very difficult. Many methods have been developed with the aim of differentiating the two species, which include but not limited to biochemical tests, nucleic acids amplification, and mass spectrometry, etc. However, these methods suffer from high false positive rates and complicated operation procedures, which requires the development of novel methods for accurate and rapid identification of Shigella spp., and E. coli. As a low-cost and non-invasive method, surface enhanced Raman spectroscopy (SERS) is currently under intensive study for its diagnostic potential in bacterial pathogens, which is worthy of further investigation for its application in bacterial discrimination. In this study, we focused on clinically isolated E. coli strains and Shigella species (spp.), that is, S. dysenteriae, S. boydii, S. flexneri, and S. sonnei, based on which SERS spectra were generated and characteristic peaks for Shigella spp., and E. coli were identified, revealing unique molecular components in the two bacterial groups. Further comparative analysis of machine learning algorithms showed that, the Convolutional Neural Network (CNN) achieved the best performance and robustness in bacterial discrimination capacity when compared with Random Forest (RF) and Support Vector Machine (SVM) algorithms. Taken together, this study confirmed that SERS paired with machine learning could achieve high accuracy in discriminating Shigella spp., from E. coli, which facilitated its application potential for diarrheal prevention and control in clinical settings.
Effect of acupuncture on the modulation of functional brain regions in migraine: A meta-analysis of fMRI studies
Authors: Li Mengyuan , Huang Haipeng , Yao Lin , Yang Hongmei , Ma Shiqi , Zheng Haizhu , Zhong Zhen , Yu Shuo , Yu Bin , Wang Hongfeng
Published: March 2023

Background

Acupuncture, a traditional Chinese medicine therapy, is an effective migraine treatment, especially in improving pain. In recent years, many acupuncture brain imaging studies have found significant changes in brain function following acupuncture treatment of migraine, providing a new perspective to elucidate the mechanism of action of acupuncture.

Objective

To analyse and summarize the effects of acupuncture on the modulation of specific patterns of brain region activity changes in migraine patients, thus providing a mechanism for treating migraine by acupuncture.

Methods

Chinese and English articles published up to May 2022 were searched in three English databases (PubMed, Embase and Cochrane) and four Chinese databases (China national knowledge infrastructure, CNKI; Chinese Biomedical Literature database, CBM; the Chongqing VIP database, VIP; and the Wanfang database, WF). A neuroimaging meta-analysis on ALFF, ReHo was performed on the included studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. Subgroup analyses were used to compare differences in brain regions between acupuncture and other groups. Meta-regression was used to explore the effect of demographic information and migraine alterations on brain imaging outcomes. Linear models were drawn using MATLAB 2018a, and visual graphs for quality evaluation were produced using R and RStudio software.

Results

A total of 7 studies comprising 236 patients in the treatment group and 173 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps to improve pain symptoms in patients with migraine. The left angular gyrus is hyperactivation, and the left superior frontal gyrus and the right superior frontal gyrus are hypoactivated. The migraine group showed hyperactivation in the corpus callosum compared to healthy controls.

Conclusion

Acupuncture can significantly regulate changes in brain regions in migraine patients. However, due to the experimental design of neuroimaging standards are not uniform, the results also have some bias. Therefore, to better understand the potential mechanism of acupuncture on migraine, a large sample, multicenter controlled trial is needed for further study. In addition, the application of machine learning methods in neuroimaging studies could help predict the efficacy of acupuncture and screen migraine patients suitable for acupuncture treatment.
Outcome and clinical features in juvenile myasthenia gravis: A systematic review and meta-analysis
Authors: Lin Yangtao , Kuang Qianjin , Li Hongjin , Liang Bo , Lu Jiaxin , Jiang Qilong , Yang Xiaojun
Published: March 2023

Background

Juvenile myasthenia gravis (JMG) is a rare autoimmune disease that has so far only been described in small cohort studies. We defined the clinical characteristics, management, and outcomes of JMG patients over the past 22 years.

Methods

A search of PubMed, EMBASE, and web of science (1/2000–2/2022) identified all English language and human studies of JMG. The population was patients diagnosed with JMG. Outcomes included the history of myasthenic crisis, autoimmune comorbidity, mortality, and treatment outcome. Data extraction was performed by independent reviewers. And we performed a pooled reanalysis of all published data in the included studies and compared with other studies of adult cohorts.

