bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic Analysis of Protective Effects of Dl-3-n-Butylphthalide against mpp + -Induced Toxicity via downregulating P53 pathway in N2A Cells
Authors: Zhao Yuan , Zhang Jian , Zhang Yidan , Li Shuyue , Gao Ya , Chang Cui , Liu Xiang , Xu Lei , Yang Guofeng 
Published: January 2023

Abstract
Background
Dl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD.

Method
In our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC–MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein–protein interactions (PPI) by Cytoscape, DEPs were verified by western blot.

Result
A total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p < 0.05). Among the 417 DEPs, 140 were upregulated and 277 were downregulated in mpp + -induced N2A cells with NBP pretreatment. KEGG pathway analysis indicated that lysosome, phagosome, apoptosis, endocytosis and ferroptosis are the mainly enriched pathways. By using MCL clustering in PPI analysis, 48 clusters were generated and the subsequent KEGG analysis of the top 3 clusters revealed that P53 signaling pathway was recognized as the dominant pathway for NBP treatment.

Conclusion
NBP significantly relived mpp + -induced cell toxicity. The neuroprotective role of NBP was implicated with P53 signaling pathway in some extent. These findings will reinforce the understanding of the mechanism of NBP in PD and identify novel therapeutic targets.
The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis by regulating ROS and autophagy
Authors: Yu Qiao , Shi Huiying , Ding Zhen , Wang Zhe , Yao Hailing , Lin Rong 
Published: January 2023

Abstract
Background
The NLRP3 inflammasome activation is the molecular basis of Helicobacter pylori (Hp)-associated gastritis. Tripartite motif (TRIM) 31 is involved in diverse pathological events. However, whether TRIM31 plays a role in the activation of NLRP3 inflammasome in Hp infection is not clarified.

Methods
A mouse model of chronic Hp infection was established, and the gastric tissues were subjected to the polymerase chain reaction, western blotting, histopathological analysis, and RNA sequencing. The mitochondrial membrane potential and ROS in the human gastric epithelium GES-1 cells with or without Hp infection were measured by flow cytometry. GES-1 cells with or without TRIM31 knockdown were transfected with mCherry-EGFP-LC3 adenovirus. After rapamycin and bafilomycin A1 stimulation, autophagy flux in the above primed GES-1 cells was assessed by laser confocal microscope. Lysosomal acidification and expression levels of cathepsin B and cathepsin D in GES-1 cells with Hp infection were measured.

Results
NLRP3 inflammasome was activated in the gastric tissues of mice with chronic Hp infection in vivo and the GES-1 cells with Hp infection in vitro. TRIM31 was downregulated in Hp infection. TRIM31 negatively regulated the NLRP3 inflammasome activation. Enhanced ROS, impaired autophagy flux, and decreased expression of lysosomal cathepsin B and cathepsin D were observed in TRIM31-deficient GES-1 cells with Hp infection. In turn, inhibition of ROS led to the decreased expression of NLRP3 inflammasome.

Conclusions
Together, our data identified that TRIM31 negatively regulated the activation of NLRP3 inflammasome in Hp-associated gastritis by affecting ROS and autophagy of gastric epithelial cells.
(Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota
Authors: Wang Juan , Ding Yuwei , Li Dan , Zhu Ning , Nishiyama Akira , Yuan Ying 
Published: January 2023

Abstract
Background
We previously found that (pro)renin receptor ((P)RR) augments Wnt3 protein without affecting Wnt3 gene transcription in colorectal cancer (CRC) cells, thus contributes to CRC initiation. The present study aims to investigate whether (P)RR further promotes CRC progression following oncogenesis and the related mechanisms. Notably, we deeply elaborate how (P)RR affects Wnt3 protein level and the key enzyme that mediates this process.

Methods
Immunohistochemistry, western blotting and immunofluorescence were performed to detect protein expression status. A kind of gastrointestinal epithelium-specific ATP6AP2 ((P)RR encoding gene) knock-in mice were generated using Crispr/Cas9 system.

