bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein
Authors: Zhang Hui-hui , Zhang An-qi , Peng Peng , Huang Liang , Liu Cai-ying , Nie Xin-rui , Hou De-fu , Zhang Xia , Li Shang-ze 
Published: January 2024

Abstract
Background
Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored.

Methods
The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer.

Results
USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination.

Conclusions
Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.
Improving economic access to healthy diets in first nations communities in high-income, colonised countries: a systematic scoping review
Authors: Lee Amanda J. , Herron Lisa-Maree , Rainow Stephan , Wells Lisa , Kenny Ingrid , Kenny Leon , Wells Imogen , Kavanagh Margaret , Bryce Suzanne , Balmer Liza 
Published: January 2024

Abstract
Background
Affordability of healthy food is a key determinant of the diet-related health of First Nations Peoples. This systematic scoping review was commissioned by the Ngaanyatjarra Pitjantjatjara Yankunytjatjara Women’s Council (NPYWC) in Central Australia to identify interventions to improve economic access to healthy food in First Nations communities in selected high-income, colonised countries.

Methods
Eight databases and 22 websites were searched to identify studies of interventions and policies to improve economic access to healthy food in First Nations communities in Australia, Canada, the United States or New Zealand from 1996 to May 2022. Data from full text of articles meeting inclusion criteria were extracted to a spreadsheet. Results were collated by descriptive synthesis. Findings were examined with members of the NPYWC Anangu research team at a co-design workshop.

Results
Thirty-five publications met criteria for inclusion, mostly set in Australia (37%) or the US (31%). Interventions (n = 21) were broadly categorised as price discounts on healthy food sold in communities (n = 7); direct subsidies to retail stores, suppliers and producers (n = 2); free healthy food and/or food vouchers provided to community members (n = 7); increased financial support to community members (n = 1); and other government strategies (n = 4).
Promising initiatives were: providing a box of food and vouchers for fresh produce; prescriptions for fresh produce; provision/promotion of subsidised healthy meals and snacks in community stores; direct funds transfer for food for children; offering discounted healthy foods from a mobile van; and programs increasing access to traditional foods. Providing subsidies directly to retail stores, suppliers and producers was least effective.
Identified enablers of effective programs included community co-design and empowerment; optimal promotion of the program; and targeting a wide range of healthy foods, particularly traditional foods where possible. Common barriers in the least successful programs included inadequate study duration; inadequate subsidies; lack of supporting resources and infrastructure for cooking, food preparation and storage; and imposition of the program on communities.

Conclusions
The review identified 21 initiatives aimed at increasing affordability of healthy foods in First Nations communities, of which six were deemed promising. Five reflected the voices and experiences of members of the NPYWC Anangu research team and will be considered by communities for trial in Central Australia. Findings also highlight potential approaches to improve economic access to healthy foods in First Nations communities in other high-income colonised countries.

Trial registration
PROSPERO CRD42022328326.
Intracellular delivery of Parkin-RING0-based fragments corrects Parkin-induced mitochondrial dysfunction through interaction with SLP-2
Authors: Zanon Alessandra , Guida Marianna , Lavdas Alexandros A. , Corti Corrado , Castelo Rueda Maria Paulina , Negro Alessandro , Pramstaller Peter P. , Domingues Francisco S. , Hicks Andrew A. , Pichler Irene 
Published: January 2024

Abstract
Background
Loss-of-function mutations in the PRKN gene, encoding Parkin, are the most common cause of autosomal recessive Parkinson’s disease (PD). We have previously identified mitoch
ondrial Stomatin-like protein 2 (SLP-2), which functions in the assembly of respiratory chain proteins, as a Parkin-binding protein. Selective knockdown of either Parkin or SLP-2 led to reduced mitochondrial and neuronal function in neuronal cells and Drosophila, where a double knockdown led to a further worsening of Parkin-deficiency phenotypes. Here, we investigated the minimal Parkin region involved in the Parkin-SLP-2 interaction and explored the ability of Parkin-fragments and peptides from this minimal region to restore mitochondrial function.

Methods
In fibroblasts, human induced pluripotent stem cell (hiPSC)-derived neurons, and neuroblastoma cells the interaction between Parkin and SLP-2 was investigated, and the Parkin domain responsible for the binding to SLP-2 was mapped. High resolution respirometry, immunofluorescence analysis and live imaging were used to analyze mitochondrial function.

