bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactobacillus acidophilus inhibits the TNF-α-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-κB activation
Authors: Haque Mohammad , Kaminsky Lauren , Abdulqadir Raz , Engers Jessica , Kovtunov Evgeny , Rawat Manmeet , Al-Sadi Rana , Ma Thomas Y. 
Published: July 2024

BackgroundDefective intestinal epithelial tight junction (TJ), characterized by an increase in intestinal TJ permeability, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease (IBD). Tumor necrosis factor-α (TNF-α) is a key pro-inflammatory cytokine involved in the immunopathology of IBD and has been shown to cause an increase in intestinal epithelial TJ permeability. Although TNF-α antibodies and other biologics have been advanced for use in IBD treatment, these therapies are associated with severe side effects and have limited efficacy, and there is an urgent need for therapies with benign profiles and high therapeutic efficacy. Probiotic bacteria have beneficial effects and are generally safe and represent an important class of potential therapeutic agents in IBD. Lactobacillus acidophilus (LA) is one of the most used probiotics for wide-ranging health benefits, including in gastrointestinal, metabolic, and inflammatory disorders. A specific strain of LA, LA1, was recently demonstrated to have protective and therapeutic effects on the intestinal epithelial TJ barrier. However, the mechanisms of actions of LA1 remain largely unknown.MethodsThe primary aim of this study was to investigate microbial-epithelial interactions and novel signaling pathways that regulate the effect of LA1 on TNF-α-induced increase in intestinal epithelial TJ permeability, using cell culture and animal model systems.Results and ConclusionPre-treatment of filter-grown Caco-2 monolayers with LA1 prevented the TNF-α-induced increase in intestinal epithelial TJ permeability by inhibiting TNF-α-induced activation of NF-κB p50/p65 and myosin light chain kinase (MLCK) gene and kinase activity in a TLR-2-dependent manner. LA1 produced a TLR-2- and MyD88-dependent activation of NF-κB p50/p65 in immune cells; however, LA1, in intestinal cells, inhibited the NF-κB p50/p65 activation in a TLR-2-dependent but MyD88-independent manner. In addition, LA1 inhibition of NF-κB p50/p65 and MLCK gene was mediated by TLR-2 pathway activation of phosphatidylinositol 3-kinase (PI3K) and IKK-α phosphorylation. Our results demonstrated novel intracellular signaling pathways by which LA1/TLR-2 suppresses the TNF-α pathway activation of NF-κB p50/p65 in intestinal epithelial cells and protects against the TNF-α-induced increase in intestinal epithelial TJ permeability.
Immunological characteristics of a recombinant alphaherpesvirus with an envelope-embedded Cap protein of circovirus
Authors: Lu Chenhe , Li Haimin , Chen Wenjing , Li Hui , Ma Jiayu , Peng Peng , Yan Yan , Dong Weiren , Jin Yulan , Pan Shiyue , Shang Shaobin , Gu Jinyan , Zhou Jiyong 
Published: July 2024

IntroductionVariant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.MethodsWe reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.ResultsAn immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.ConclusionCollectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
Mechanistic insights into rumen function promotion through yeast culture (Saccharomyces cerevisiae) metabolites using in vitro and in vivo models
Authors: Chen Xue , Xiao Jun , Zhao Wanzhu , Li Yanan , Zhao Wei , Zhang Weigang , Xin Liang , Han Zhiyi , Wang Lanhui , Aschalew Natnael Demelash , Zhang Xuefeng , Wang Tao , Qin Guixin , Sun Zhe , Zhen Yuguo 
Published: July 2024

