bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of ponicidin on CFA-induced chronic inflammatory pain and its mechanism based on network pharmacology and molecular docking
Authors: Wang Peng , Jiang Huiyi , Yao Jinzhong , He Guangting , Tao Tao , Qin Zaisheng 
Published: February 2025

PurposeInflammation is a frequent precursor to the development of chronic pain. Ponicidin, a compound derived from traditional Chinese medicine, possesses immunomodulatory and anti-inflammatory properties. However, whether ponicidin mitigates inflammatory pain through its anti-inflammatory effects and potential target molecules remains to be further explored. In this study, we investigated the analgesic effects of ponicidin in a mouse model of Complete Freund's Adjuvant (CFA)—induced inflammatory pain and employed network pharmacology to predict the potential therapeutic targets of ponicidin for pain treatment.MethodsInitially, we established a mouse model of inflammatory pain induced by Complete Freund's Adjuvant (CFA). Following the establishment of the model, the analgesic effects of ponicidin were assessed using behavioral tests, and further validation was conducted through hematoxylin and eosin (H&amp;E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence methods. Subsequently, we analyzed the potential analgesic targets of ponicidin using network pharmacology approaches and molecular docking.ResultsIn this study, we observed that ponicidin has a significant alleviating effect on CFA-induced inflammatory pain. Our results suggest that ponicidin may alleviate inflammatory pain by reducing inflammatory responses in the spinal cord and hind paw of CFA model mice. Furthermore, we found that ponicidin can mitigate the activation of macrophages in the subcutaneous tissue of the hind paw and microglia in the dorsal horn of the spinal cord. Network pharmacology analysis suggests that ponicidin may exert its analgesic effects through a multi-target, multi-pathway mechanism. Key transcription factors such as nuclear factor NF-κB p105 subunit (NFKB1), RELA, SP1, signal transducer and activator of transcription 3 (STAT3), and repressor element 1 silencing transcription factor (REST) may be involved in the underlying mechanisms of ponicidin's analgesic action. Through molecular docking and experimental validation, we have identified toll-like receptor 4 (TLR4) and hypoxia-inducible factor 1-alpha (HIF1A) as key targets of ponicidin's analgesic effects.ConclusionsPonicidin alleviates inflammatory pain by reducing inflammatory responses in the spinal cord and hind paw of the CFA model mice. TLR4 and HIF1A may as key targets for the analgesic effects of ponicidin.
The effects of cognitive-motor multitasking demands on the quality of chest compressions in CPR—A randomized controlled trial
Authors: Hirsch Patricia , Pears Kim , Klasen Martin , Kiefer Christoph , Koch Iring , Sopka Saša 
Published: February 2025

BackgroundIn standard cardiopulmonary resuscitation (CPR), rescuers switch between ventilation and chest compressions. We examined the effect of this task-switching requirement on chest-compression quality to gain insights into the cognitive mechanisms underlying performance in standard CPR. Understanding these mechanisms can help in the development of evidence-based practical implications and cognitive aids for CPR.MethodsA total of 300 first-year medical and dentistry students (212 females, 20.2 ± 4.4 years) participated in this randomized controlled trial. They received either a CPR training comprising both chest compressions and ventilation (standard CPR) or a CPR training comprising chest compressions only (chest-compression-only CPR). Chest-compression quality (compression depth and rate) was measured via a resuscitation manikin and analyzed using linear mixed models and linear trend analyses.ResultsOverall, chest-compression quality did not differ across standard CPR and chest-compression-only CPR. However, in standard CPR, compression quality was better after ventilation than before ventilation. Importantly, ventilation impaired the quality of the compressions executed immediately after ventilation, but the quality increased with each compression after ventilation, resulting in a better chest-compression quality after ventilation than before it.ConclusionsThis study suggests that ventilation acts as a break, improving physical capability, which in turn enhances compressions after ventilation. However, at the same time, ventilation causes a task switch which increases cognitive demands and impairs chest-compression quality immediately after ventilation. Considering the negative effect of the task-switching demand on chest-compression quality, it is useful to develop cognitive aids for professional medical care. Such cognitive aids can signal an upcoming switch to ventilation, thereby reducing the multitasking load in terms of reduced monitoring demands with respect to the number of chest compressions that have already been executed.
Oral administration of glycyrrhizic acid with intramuscular injection of foot-and-mouth disease vaccine enhances the adaptive immune system
Authors: Shin Seokwon , Kim Hyeong Won , Ko Mi-Kyeong , Park So Hui , Park Jong-Hyeon , Kim Su-Mi , Lee Min Ja 
Published: February 2025