Results

We identified 11 articles describing 1,109 patients diagnosed between 2006 and 2021. JMG occurred in 60.4% of female patients. The mean age at presentation was 7.38 years old, and 60.6% of the patients had ocular symptoms as the first clinical manifestation. The most common initial presentation was ptosis, which occurred in 77.7% patients. AchR-Ab positive accounted for 78.7%. 641 patients received thymus examination, found to have thymic hyperplasia in 64.9% and thymoma in 2.2%. Autoimmune comorbidity was found in 13.6% and the most common one is thyroid disease (61.5%). First-line therapy, including pyridostigmine and steroids, was initiated in 97.8 and 68.6%, respectively. Six patients resolved spontaneously without treatment. Thymectomy was performed in 45.6%. 10.6% of patients had a history of myasthenic crisis. Completely stable remission was achieved in 23.7% and mortality was reported in 2 studies, which reported 8 deaths.

Conclusion

JMG is a rare disease with a relatively benign course, and differs from adult MG in some clinical features. The treatment regimen guideline for children is still not well-established. There is a need for prospective studies to properly evaluate treatment regimes.
Maximum likelihood-based estimation of diffusion coefficient is quick and reliable method for analyzing estradiol actions on surface receptor movements
Authors: Makkai Geza , Abraham Istvan M. , Barabas Klaudia , Godo Soma , Ernszt David , Kovacs Tamas , Kovacs Gergely , Szocs Szilard , Janosi Tibor Z.
Published: March 2023

The rapid effects of estradiol on membrane receptors are in the focus of the estradiol research field, however, the molecular mechanisms of these non-classical estradiol actions are poorly understood. Since the lateral diffusion of membrane receptors is an important indicator of their function, a deeper understanding of the underlying mechanisms of non-classical estradiol actions can be achieved by investigating receptor dynamics. Diffusion coefficient is a crucial and widely used parameter to characterize the movement of receptors in the cell membrane. The aim of this study was to investigate the differences between maximum likelihood-based estimation (MLE) and mean square displacement (MSD) based calculation of diffusion coefficients. In this work we applied both MSD and MLE to calculate diffusion coefficients. Single particle trajectories were extracted from simulation as well as from α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor tracking in live estradiol-treated differentiated PC12 (dPC12) cells. The comparison of the obtained diffusion coefficients revealed the superiority of MLE over the generally used MSD analysis. Our results suggest the use of the MLE of diffusion coefficients because as it has a better performance, especially for large localization errors or slow receptor movements.
Adamantanes for the treatment of neurodegenerative diseases in the presence of SARS-CoV-2
Authors: Butterworth Roger F.
Published: March 2023

Advent of the acute respiratory coronavirus SARS-CoV-2 has resulted in the search for novel antiviral agents and in the repurposing of existing agents with demonstrated efficacy against other known coronaviruses in the search for an agent with antiviral activity for use during the COVID-19 pandemic. Adamantanes including amantadine, rimantadine, and memantine have well-established benefit in the treatment of neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD) and fatigue related to Multiple sclerosis (MS) all of which are known comorbidities related to COVID-19 Moreover, results of basic pharmacological studies both in vitro and in vivo reveal that amantadine has the potential to inhibit SARS-CoV-2 via down-regulation of host-cell proteases resulting in impaired viral genome release into the host cell and via amantadine’s property as an NMDA receptor antagonist resulting in the prevention of the acute lung injury and respiratory distress that is characteristic of COVID-19. Cases suggestive of COVID-19 prophylaxis have been reported in patients with PD or MS or severe cognitive impairment treated in all cases for several months with an adamantane [amantadine or memantine] who were subsequently infected with SARS-CoV-2 confirmed by RT-PCR, and, in all cases, no signs of infectious disease were encountered. Amantadine is effective for the treatment of fatigue in MS and for the neurological complications of Traumatic Brain Injury (TBI).
Pre-stimulus beta power varies as a function of auditory-motor synchronization and temporal predictability
Authors: Schmidt-Kassow Maren , White Timothy-Niccolo , Abel Cornelius , Kaiser Jochen
Published: March 2023

Introduction

Auditory-motor interactions can support the preparation for expected sensory input. We investigated the periodic modulation of beta activity in the electroencephalogram to assess the role of active auditory-motor synchronization. Pre-stimulus beta activity (13–30 Hz) has been interpreted as a neural signature of the preparation for expected sensory input.