IntroductionYeast culture (YC) enhances ruminant performance, but its functional mechanism remains unclear because of the complex composition of YC and the uncertain substances affecting rumen fermentation. The objective of this study was to determine the composition of effective metabolites in YC by exploring its effects on rumen fermentation in vitro, growth and slaughter performance, serum index, rumen fermentation parameters, rumen microorganisms, and metabolites in lambs.MethodsIn Trial 1, various YCs were successfully produced, providing raw materials for identifying effective metabolites. The experiment was divided into 5 treatment groups with 5 replicates in each group: the control group (basal diet without additives) and YC groups were supplemented with 0.625‰ of four different yeast cultures, respectively (groups A, B, C, and D). Rumen fermentation parameters were determined at 3, 6, 12, and 24 h in vitro. A univariate regression model multiple factor associative effects index (MFAEI; y) was established to correlate the most influential factors on in vitro rumen fermentation with YC metabolites (x). This identified the metabolites promoting rumen fermentation and optimal YC substance levels. In Trial 2, metabolites in YC not positively correlated with MFAEI were excluded, and effective substances were combined with pure chemicals (M group). This experiment validated the effectiveness of YC metabolites in lamb production based on their impact on growth, slaughter performance, serum indices, rumen parameters, microorganisms, and metabolites. Thirty cross-generation rams (Small tail Han-yang ♀ × Australian white sheep ♂) with good body condition and similar body weight were divided into three treatment groups with 10 replicates in each group: control group, YC group, pure chemicals combination group (M group).ResultsGrowth performance and serum index were measured on days 30 and 60, and slaughter performance, rumen fermentation parameters, microorganisms, and metabolites were measured on day 60. The M group significantly increased the dressing percentage, and significantly decreased the GR values of lambs (p  &lt; 0.05). The concentration of growth hormone (GH), Cortisol, insulin (INS), and rumen VFA in the M group significantly increased (p &lt; 0.05).DiscussionThese experiments confirmed that YC or its screened effective metabolites positively impact lamb slaughter performance, rumen fermentation, and microbial metabolism.
Real-world use of imipenem/cilastatin/relebactam for the treatment of KPC-producing Klebsiella pneumoniae complex and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa infections: a single-center preliminary experience
Authors: Leanza Cristiana , Mascellino Maria Teresa , Volpicelli Lorenzo , Covino Sara , Falletta Antonio , Cancelli Francesca , Franchi Cristiana , Carnevalini Martina , Mastroianni Claudio M. , Oliva Alessandra 
Published: July 2024

IntroductionReal-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPC-Kp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described.MethodsAdult patients with KPC-Kp or DTR-PA infections who received ≥48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL.ResultsWe included 10 patients with different infections caused by DTR-PA (n = 4), KPC-Kp [n = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp (n = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilator-associated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported.DiscussionWe reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections.
Differently increased volumes of multiple brain areas in Npc1 mutant mice following various drug treatments
Authors: Antipova Veronica , Heimes Diana , Seidel Katharina , Schulz Jennifer , Schmitt Oliver , Holzmann Carsten , Rolfs Arndt , Bidmon Hans-Jürgen , González de San Román Martín Estibaliz , Huesgen Pitter F. , Amunts Katrin , Keiler Jonas , Hammer Niels , Witt Martin , Wree Andreas 
Published: July 2024

BackgroundNiemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of Npc1−/− displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. Npc1−/− mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of Npc1−/− mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced.MethodsIn order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods.ResultsIn the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated Npc1−/− mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures.DiscussionVolumes of brain areas of Npc1−/− mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in Npc1−/− mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.
Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors
Authors: Iijima Keiya , Fujii Hiroyuki , Suzuki Fumio , Murayama Kumiko , Goto Yu-ichi , Saito Yuko , Sano Terunori , Suzuki Hiroyoshi , Miyata Hajime , Kimura Yukio , Nakashima Takuma , Suzuki Hiromichi , Iwasaki Masaki , Sato Noriko 
Published: July 2024