Results
Using a proximity ligation assay, we quantitatively assessed the Parkin-SLP-2 interaction in skin fibroblasts and hiPSC-derived neurons. When PD-associated PRKN mutations were present, we detected a significantly reduced interaction between the two proteins. We found a preferential binding of SLP-2 to the N-terminal part of Parkin, with a highest affinity for the RING0 domain. Computational modeling based on the crystal structure of Parkin protein predicted several potential binding sites for SLP-2 within the Parkin RING0 domain. Amongst these, three binding sites were observed to overlap with natural PD-causing missense mutations, which we demonstrated interfere substantially with the binding of Parkin to SLP-2. Finally, delivery of the isolated Parkin RING0 domain and a Parkin mini-peptide, conjugated to cell-permeant and mitochondrial transporters, rescued compromised mitochondrial function in Parkin-deficient neuroblastoma cells and hiPSC-derived neurons with endogenous, disease causing PRKN mutations.

Conclusions
These findings place further emphasis on the importance of the protein–protein interaction between Parkin and SLP-2 for the maintenance of optimal mitochondrial function. The possibility of restoring an abolished binding to SLP-2 by delivering the Parkin RING0 domain or the Parkin mini-peptide involved in this specific protein–protein interaction into cells might represent a novel organelle-specific therapeutic approach for correcting mitochondrial dysfunction in Parkin-linked PD.
A benchmarking framework for the accurate and cost-effective detection of clinically-relevant structural variants for cancer target identification and diagnosis
Authors: Zhuang Guiwu , Zhang Xiaotao , Du Wenjing , Xu Libin , Ma Jiyong , Luo Haitao , Tang Hongzhen , Wang Wei , Wang Peng , Li Miao , Yang Xu , Wu Dongfang , Fang Shencun 
Published: January 2024

Abstract
Background
Accurate clinical structural variant (SV) calling is essential for cancer target identification and diagnosis but has been historically challenging due to the lack of ground truth for clinical specimens. Meanwhile, reduced clinical-testing cost is the key to the widespread clinical utility.

Methods
We analyzed massive data from tumor samples of 476 patients and developed a computational framework for accurate and cost-effective detection of clinically-relevant SVs. In addition, standard materials and classical experiments including immunohistochemistry and/or fluorescence in situ hybridization were used to validate the developed computational framework.

Results
We systematically evaluated the common algorithms for SV detection and established an expert-reviewed SV call set of 1,303 tumor-specific SVs with high-evidence levels. Moreover, we developed a random-forest-based decision model to improve the true positive of SVs. To independently validate the tailored ‘two-step’ strategy, we utilized standard materials and classical experiments. The accuracy of the model was over 90% (92–99.78%) for all types of data.

Conclusion
Our study provides a valuable resource and an actionable guide to improve cancer-specific SV detection accuracy and clinical applicability.
Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox
Authors: Wang Wenxuan , Yang Tingting , Chen Sihui , Liang Liying , Wang Yingxin , Ding Yin , Xiong Wei , Ye Xiuhong , Guo Yonglong , Shen Shuhao , Chen Hang , Chen Jiansu 
Published: January 2024

Abstract
Background
Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics.

Results
Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation.

Conclusions
Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.
LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer
Authors: Ma Xinyi , Chen Zhenhua , Chen Wei , Chen Ziyuan , Shang Yue , Zhao Yikai , Li Leyi , Zhou Chengwei , He Jinxian , Meng Xiaodan 
Published: January 2024

Abstract
Background
Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery.

Methods
The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency.

Results
The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells’ proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease.

Conclusions
This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.
Bisphenol A triggers apoptosis in mouse pre-antral follicle granulosa cells via oxidative stress
Authors: Wang Chen , He Chaofan , Xu Shumin , Gao Yuanyuan , Wang Kaixian , Liang Meng , Hu Ke 
Published: January 2024

Abstract
Background
Bisphenol A (BPA), an endocrine disrupting chemical with weak estrogenic and anti-androgenic activity, is widely present in various environmental media and organisms. It has certain reproductive toxicity and can cause a variety of female reproductive system diseases. Although BPA-stimulated apoptosis of granulosa cells has been widely elaborated, the effect of BPA on mouse pre-antral follicle granulosa cells (mpGCs) has not been well elucidated.

Results
In this study, the results of live-dead cell staining showed that high concentrations of BPA severely impaired mpGCs growth viability and affected the cell cycle transition of mpGCs. We confirmed that BPA promotes the production of reactive oxygen species (ROS) and facilitates oxidative stress in mpGCs. In addition, immunofluorescence, transmission electron microscopy, and flow cytometry experiments demonstrated that BPA treatment for mpGCs resulted in apoptotic features, such as rounding, cytoplasmic crinkling, and mitochondrial damage. This was accompanied by a large production of ROS and apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. RNA-seq data showed that several apoptosis-related pathways were enriched in the high concentration BPA-treated group compared with the normal group, such as the p53 pathway, MAPK pathway, etc.