Methods

In the current study, participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either rhythmically (at 1 Hz) or arrhythmically with variable intervals. In addition to the pedaling conditions with rhythmic (auditory-motor synchronization, AMS) or arrhythmic stimulation, a self-generated stimulus condition was used in which tones were presented in sync with the participants’ spontaneous pedaling. This condition served to explore whether sensory predictions are driven primarily by the auditory or by the motor system.

Results

Pre-stimulus beta power increased for rhythmic compared to arrhythmic stimulus presentation in both sitting and pedaling conditions but was strongest in the AMS condition. Furthermore, beta power in the AMS condition correlated with motor performance, i.e., the better participants synchronized with the rhythmic stimulus sequence, the higher was pre-stimulus beta power. Additionally, beta power was increased for the self-generated stimulus condition compared with arrhythmic pedaling, but there was no difference between the self-generated and the AMS condition.

Discussion

The current data pattern indicates that pre-stimulus beta power is not limited to neuronal entrainment (i.e., periodic stimulus presentation) but represents a more general correlate of temporal anticipation. Its association with the precision of AMS supports the role of active behavior for auditory predictions.
Examination of sleep in relation to dietary and lifestyle behaviors during Ramadan: A multi-national study using structural equation modeling among 24,500 adults amid COVID-19
Authors: Khan Moien A. B. , BaHammam Ahmed S. , Amanatullah Asma , Obaideen Khaled , Arora Teresa , Ali Habiba , Cheikh Ismail Leila , Abdelrahim Dana N. , Al-Houqani Mohammed , Allaham Kholoud , Abdalrazeq Rand , Aloweiwi Wahid Sharif , Mim Somayea Sultana , Mektebi Ammar , Amiri Sohrab , Sulaiman Sahabi Kabir , Javaid Syed Fahad , Hawlader Mohammad Delwer Hossain , Tsiga-Ahmed Fatimah Isma’il , Elbarazi Iffat , Manggabarani Saskiyanto , Hunde Gamechu Atomsa , Chelli Sabrina , Sotoudeh Mitra , Faris MoezAlIslam Ezzat ,   Ramadan Intermittent Fasting Collaborators
Published: March 2023

Background

Of around 2 billion Muslims worldwide, approximately 1.5 billion observe Ramadan fasting (RF) month. Those that observe RF have diverse cultural, ethnic, social, and economic backgrounds and are distributed over a wide geographical area. Sleep is known to be significantly altered during the month of Ramadan, which has a profound impact on human health. Moreover, sleep is closely connected to dietary and lifestyle behaviors.

Methods

This cross-sectional study collected data using a structured, self-administered electronic questionnaire that was translated into 13 languages and disseminated to Muslim populations across 27 countries. The questionnaire assessed dietary and lifestyle factors as independent variables, and three sleep parameters (quality, duration, and disturbance) as dependent variables. We performed structural equation modeling (SEM) to examine how dietary and lifestyle factors affected these sleep parameters.

Results

In total, 24,541 adults were enrolled in this study. SEM analysis revealed that during RF, optimum sleep duration (7–9 h) was significantly associated with sufficient physical activity (PA) and consuming plant-based proteins. In addition, smoking was significantly associated with greater sleep disturbance and lower sleep quality. Participants that consumed vegetables, fruits, dates, and plant-based proteins reported better sleep quality. Infrequent consumption of delivered food and infrequent screen time were also associated with better sleep quality. Conflicting results were found regarding the impact of dining at home versus dining out on the three sleep parameters.

Conclusion

Increasing the intake of fruits, vegetables, and plant-based proteins are important factors that could help improve healthy sleep for those observing RF. In addition, regular PA and avoiding smoking may contribute to improving sleep during RF.
Reliability and validity of the Chinese version of the Sakata Eating Behavior Scale short form and preliminary analysis of the factors related to the score of the scale
Authors: Ge Pu , Wang Xinpei , Gao Siying , Liu Jiaxin , Niu Yuyao , Yan Mengyao , Fan Siyuan , Li Qiyu , Zhang Jinzi , Sun Xiaonan , Wang Fei , Sun Yike , Yu Wenli , Sun Xinying , Yu Lian , Wu Yibo
Published: March 2023

Background

The obesity rate in the Chinese population is increasing and there is a lack of short and reliable scales for measuring obesity-related eating behavior in China. The EBS-SF (Sakata Eating Behavior Scale short form) has only 7 entries and has shown good reliability in studies such as those in Japan.