IntroductionLow-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics.MethodsThis study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes.ResultsThree distinct neuroimaging groups were established: Group 1 had indistinct borders and iso T1-weighted and slightly high or high T2-weighted signal intensities without a diffuse mass effect, associated with 93.8% sensitivity and 100% specificity to BRAF V600E mutations; Group 2 exhibited sharp borders and very or slightly low T1-weighted and very high T2-weighted signal intensities with a diffuse mass effect and 100% sensitivity and specificity for FGFR1 mutations; and Group 3 displayed various characteristics. Histopathological diagnoses including diffuse low-grade glioma and ganglioglioma showed no clear association with genotypes. Notably, postoperative seizure-free rates were higher in Group 1 tumors (BRAF V600E) than in Group 2 tumors (FGFR1).DiscussionThese findings suggest that tumor genotype may be predicted by neuroimaging before surgery, providing insights for personalized treatment approaches.
Ischemic perfusion radiomics: assessing neurological impairment in acute ischemic stroke
Authors: Lu Jiaxi , Yassin Mazen M. , Guo Yingwei , Yang Yingjian , Cao Fengqiu , Fang Jiajing , Zaman Asim , Hassan Haseeb , Zeng Xueqiang , Miao Xiaoqiang , Yang Huihui , Cao Anbo , Huang Guangtao , Han Taiyu , Luo Yu , Kang Yan 
Published: July 2024

IntroductionAccurate neurological impairment assessment is crucial for the clinical treatment and prognosis of patients with acute ischemic stroke (AIS). However, the original perfusion parameters lack the deep information for characterizing neurological impairment, leading to difficulty in accurate assessment. Given the advantages of radiomics technology in feature representation, this technology should provide more information for characterizing neurological impairment. Therefore, with its rigorous methodology, this study offers practical implications for clinical diagnosis by exploring the role of ischemic perfusion radiomics features in assessing the degree of neurological impairment.MethodsThis study employs a meticulous methodology, starting with generating perfusion parameter maps through Dynamic Susceptibility Contrast-Perfusion Weighted Imaging (DSC-PWI) and determining ischemic regions based on these maps and a set threshold. Radiomics features are then extracted from the ischemic regions, and the t-test and least absolute shrinkage and selection operator (Lasso) algorithms are used to select the relevant features. Finally, the selected radiomics features and machine learning techniques are used to assess the degree of neurological impairment in AIS patients.ResultsThe results show that the proposed method outperforms the original perfusion parameters, radiomics features of the infarct and hypoxic regions, and their combinations, achieving an accuracy of 0.926, sensitivity of 0.923, specificity of 0.929, PPV of 0.923, NPV of 0.929, and AUC of 0.923, respectively.ConclusionThe proposed method effectively assesses the degree of neurological impairment in AIS patients, providing an objective auxiliary assessment tool for clinical diagnosis.
Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles (Microtus ochrogaster)
Authors: Nerio-Morales Lina K. , Boender Arjen J. , Young Larry J. , Lamprea Marisol R. , Smith Adam S. 
Published: July 2024

IntroductionThe social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (Microtus ochrogaster). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin. Here, we assessed the functional significance of OXTR in stress-induced social avoidance and the response of the MAPK signaling pathway in the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and basolateral amygdala (BLA) of female prairie voles.MethodsIn experiment 1, Sexually naïve adult female prairie voles were defeated for three consecutive days and tested a week after for social preference/avoidance (SPA) test. Control subjects were similarly handled without defeat conditioning. In experiment 2, sexually and stress naïve adult female prairie voles were bilaterally injected into the NAc, ACC, or the BLA with a CRISPR/Cas9 virus targeting the Oxtr coding sequence to induce OXTR knockdown. Two weeks post-surgery, subjects were tested for SPA behavior. Viral control groups were similarly handled but injected with a control virus. A subgroup of animals from each condition in both experiments were similarly treated and euthanized without being tested for SPA behavior. Brains were harvested for OXTR autoradiography, western blot analysis of MAPK proteins and quantification of local oxytocin content in the NAc, BLA, ACC, and PVN through ELISA.ResultsSocial defeat reduced OXTR binding in the NAc and affected MAPK pathway activity and oxytocin availability. These results were region-specific and sensitive to exposure to the SPA test. Additionally, OXTR knockdown in the NAc, ACC, and BLA induced social avoidance and decreased basal MAPK activity in the NAc. Finally, we found that OXTR knockdown in these regions was associated with less availability of oxytocin in the PVN.ConclusionDysregulation of the oxytocin system and MAPK signaling pathway in the NAc, ACC, and BLA are important in social behavior disruptions in female voles. This dysregulation could, therefore, play an important role in the etiology of SAD in women.
Association between nutrition-related indicators with the risk of chronic obstructive pulmonary disease and all-cause mortality in the elderly population: evidence from NHANES
Authors: Xu Yifeng , Yan Zhaoqi , Li Keke , Liu Liangji , Xu Lei 
Published: July 2024