BackgroundCommercial foot-and-mouth disease (FMD) vaccines have several drawbacks, including a short duration of the immune response after vaccination and local adverse reactions at the vaccination site. Therefore, we developed a new vaccination strategy that simultaneously improves the health status of the host and stimulates systemic immunity by combining the oral administration of glycyrrhizic acid (GA) and intramuscular injection of the FMD vaccine.MethodsWe evaluated the efficacy of the oral immune enhancer GA in conjunction with an intramuscular injection of the FMD vaccine. After vaccination, the experimental (mice) and target animals (pigs) were orally administered GA daily for 4 weeks and once a week for the next 4 weeks. Subsequently, we evaluated safety using various biochemical serum assays, the efficacy of inducing immune responses using serological assays, and the expression of genes related to systemic immunity induction.ResultsOral administration of GA in combination with an intramuscular injection of the FMD vaccine enhanced early, mid-term, and long-term immunity in experimental and target animals. We also confirmed that this co-administration increased the expression of secretory IgA (sIgA), an important indicator of mucosal immunity. Additionally, significant gene elevations in systemic immune markers along with T helper (Th) immune responses were observed.ConclusionThese findings suggest that combining the oral administration of GA with the intramuscular injection of an inactivated FMD vaccine can induce a potent and sustained immune response and stimulate the systemic immune system by promoting sIgA and cytokine gene expression. Our research can be used to enhance the efficacy of existing commercial vaccines as well as control other animal diseases by improving the host’s immune system.
Impact of the COVID-19 pandemic on the mental and physical wellbeing of patients with motor neuron disease and other neuromuscular disease
Authors: Mazumder Srestha , Carroll Antonia S. , Timmins Hannah C. , Kiernan Matthew C. , Mahoney Colin J. 
Published: February 2025

Background and aimsDuring the COVID-19 pandemic, vulnerable populations faced worsening mental and physical well-being due to limited access to support systems and diverted health resources during lockdowns. Individuals with chronic neurological disorders including motor neuron disease (MND), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN) were at considerable risk of severe COVID-19 symptoms. The present study aimed to examine the psychological and physical impact of lockdowns on individuals with MND and other chronic neuromuscular disorders (non-MND).MethodsOnline surveys were distributed to 58 patients, with information prospectively collected to capture demographics, COVID-19 concerns, resilience, loneliness, anxiety, and depression using validated measures. Disease severity and physical activity levels were also assessed. Data was analysed using Mann–Whitney U and Chi-square tests.ResultsMND patients consistently showed resilience regardless of their impairment level. In further support, those with non-MND conditions reported greater concern for their mental well-being and experienced significantly more loneliness than MND patients (p = 0.005). Moderately to highly impaired non-MND patients experienced higher levels of loneliness (p = 0.024), anxiety (p = 0.006), and depression (p &lt; 0.001) compared to similarly impaired MND patients.ConclusionThese results suggest that despite having a poorer prognosis, MND patients demonstrate resilience, possibly reflecting increased social and allied health support. Neurobehavioral differences may also contribute to differing illness beliefs and behaviours. In the event of future pandemic events, additional targeted social supports, recreational activities, and allied health interventions may have a greater impact in reducing distress for those with CIDP and MMN.
Quantitative magnetic resonance imaging parameters of lumbar paraspinal muscle impairment in myotonic dystrophy type 2 and their evolution with aging
Authors: Kokosova Viktoria , Krkoska Peter , Vlazna Daniela , Sladeckova Michaela , Dostal Marek , Kerkovsky Milos , Barusova Tamara , Ovesna Petra , Parmova Olesja , Matulova Katerina , Adamova Blanka 
Published: February 2025