Results
We found that increased (P)RR expression in primary CRC lesions is positively associated with higher Wnt3 protein level and disease progression. Progressive CRC presents less colocalization of Wnt3 and an E3 ubiquitin ligase NEDD4L in primary lesions than non-progressive CRC. In colon cancer cells, (P)RR dramatically inhibits the NEDD4L-mediated Wnt3 protein ubiquitination. ATP6AP2 knock-in mice show more diminished Wnt3-NEDD4L colocalization in their gut epithelium in comparison to wildtype mice. They also have abnormal gut bacterial flora distribution. Especially, Lachnospiraceae_NK4A136 and Bacteroides genus, which are generally protective against CRC, are suppressed in guts of ATP6AP2 knock-in mice.

Conclusions
Collectively, (P)RR promotes CRC progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota.
Active school commuting in adolescents from 28 countries across Africa, the Americas, and Asia: a temporal trends study
Authors: Felez-Nobrega Mireia , Werneck André O. , Bauman Adrian , Haro Josep Maria , Koyanagi Ai 
Published: January 2023

Abstract
Background
Evidence examining trends in active school commuting among adolescents are mainly single-country studies, and principally focused on high-income countries. Thus, the present study aims to examine temporal trends in adolescents’ active school commuting and to examine if there are differences in such trends by sex. We used nationally representative samples of 28 countries, which were predominantly low- and middle-income countries (LMICs), covering 5 different WHO regions.

Methods
Data from the Global School-based Student Health Survey 2004–2017 were analyzed in 177,616 adolescents [mean (SD) age: 13.7 (1.0) years; 50.7% girls]. Active school commuting was self-reported (frequency of walking or riding a bike to and from school in the past 7 days). The prevalence and 95%CI of active school commuting (i.e., ≥ 3 days/week) was calculated for the overall sample and by sex for each survey. Crude linear trends in active school commuting were assessed by linear regression models. Interaction analyses were conducted to examine differing trends among boys and girls.

Results
Trends in active school commuting were heterogeneous across countries, with results showing stable patterns for the majority (16/28), decreasing trends for some (7/28) and increasing trends over time for a few (5/28). The majority of countries showed no differences in active school commuting trends between girls and boys.

Conclusions
The quantification of changes in adolescents’ active school commuting over time, together with a deeper understanding of local determinants for such behaviors will provide valuable evidence to inform the development of tailored and context-specific actions.
Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function
Authors: Konstantinidis Evangelos , Portal Benjamin , Mothes Tobias , Beretta Chiara , Lindskog Maria , Erlandsson Anna 
Published: January 2023

Abstract
Background
Astrocytes are crucial for maintaining brain homeostasis and synaptic function, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Our previous data demonstrate that astrocytes ingest large amounts of aggregated amyloid-beta (Aβ), but then store, rather than degrade the ingested material, which leads to severe cellular stress. However, the involvement of pathological astrocytes in AD-related synaptic dysfunction remains to be elucidated.

Methods
In this study, we aimed to investigate how intracellular deposits of Aβ in astrocytes affect their interplay with neurons, focusing on neuronal function and viability. For this purpose, human induced pluripotent stem cell (hiPSC)-derived astrocytes were exposed to sonicated Αβ42 fibrils. The direct and indirect effects of the Αβ-exposed astrocytes on hiPSC-derived neurons were analyzed by performing astrocyte–neuron co-cultures as well as additions of conditioned media or extracellular vesicles to pure neuronal cultures.

Results
Electrophysiological recordings revealed significantly decreased frequency of excitatory post-synaptic currents in neurons co-cultured with Aβ-exposed astrocytes, while conditioned media from Aβ-exposed astrocytes had the opposite effect and resulted in hyperactivation of the synapses. Clearly, factors secreted from control, but not from Aβ-exposed astrocytes, benefited the wellbeing of neuronal cultures. Moreover, reactive astrocytes with Aβ deposits led to an elevated clearance of dead cells in the co-cultures.

Conclusions
Taken together, our results demonstrate that inclusions of aggregated Aβ affect the reactive state of the astrocytes, as well as their ability to support neuronal function.
Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study
Authors: De Castro Nathalie , Brun Alexandre , Sellier Pierre , Hamet Gwenn , Mechaï Frédéric , Garrait Valérie , Chabrol Amélie , Bouldouyre Marie-Anne , Froguel Eric , Troisvallets Didier , Caraux-Paz Pauline , Delaugerre Constance , Rozenbaum Willy , Molina Jean-Michel 
Published: January 2023

Abstract
Objectives
We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection.

Methods
We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF).

Results
382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38–51), who had been on ART for a median of 7 years (IQR 4–13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4–86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64–8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions.