Conclusions
These results suggest that cells undergo oxidative stress effects and apoptosis after BPA treatment for mpGCs, which affects normal follicle development. The potential mechanism of BPA-induced female reproductive toxicity was elucidated, while providing a research basis for the prevention and treatment of female reproductive diseases.
Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies
Authors: Tu Hsin-Fang , Wong Margaret , Tseng Ssu-Hsueh , Ingavat Nattha , Olczak Pola , Notarte Kin Israel , Hung Chien-fu , Roden Richard B.S. 
Published: January 2024

Abstract
Background
MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance.

Results
A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope.

Conclusion
Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.
Evidence of steady-state fibroblast subtypes in the normal human breast as cells-of-origin for perturbed-state fibroblasts in breast cancer
Authors: Bagger Mikkel Morsing , Sjölund Jonas , Kim Jiyoung , Kohler Katharina Theresa , Villadsen René , Jafari Abbas , Kassem Moustapha , Pietras Kristian , Rønnov-Jessen Lone , Petersen Ole William 
Published: January 2024

Abstract
Background
Human breast cancer most frequently originates within a well-defined anatomical structure referred to as the terminal duct lobular unit (TDLU). This structure is endowed with its very own lobular fibroblasts representing one out of two steady-state fibroblast subtypes—the other being interlobular fibroblasts. While cancer-associated fibroblasts (CAFs) are increasingly appreciated as covering a spectrum of perturbed states, we lack a coherent understanding of their relationship—if any—with the steady-state fibroblast subtypes. To address this, we here established two autologous CAF lines representing inflammatory CAFs (iCAFs) and myofibroblast CAFs (myCAFs) and compared them with already established interlobular- and lobular fibroblasts with respect to their origin and impact on tumor formation.

Methods
Primary breast tumor-derived CAFs were transduced to express human telomerase reverse transcriptase (hTERT) and sorted into CD105low and CD105high populations using fluorescence-activated cell sorting (FACS). The two populations were tested for differentiation similarities to iCAF and myCAF states through transcriptome-wide RNA-Sequencing (RNA-Seq) including comparison to an available iCAF-myCAF cell state atlas. Inference of origin in interlobular and lobular fibroblasts relied on RNA-Seq profiles, immunocytochemistry and growth characteristics. Osteogenic differentiation and bone formation assays in culture and in vivo were employed to gauge for origin in bone marrow-derived mesenchymal stem cells (bMSCs). Functional characteristics were assessed with respect to contractility in culture and interaction with tumor cells in mouse xenografts. The cells’ gene expression signatures were tested for association with clinical outcome of breast cancer patients using survival data from The Cancer Genome Atlas database.

Results
We demonstrate that iCAFs have properties in common with interlobular fibroblasts while myCAFs and lobular fibroblasts are related. None of the CAFs qualify as bMSCs as revealed by lack of critical performance in bone formation assays. Functionally, myCAFs and lobular fibroblasts are almost equally tumor promoting as opposed to iCAFs and interlobular fibroblasts. A myCAF gene signature is found to associate with poor breast cancer-specific survival.

Conclusions
We propose that iCAFs and myCAFs originate in interlobular and lobular fibroblasts, respectively, and more importantly, that the tumor-promoting properties of lobular fibroblasts render the TDLU an epicenter for breast cancer evolution.
Molecular imaging for evaluation of synovitis associated with osteoarthritis: a narrative review
Authors: Lee Kwanghoon , Niku Soheil , Koo Sonya J. , Belezzuoli Ernest , Guma Monica 
Published: January 2024

AbstractRecent evidence highlights the role of low-grade synovial inflammation in the progression of osteoarthritis (OA). Inflamed synovium of OA joints detected by imaging modalities are associated with subsequent progression of OA. In this sense, detecting and quantifying synovitis of OA by imaging modalities may be valuable in predicting OA progressors as well as in improving our understanding of OA progression. Of the several imaging modalities, molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has an advantage of visualizing the cellular or subcellular events of the tissues. Depending on the radiotracers used, molecular imaging method can potentially detect and visualize various aspects of synovial inflammation. This narrative review summarizes the recent progresses of imaging modalities in assessing inflammation and OA synovitis and focuses on novel radiotracers. Recent studies about imaging modalities including ultrasonography (US), magnetic resonance imaging (MRI), and molecular imaging that were used to detect and quantify inflammation and OA synovitis are summarized. Novel radiotracers specifically targeting the components of inflammation have been developed. These tracers may show promise in detecting inflamed synovium of OA and help in expanding our understanding of OA progression.