Objective

To translate the EBS-SF into Chinese, check its reliability, validity and explore the related factors.

Method

The EBS-SF was translated into Chinese. 3,440 residents were investigated and 34 respondents were retested. Item analysis and reliability and validity tests were carried out. Personality characteristics, family health status and depression were investigated using the BFI-10, FHS-SF and PHQ-9 to investigate the factors associated with EBS-SF. The t-test, ANOVA and Pearson correlation was used to explore the related factors of its scores.

Result

Among 3,440 residents, 1,748 (50.81%) were male and 1,692 (49.19%) were female; 1,373 (39.91%) were aged 36–50 years. All 7 items were qualified in the item analysis. As for reliability, the Cronbach's α was 0.870, the split-half reliability was 0.830, the test-retest correlation coefficient was 0.868. As for the structural validity, the standardized factor loadings were above 0.50, χ2 / df = 2.081,GFI = 0.999; NFI = 0.999; RFI = 0.996; RMSEA = 0.018, all qualified. The characteristics, personality, family health and depression were correlated with the score of the Chinese version of EBS short form.

Conclusion

The structural validity and reliability of the Chinese version of the EBS-SF are good and it can be used as a measurement tool to evaluate the eating behavior of Chinese. The scores of the EBS-SF may be related to the sociological characteristics, personality, family health, and depression status.
The association of Wnt-signalling and EMT markers with clinical characteristics in women with endometrial cancer
Authors: Ledinek Živa , Sobočan Monika , Sisinger Damjan , Hojnik Marko , Büdefeld Tomaž , Potočnik Uroš , Knez Jure
Published: March 2023

Endometrial cancer is the most common gynecologic malignancy in the developed world. Risk stratification and treatment approaches are changing due to better understanding of tumor biology. Upregulated Wnt signaling plays an important role in cancer initiation and progression with promising potential for development of specific Wnt inhibitor therapy. One of the ways in which Wnt signaling contributes to progression of cancer, is by activating epithelial-to-mesenchymal transition (EMT) in tumor cells, causing the expression of mesenchymal markers, and enabling tumor cells to dissociate and migrate. This study analyzed the expression of Wnt signaling and EMT markers in endometrial cancer. Wnt signaling and EMT markers were significantly correlated with hormone receptors status in EC, but not with other clinico-pathological characteristics. Expression of Wnt antagonist, Dkk1 was significantly different between the ESGO-ESTRO-ESP patient risk assessment categories using integrated molecular risk assessment.
PSGL-1 is a novel tumor microenvironment prognostic biomarker with cervical high-grade squamous lesions and more
Authors: Lin Yingying , Huang Shan , Qi Yuanjie , Xie Li , Jiang Junying , Li Hua , Chen Zhiwei
Published: March 2023

Background

Macrophages secrete many cytokines and chemokines, which can provoke either an anti-tumor or pro-tumor immune response. P-selectin glycoprotein ligand-1 (PSGL-1) is expressed in macrophages and plays a vital role in synergizing for a more robust anti-tumor response. However, there are few studies about PSGL-1 expression status and clinical value of biological function in cervical cancer.

Methods

In this study, 565 participants were enrolled. PSGL-1 mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between PSGL-1 and cervical intraepithelial neoplasia in two grades and more (CIN2+) was analyzed, and the optimal cut-off values of PSGL-1 to predict CIN2+ were calculated. In addition, the clinical significance of PSGL-1 in cervical cancer was determined by Kaplan-Meier Cox regression based on the database.

Results

The mean PSGL-1 increased significantly with cervical lesion development, especially compared with CIN2+ (p<0.05). Moreover, the expression of PSGL-1 increased significantly in HPV-16/18 positive and HPV-18 positive, but not in HPV-16 positive and other HR-HPV positive. And then, it demonstrated that the area under the receiver operating characteristic curve (AUC) of PSGL-1 was 0.820, and an optimal cut-off 0.245. Furthermore, the PSGL-1 had the highest odds ratio and highest OR (OR= 8.707; 95% CI (.371-19.321)) for the detection of CIN 2+. In addition, our result also indicated that higher PSGL-1 expression was significantly related to a better prognosis in cervical cancer due to immune cell infiltration.