Conclusion
In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.
Rapid remodeling observed at mid-term in-vivo study of a smart reinforced acellular vascular graft implanted on a rat model
Authors: Obiweluozor Francis O. , Kayumov Mukhammad , Kwak Yujin , Cho Hwa-Jin , Park Chan-Hee , Park Jun-kyu , Jeong Yun-Jin , Lee Dong-Weon , Kim Do-Wan , Jeong In-Seok 
Published: January 2023

Abstract
Background
The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia.

Result
Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan).

Conclusions
The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.
CT-based machine learning radiomics predicts CCR5 expression level and survival in ovarian cancer
Authors: Wan Sheng , Zhou Tianfan , Che Ronghua , Li Ying , Peng Jing , Wu Yuelin , Gu Shengyi , Cheng Jiejun , Hua Xiaolin 
Published: January 2023

AbstractObjectiveWe aimed to evaluate the prognostic value of C-C motif chemokine receptor type 5 (CCR5) expression level for patients with ovarian cancer and to establish a radiomics model that can predict CCR5 expression level using The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) database.MethodsA total of 343 cases of ovarian cancer from the TCGA were used for the gene-based prognostic analysis. Fifty seven cases had preoperative computed tomography (CT) images stored in TCIA with genomic data in TCGA were used for radiomics feature extraction and model construction. 89 cases with both TCGA and TCIA clinical data were used for radiomics model evaluation. After feature extraction, a radiomics signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis. A prognostic scoring system incorporating radiomics signature based on CCR5 expression level and clinicopathologic risk factors was proposed for survival prediction.ResultsCCR5 was identified as a differentially expressed prognosis-related gene in tumor and normal sample, which were involved in the regulation of immune response and tumor invasion and metastasis. Four optimal radiomics features were selected to predict overall survival. The performance of the radiomics model for predicting the CCR5 expression level with 10-fold cross- validation achieved Area Under Curve (AUCs) of 0.770 and of 0.726, respectively, in the training and validation sets. A predictive nomogram was generated based on the total risk score of each patient, the AUCs of the time-dependent receiver operating characteristic (ROC) curve of the model was 0.8, 0.673 and 0.792 for 1-year, 3-year and 5-year, respectively. Along with clinical features, important imaging biomarkers could improve the overall survival accuracy of the prediction model.ConclusionThe expression levels of CCR5 can affect the prognosis of patients with ovarian cancer. CT-based radiomics could serve as a new tool for prognosis prediction.
The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis
Authors: Fazzini Brigitta , Märkl Tobias , Costas Christos , Blobner Manfred , Schaller Stefan J. , Prowle John , Puthucheary Zudin , Wackerhage Henning 
Published: January 2023

Abstract
Background
Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients.

Methods
We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle–Ottawa Scale.

Results
Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day −1.75% (95% CI −2.05, −1.45) of their rectus femoris thickness or −2.10% (95% CI −3.17, −1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%).

Conclusion
On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.
Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial
Authors: Zhang Yan , Ruan Guangfeng , Zheng Peng , Huang Sili , Zhou Xiaoni , Liu Xuelian , Hu Wenjie , Feng Huiting , Lin Yangyang , He Juanjuan , Wei Zhenhai , Zhang Jiangshan , Chang Qing , Wei Xiaomei , Fan Tao , Jiang Li , Ding Changhai 
Published: January 2023

Abstract
Background
Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and individualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype.

Methods
GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test).

Discussion
GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future.

Trial registration
ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.
Necrobiosis lipoidica of the breast associated with Crohn’s disease: a case report
Authors: Kelati Awatef , Durupt François , Balme Brigitte 
Published: January 2023

Abstract
Background
Necrobiosis lipoidica located to the breast; without evidence of glucose intolerance, is extremely rare, and its association to Crohn’s disease is not usual.

Case presentation
We report an interesting case of an association of necrobiosis lipoidica of the breast and Crohn’s disease in a 54-year-old Moroccan woman. Skin necrobiotic changes are a characteristic feature in necrobiosis lipoidica, but they are exceptional in metastatic Crohn’s disease, since there are only three published cases of necrobiotic skin lesions on the lower leg resembling erythema nodosum in metastatic Crohn’s disease.

Conclusions
On the basis of this rare observation, necrobiosis lipoidica without evidence of glucose intolerance should be recognized as a possible cutaneous manifestation or association of Crohn’s disease.