IntroductionMuscle magnetic resonance imaging (MRI) is an emerging method in the diagnosis and monitoring of muscular dystrophies. This cross-sectional, comparative study aimed to evaluate quantitative MRI (qMRI) parameters of the lumbar paraspinal muscles (LPM) in myotonic dystrophy type 2 (DM2), to assess their relationship with functional examination, and to evaluate their evolution with aging.MethodsThe study enrolled 37 DM2 patients and 90 healthy volunteers (HV) who were matched based on physiological parameters to create 35 pairs. Utilizing a 6-point Dixon gradient echo sequence MRI, fat fraction (FF), total muscle volume, and functional muscle volume (FMV) of the LPM and psoas muscle (PS) were obtained. Using correlation coefficients and regression models, the relationship between MRI and the maximal isometric lumbar extensor muscle strength (MILEMS) and lumbar extensor muscle endurance (LEME), and their evolution with age, were assessed.ResultsLPM showed significantly higher FF in DM2 patients compared to HV (21.3% vs. 11.3%, p-value &lt;0.001). FMV of LPM correlated significantly with MILEMS (ρ = 0.5, p- value = 0.001) and FF with LEME (ρ = −0.49, p- value = 0.002) in DM2. No significant differences in the rate of deterioration in functional and morphological parameters of the LPM with age were observed between the two groups.ConclusionWe demonstrated morphological correlates of lumbar extensor muscle dysfunction in DM2 patients. The qMRI parameters of LPM correlated with functional parameters but could not be used either as a reliable biomarker of lumbar extensor muscle impairment or as a biomarker of disease progression.
Chemogenetic modulation of the rat locus coeruleus alters hippocampal noradrenaline release and modulates perforant path-evoked responses
Authors: Caestecker Sielke , Lescrauwaet Emma , Vonck Kristl , Sprengers Mathieu , Carrette Evelien , Boon Paul , Larsen Lars Emil , Raedt Robrecht 
Published: February 2025

IntroductionThe locus coeruleus (LC)—noradrenaline (NA) system plays a crucial role in modulating neuronal excitability and plasticity. In epilepsy, the LC-NA system plays an important role in regulating seizure thresholds and severity, with elevated NA release mediating the seizure-suppressing effects of vagus nerve stimulation (VNS). We investigated whether chemogenetic LC activation is able to increase hippocampal NA release and affect hippocampal electrophysiology in anesthetized rats.Methods22 male Sprague—Dawley rats were injected with the viral vector AAV9-hSyn-NE2m in the hippocampus to induce expression of the GRABNE2m biosensor to locally measure changes in extracellular NA. 15/22 rats were injected with the CAV2-PRSx8-hM3Dq hSyn-mCherry viral vector in the LC to express the excitatory DREADD hM3Dq, allowing LC activation with deschloroclozapine (DCZ), and 7/22 with CAV2-PRSx8-GtACR2 as a control. A perforant path stimulation electrode and a dentate gyrus (DG) recording electrode were implanted for local field potential (LFP) and evoked potential (EP) recording as well as a DG optical fiber for GRABNE2m fluorescence measurement.ResultsIn a significant number of rats (7/15) we found an increase in hippocampal NA release, field excitatory post synaptic potential (fEPSP) slope and population spike (PS) amplitude, indicating an increase in excitatory neurotransmission and neuronal output. 4/15 rats showed a decrease in NA release without changes in fEPSP slope or PS amplitude, and 4/15 showed no change in NA release.DiscussionThese findings indicate that chemogenetic activation of the LC-NA system can modulate hippocampal evoked responses, supporting further exploration of its role in health and disease, such as in epilepsy.
Plasma exosomal miRNA expression and gut microbiota dysbiosis are associated with cognitive impairment in Alzheimer’s disease
Authors: Lin Kaihao , Lin Wenxia , Guo Zhikai , Chen Cuihong , Chen Liang , Cai Xianbin 
Published: February 2025