Conclusions

PSGL-1≥0.245 in cervical cytology specimens is a new auxiliary biomarker of CIN2+, and it may be a promising prognosis predictor and potential immunotherapy target linked with immune infiltration of cervical cancer.
Exploring the components and mechanism of Solanum nigrum L. for colon cancer treatment based on network pharmacology and molecular docking
Authors: Chen Jin-Fang , Wu Shi-Wei , Shi Zi-Man , Qu Yan-Jie , Ding Min-Rui , Hu Bing
Published: March 2023

Background

Solanum nigrum L. (SNL) (Longkui) is a Chinese herb that can be used to treat colon cancer. The present study explored the components and mechanisms of SNL in treating colon cancer by using network pharmacology and molecular docking.

Methods

The components of SNL were collected from the TCMSP, ETCM, HERB, and NPASS databases. Meanwhile, the target proteins of these ingredients were collected/predicted by the TCMSP, SEA, SwissTargetPrediction, and the STITCH databases colon cancer-related target genes were identified from TCGA and GTEx databases. The interaction networks were established via Cytoscape 3.7.2. Gene Ontology and KEGG pathways were enriched by using the David 6.8 online tool. Finally, the binding of key components and targets was verified by molecular docking, and the cellular thermal shift assay (CETSA) was used to detect the efficiency of apigenin and kaempferol binding to the AURKB protein in CT26 cells.

Results

A total of 37 SNL components, 796 SNL targets, 5,356 colon cancer genes, and 241 shared targets of SNL and colon cancer were identified. A total of 43 key targets were obtained through topology analysis. These key targets are involved in multiple biological processes, such as signal transduction and response to drug and protein phosphorylation. At the same time, 104 signaling pathways, such as pathways in cancer, human cytomegalovirus infection, and PI3K-Akt signaling pathway, are also involved. The binding of the four key components (i.e., quercetin, apigenin, kaempferol, and luteolin) and the key targets was verified by molecular docking. The CETSA results showed that apigenin and kaempferol were able to bind to the AURKB protein to exert anti-CRC effects.

Conclusions

Quercetin, apigenin, kaempferol, and luteolin are the main components of SNL in treating colon cancer. SNL regulates multiple bioprocesses via signaling pathways, such as pathways in cancer, PI3K-Akt, and cell cycle signaling pathways.
The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives
Authors: Gargiulo Ernesto , Giordano Mirta , Niemann Carsten U. , Moussay Etienne , Paggetti Jérôme , Morande Pablo Elías
Published: March 2023

Hairy cell leukemia (HCL) is an incurable, rare lymphoproliferative hematological malignancy of mature B cAlthough first line therapy with purine analogues leads to positive results, almost half of HCL patients relapse after 5-10 years, and standard treatment may not be an option due to intolerance or refractoriness. Proliferation and survival of HCL cells is regulated by surrounding accessory cells and soluble signals present in the tumor microenvironment, which actively contributes to disease progression. In vitro studies show that different therapeutic approaches tested in HCL impact the tumor microenvironment, and that this milieu offers a protection affecting treatment efficacy. Herein we explore the effects of the tumor microenvironment to different approved and experimental therapeutic options for HCL. Dissecting the complex interactions between leukemia cells and their milieu will be essential to develop new targeted therapies for HCL patients.
Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
Authors: Li Kehan , Liu Hejing , Lin Yibin , Gu Liang , Xiang Xinli , Zhu Xueqiong
Published: March 2023

Purpose

Aimed to identify the anti-uterine corpus endometrial carcinoma (UCEC) function and characterize the mechanism of quercetin in the treatment of patients infected with COVID-19 via integrated in silico analysis.

Methods

The Cancer Genome Atlas and Genotype Tissue Expression databases were applied to obtain differentially expressed genes of UCEC and non-tumor tissue. Several in silico methods such as network pharmacology, functional enrichment analysis, Cox regression analyses, somatic mutation analysis, immune infiltration and molecular docking were used to investigate and analysis the biological targets, functions and mechanisms of anti-UCEC/COVID-19 of quercetin. Multiple methods such as CCK8 assay, Transwell assay and western blotting were performed to test proliferation, migration, and protein level of UCEC (HEC-1 and Ishikawa) cells.