BackgroundThis study aims to use six nutrition-related indicators to assess the relationship between nutritional status and the risk of COPD as well as the all-cause mortality rate, and to determine the most reliable predictive indicators.MethodsData from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2013 to 2018 were extracted. Nutritional status was evaluated using Controlling nutritional status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), Advanced Lung Cancer Inflammation Index (ALI), Prognostic Nutritional Index (PNI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Albumin-to-Globulin Ratio (AGR) nutritional-related indicators. Multivariate weighted logistic and Cox regression models were employed to assess the correlation between the six nutritional-related indicators and the risk of COPD and as all-cause mortality. The restricted cubic spline tests were applied to explore potential nonlinear relationships, and ROC curves and C-index analyses were conducted to compare the predictive capabilities of different indicators. Stratified analysis and propensity score matching (PSM) to assess the robustness of the results.ResultsIn this study, Lower ALI, lower GNRI, and higher CONUT scores were positively correlated with an increased risk of COPD (OR: 1.77, 95% CI: 1.10–2.84) (OR: 8.66, 95% CI: 2.95–25.5), and (OR: 5.11, 95% CI: 1.72–15.2), respectively. It was found that ALI and GNRI had a non-linear relationship with the risk of COPD. After propensity score matching (PSM), the associations between ALI, GNRI, CONUT scores, and COPD remained consistent. Lower ALI, PNI, and GNRI scores were positively associated with all-cause mortality in COPD patients (HR: 2.41, 95% CI: 1.10–5.27), (HR: 3.76, 95% CI: 1.89–7.48), and (HR: 4.55, 95% CI: 1.30–15.9), respectively, with GNRI displaying a non-linear relationship with all-cause mortality. ROC curve and C-index analyses indicated that ALI had the best predictive ability for both COPD risk and all-cause mortality.ConclusionALI, GNRI, and CONUT scores are correlated with the risk of COPD, while ALI, PNI, and GNRI scores are associated with all-cause mortality in COPD patients. Compared to other nutritional scores, ALI may provide more effective predictive value for both risk and all-cause mortality.
Prognostic significance of histologic phenotype in periampullary adenocarcinomas
Authors: Kim Hee-Sung , Heo Chang-Min , Choi Yoo-Shin , Suh Suk-Won , Lee Seung Eun 
Published: July 2024

BackgroundPeriampullary adenocarcinomas typically exhibit either intestinal or pancreatobiliary (PB) differentiation, and the type of differentiation may be prognostically more important than the anatomic site of origin. This study aimed to evaluate prognostic significance of histological type of periampullary carcinomas.MethodsMicroscopic slides from 110 consecutive pancreatoduodenectomies performed between 2010 and 2020 were reviewed and classified as intestinal or PB type. Clinicopathological factors were compared between PB-(n=93) and intestinal-type (n=17) differentiation.ResultsThe intestinal type included significantly more patients with well-differentiated histology (35.3% vs. 11.8%, p=0.001) and fewer patients with perineural invasion (41.2% vs. 76.4%, p=0.029), advanced T stage (&gt; T3; 41.2% vs.74.2%, p=0.007), and systemic recurrence (71.4% vs. 92.9%, p=0.005) than PB type. The 5-year-overall survival rate of intestinal-type was significantly higher than that of PB-type (58.8% vs. 20.4%, p=0.003). When pancreatic cancer was separately analyzed, the intestinal type showed the best 5-year-overall survival rate, with no significant difference between the PB types excluding PDAC and PDAC (39.4% vs. 19.2%, p=0.148). In multivariate analysis, curative resection (hazard ratio, 0.417; 95% CI, 0.219-0.792, p=0.008) was the only significant prognostic factor.ConclusionAlthough intestinal histologic phenotype was not an independent prognostic factor on multivariate analysis, it showed pathologic features associated with better survival, while the PB type showed more aggressive tumor biology and consequently worse survival. Further studies are needed to demonstrate the prognostic significance of histologic phenotype.