IntroductionThe gut microbiota composition and the expression profiles of microRNAs (miRNAs) in the brain tissue, cerebrospinal fluid, and blood of patients with Alzheimer’s disease (AD) differ significantly from those with normal cognition function. The study aimed to initially explore the relationship between plasma exosomal microRNAs, gut microbiota, and cognitive impairment, providing insights into the pathogenesis and treatment of AD.MethodsThe study enrolled 8 participants with AD and 8 participants with normal cognition. The Mini-Mental State Examination (MMSE) was utilized to evaluate cognitive function. High-throughput sequencing was used to identify differentially expressed miRNAs in plasma exosomes, while metagenomic sequencing was employed to detect differences in the abundance of gut microbiota. Furthermore, the associations among them were analyzed.ResultsFour exosomal miRNAs and 14 microbiota taxa, which exhibited differential expression and abundance, respectively, in comparison between AD group and normal cognition group, were identified to be significantly associated with MMSE scores. Notably, the abundance of potential probiotics, including Faecalibacterium prausnitzii, Roseburia intestinalis and Roseburia inulinivorans, which was decreased in AD patients, exhibited positive correlations with specific exosomal miRNAs: Roseburia intestinalis correlated with miR-3120-3p and miR-6529-5p; Roseburia inulinivorans correlated with miR-3120-3p, miR-6529-5p and miR-124-3p; Faecalibacterium prausnitzii correlated with miR-3120-3p.DiscussionThe study revealed a close association among gut microbiota, plasma exosomal miRNAs, and cognitive impairment in AD, and suggested that specific components of gut microbiota and exosomal miRNAs may serve as potential biomarkers and therapeutic targets for AD on the microbiota-gut-brain axis.
Reference values for the appendicular lean muscle index in healthy young Saudi women: a nutritional perspective
Authors: Alhussain Maha H. , Alamro Samar A. , Alghannam Abdullah F. , Alabdullatif Rawan A. , Alkahtani Shaea 
Published: February 2025

BackgroundSarcopenia refers to the age-related decline in muscle function, including muscle strength and muscle mass. It can be diagnosed using the appendicular lean muscle index (ALMI) for specific populations. However, reference values for the ALMI in Saudi women are lacking.AimThis study aimed to determine the ALMI reference values in young Saudi women using bioelectrical impedance analysis (BIA). The relationship between ALM and dietary intake was also investigated.MethodsA total of 387 healthy young Saudi women, aged between 18 and 25 years, were included in this study. They were recruited through a convenience sampling method between October 2020 and June 2021. Body composition was assessed using BIA (Inbody 770). The ALMI was determined by calculating the sum of lean tissue in the arms and legs and dividing it by the height squared (ALM/h2). The cutoff value was calculated by deriving the −2 standard deviation (SD) value based on the participants’ data. A 24-h dietary recall was also conducted, and energy and macronutrient intakes were assessed.ResultsThe mean ALM/h2 was 5.63 ± 0.77 kg/m2, and the mean ALM/ht2, −2 SD value was 4.09 kg/m2 for the young Saudi reference group. There were significant positive correlations between ALM and protein (g/day) (r = 0.15; p &lt; 0.001), protein (%) (r = 0.16; p = 0.002), fiber (g/day) (r = 0.21; p &lt; 0.001), and cholesterol (mg/day) (r = 0.14; p = 0.007). However, the ALM showed a significant negative correlation with carbohydrates (%) (r = − 0.11; p = 0.03).ConclusionThese findings provide valuable reference values for evaluating ALM in patients with a variety of diseases that impact ALM. Furthermore, a cutoff value for low ALM may assist in the diagnosis of sarcopenia in Saudi women and enhance our understanding of the effects of total dietary nutrient intake on sarcopenia.
Differentiating pancreatic ductal adenocarcinoma and autoimmune pancreatitis using a machine learning model based on ultrasound clinical features
Authors: Zhang Lihua , Chen Xiang , Chen Zhikui , Chen Weiji , Zheng Jianmei , Zhuo Minling , Chen Xing 
Published: February 2025