Results

Functional analysis disclosed that quercetin against UCEC/COVID-19 mainly by ‘biological regulation’, ‘response to stimulus’, and ‘regulation of cellular process’. Then, regression analyses indicated that 9 prognostic genes (including ANPEP, OAS1, SCGB1A1, HLA‐A, NPPB, FGB, CCL2, TLR4, and SERPINE1) might play important roles in quercetin for treating UCEC/COVID-19. Molecular docking analysis revealed that the protein products of 9 prognostic genes were the important anti-UCEC/COVID-19 biological targets of quercetin. Meanwhile, the proliferation and migration of UCEC cells were inhibited by quercetin. Moreover, after treatment with quercetin, the protein level of ubiquitination-related gene ISG15 was decreased in UCEC cells in vitro.

Conclusions

Taken together, this study provides new treatment option for UCEC patients infected with COVID-19. Quercetin may work by reducing the expression of ISG15 and participating in ubiquitination-related pathways.
Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury
Authors: Yan Yujie , Wu Leilei , Li Xuefei , Zhao Lan , Xu Yaping
Published: March 2023

Radiation-induced lung injury (RILI) including radiation-induced pneumonitis and radiation-induced pulmonary fibrosis is a side effect of radiotherapy for thoracic tumors. Azithromycin is a macrolide with immunomodulatory properties and anti-inflammatory effects. The immunopathology of RILI that results from irradiation is robust pro-inflammatory responses with high levels of chemokine and cytokine expression. In some patients, pulmonary interstitial fibrosis results usually due to an overactive immune response. Growing clinical studies recently proposed that the anti-inflammatory and immunomodulatory effects of azithromycin may benefit patients with acute lung injury. It has been shown potential benefits for patients with RILI in preclinical studies. Azithromycin has a variety of immunomodulatory effect to improve the process of disease, including inhibition of pro-inflammatory cytokines production participating in the regulatory function of macrophages, changes in autophagy, and inhibition of neutrophil influx. We review the published evidence of mechanisms of azithromycin, and focus on the potential effect of azithromycin on the immune response to RILI.
Involvement of acid sensing ion channel (ASIC)-3 in an acute urinary bladder-colon cross sensitization model in rodent
Authors: Atmani Karim , Meleine Mathieu , Langlois Ludovic , Coëffier Moïse , Brumovsky Pablo , Leroi Anne-Marie , Gourcerol Guillaume
Published: March 2023

Introduction

Irritable bowel syndrome and bladder pain syndrome are both characterized by pain in response to organ distension. Epidemiologic studies showed that these two syndromes are often overlapped. Such overlap may be due to sharing of common extrinsic innervations between the colorectum and the urinary bladder, where cross-sensitization of the urinary bladder and the colon would occur in response to mechanical distension of either organ. The aim of this project was to develop and characterize a rodent model of urinary bladder-colon sensitization and to assess the role of the acid sensing ion channel (ASIC)-3.

Methods

Double retrograde labelling was performed to identify extrinsic primary afferent neurons innervating both the colon (Fluororuby) and urinary bladder (Fluorogold) in the L6-S1 dorsal root ganglia (DRG) in Sprague Dawley rats. The phenotype of the colon/urinary bladder co-innervating primary afferent neurons was assessed using immunohistochemistry directed against ASIC-3. Cross-organ sensitization was induced in Sprague Dawley rats by using an echography-guided intravesical administration of acetic acid (0.75%) under brief isoflurane anesthesia. Colonic sensitivity was assessed in conscious rats by measuring abdominal contraction during isobaric colorectal distension (CRD). Measurement of urinary bladder and colonic paracellular permeabilities and tissue myeloperoxidase assay were performed. The involvement of ASIC-3 was assessed by use of S1 intrathecal administration of the ASIC-3 blocker, APETx2 (2.2 µM).

Results

Immunohistochemistry showed that 73.1% of extrinsic primary afferent neurons co-innervating the colon and the urinary bladder express ASIC-3. By contrast, extrinsic primary afferent neurons innervating the colon only or the urinary bladder only were positive for ASIC-3 in 39.3% and 42.6%, respectively. Echography-guided intravesical administration of acetic acid resulted in colonic hypersensitivity to colorectal distension. This effect started 1 h post-injection and lasted up to 24 h, and was not longer seen after 3 days after injection. No colonic hyperpermeability and no difference in urinary bladder and colon MPO activity was observed between control and acetic acid-treated rats. Colonic sensitization by intravesical acetic acid administration was prevented by S1 intrathecal administration of APETx2.

Conclusion

We developed an acute pelvic cross-organ sensitization model in conscious rat. In this model, cross-organ sensitization is likely to involve S1-L6 extrinsic primary afferents co-innervating the colon and urinary bladder through an ASIC-3 pathway.
Case Report: Selexipag in pediatric pulmonary hypertension: Initiation, transition, and titration
Authors: Faircloth Jenna M. , Bhatt Neelam D. , Chartan Corey A. , Coleman Ryan D. , Villafranco Natalie , Ruiz Fadel E. , Morales-Demori Raysa , Whalen Elise , Ely Erin , Fombin Rozmeen , Varghese Nidhy P.
Published: March 2023

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited and selexipag is not FDA-approved for use in the pediatric pulmonary hypertension population, many US pediatric centers are expanding the use of this therapy to this younger population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children under 10 years of age, between 10 and 30 kg. Seven patients were initiated on selexipag therapy including de novo initiation and transition from intravenous treprostinil to oral selexipag. All patients were on stable background therapy with phosphodiesterase-5 inhibitor and endothelin receptor antagonist therapies at baseline. All patients reached their planned goal selexipag dose during admission without the need for changes to the titration schedule and without hemodynamic deterioration. In our experience, oral selexipag is safe and well-tolerated in young pediatric patients with pulmonary hypertension. Based on our favorable experience, we developed an institution-specific selexipag process algorithm for continued successful use in the pediatric population.
Pediatric brain tumors: A neuropathologist's approach to the integrated diagnosis
Authors: Viaene Angela N.
Published: March 2023

The classification of tumors of the central nervous system (CNS) is a rapidly evolving field. While tumors were historically classified on the basis of morphology, the recent integration of molecular information has greatly refined this process. In some instances, molecular alterations provide significant prognostic implications beyond what can be ascertained by morphologic examination alone. Additionally, tumors may harbor molecular alterations that provide a therapeutic target. Pediatric CNS tumors, in particular, rely heavily on the integration of molecular data with histologic, clinical, and radiographic features to reach the most accurate diagnosis. This review aims to provide insight into a neuropathologist’s approach to the clinical workup of pediatric brain tumors with an ultimate goal of reaching an integrated diagnosis that provides the most accurate classification and informs prognosis and therapy selection. The primary focus will center on how histology and molecular findings are used in combination with clinical and radiographic information to reach a final, integrated diagnosis.
Antiretroviral drugs efavirenz, dolutegravir and bictegravir dysregulate blood-brain barrier integrity and function
Authors: Huang Chang , Hoque Tozammel , Bendayan Reina
Published: March 2023

The implementation of combined antiretroviral therapy (cART) significantly reduces the mortality associated with human immunodeficiency virus (HIV) infection. However, complications such as HIV-associated neurocognitive disorders (HAND) remain a major health concern. We hypothesized that the toxicity of antiretroviral drugs (ARVs) may contribute to the pathogenesis of HAND in addition to cerebral viral infection. To address this question, we evaluated the impact of HIV integrase strand transfer inhibitors (dolutegravir and bictegravir), and a non-nucleoside reverse transcriptase inhibitor (efavirenz) on the integrity and permeability of various human and mouse blood-brain barrier (BBB) models, in vitro, ex vivo and in vivo. We observed a significant downregulation of tight junction proteins (TJP1/Tjp1, OCLN/Ocln and CLDN5/Cldn5), upregulation of proinflammatory cytokines (IL6/Il6, IL8/Il8, IL1β/Il1β) and NOS2/Nos2, and alteration of membrane-associated transporters (ABCB1/Abcb1a, ABCG2/Abcg2 and SLC2A1/Slc2a1) mRNA expression, in vitro, in human (hCMEC/D3) and primary cultures of mouse microvascular endothelial cells, and ex vivo in isolated mouse brain capillaries treated with efavirenz, dolutegravir, and/or bictegravir. We also observed a significant increase in BBB permeability in vivo following treatment with the selected ARVs in mice applying NaF permeability assay. Taken together, these results suggest that clinically recommended integrase strand transfer inhibitors such as dolutegravir may exacerbate HIV-associated cerebrovascular pathology, which may contribute to the associated short-term neuropsychiatric side effects and the high incidence of mild forms of HAND reported in the clinical setting.