PurposeThis study aimed to construct a differential diagnostic model to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDCA) using ultrasound clinical features and machine learning algorithms.MethodsRetrospective ultrasound clinical data of patients with AIP and PDCA from three different centers were used as the training cohort, external validation cohort 1, and external validation cohort 2. Feature selection was conducted via variance filtering and LASSO regression, followed by the construction of a random forest (RF) model. The hyperparameters were optimized in the training cohort, and the final model was evaluated in the external validation cohorts. The model’s performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the F1 score, accuracy, and area under curve(AUC). The clinical application value of the model was clarified through a comparison between humans and machines.ResultsAn RF model was constructed using six features: Ca 19-9 level, abdominal pain, jaundice, focal/diffuse-type AIP, blood flow signals, and morphology. In external validation cohort 1, the model’s sensitivity, specificity, PPV, NPV, F1 score, accuracy, and AUC were 86.0%, 80.0%, 81.0%, 86.0%, 84.0%, 83.0%, and 89.0%, respectively; in external validation cohort 2, these values were 72.0%, 94.0%, 93.0%, 77.0%, 81.0%, 83.0%, and 91.0%, respectively. The predictive performance of experienced radiologists using clinical information and ultrasound images demonstrated a sensitivity of 81%, specificity of 79%, PPV of 78%, NPV of 76%, F1 score of 80%, and accuracy of 80%. For radiologists with intermediate experience, the sensitivity was 75%, specificity was 74%, PPV was 73%, NPV was 76%, F1 score was 74%, and accuracy was 75%. less experienced radiologist had a sensitivity of 55%, specificity of 56%, PPV of 62%, NPV of 49%, F1 score of 58%, and accuracy of 55%.ConclusionThe RF model constructed using clinical ultrasound features achieved diagnostic levels comparable to those of experienced radiologists and can assist in differentiating AIP from PDCA, potentially guiding clinical practice.
Effects of Th1/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes
Authors: Cavallo Alessia , Camera Emanuela , Maiellaro Miriam , Bottillo Grazia , Mosca Sarah , Kovacs Daniela , Flori Enrica , Cardinali Giorgia 
Published: February 2025

IntroductionAbnormalities of keratinocyte differentiation and impairment of permeability barrier are features of inflammatory skin diseases driven by Th1/Th17 and Th2 immune response, such as psoriasis and atopic dermatitis. We aimed at identifying the signature of the Th1/Th17 and Th2 environments on keratinocytes, focusing on the expression of genes involved in the lipid metabolism and profiles of abundance of lipid metabolites.MethodsHuman immortalized keratinocytes in prodifferentiative conditions induced by increasing calcium concentration, and 3D epidermal equivalents were treated with mixtures either of TNF-α and IL-17A plus Th1-related cytokines (IL-1α, IL-6) or of Th2 cytokines (IL-4, IL-13). The expression of genes involved in epidermal differentiation and lipid metabolism was evaluated by RT-PCR at 2, 4 and 7 days of treatment. The protein levels of early and late keratinocyte differentiation markers were assessed. The lipid composition was investigated by GCMS and LCMS.ResultsBoth Th1/Th17 and Th2 cytokine mixtures changed the expression of genes involved in the metabolism of fatty acids (FAs), i.e., FAS, FADS2, SCD1, and ALOX12B. Th1/ Th17 downregulated the ELOVL3 gene, which is implicated in the FAs elongation, while the mRNA levels of ABCA12 and HMGCR, genes involved in lipids transport and cholesterol synthesis, respectively, were decreased with both cytokine mixtures. DEGS1 and DEGS2, key enzymes in the ceramide synthesis, were downregulated and upregulated in the Th1/Th17 and Th2 environments, respectively. The mRNA expression of CERS3, which synthesizes ceramides containing long chain FAs, was increased by Th1/Th17 cytokines. Both Th1/ Th17 and Th2 cytokine mixtures lowered the CERS6 mRNA levels in differentiated keratinocytes. Effects specific to Th1/Th17 or Th2 cytokines were observed on freely extractable cell lipids. Th1/Th17 cytokines significantly inhibited the high calcium-induced synthesis of phospholipids (PCs, PEs, SMs), and short-chain ceramides, while the synthesis of ceramides with medium to long carbon chains was upregulated. Th2 cytokines caused a generalized decrement of free FAs, including long-chain ones. In contrast to 2D cultures, the 3D epidermal equivalents allowed the identification of altered profiles of acyland hexosyl-ceramides.ConclusionThe different effects exerted by Th1/Th17 and Th2 cytokines support, at least in part, the features of lipid barrier alterations specific to psoriasis or atopic dermatitis.