bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRABP1-complexes in exosome secretion
Authors: Nhieu Jennifer , Wei Chin-Wen , Ludwig Megan , Drake Justin M. , Wei Li-Na 
Published: July 2024

Abstract
Background
Cellular retinoic acid binding protein 1 (CRABP1) mediates rapid, non-canonical activity of retinoic acid (RA) by forming signalosomes via protein-protein interactions. Two signalosomes have been identified previously: CRABP1-MAPK and CRABP1-CaMKII. Crabp1 knockout (CKO) mice exhibited altered exosome profiles, but the mechanism of CRABP1 action was unclear. This study aimed to screen for and identify novel CRABP1 signalosomes that could modulate exosome secretion by using a combinatorial approach involving biochemical, bioinformatic and molecular studies.

Methods
Immunoprecipitation coupled with mass spectrometry (IP-MS) identified candidate CRABP1-interacting proteins which were subsequently analyzed using GO Term Enrichment, Functional Annotation Clustering; and Pathway Analysis. Gene expression analysis of CKO samples revealed altered expression of genes related to exosome biogenesis and secretion. The effect of CRABP1 on exosome secretion was then experimentally validated using CKO mice and a Crabp1 knockdown P19 cell line.

Results
IP-MS identified CRABP1-interacting targets. Bioinformatic analyses revealed significant association with actin cytoskeletal dynamics, kinases, and exosome secretion. The effect of CRABP1 on exosome secretion was experimentally validated by comparing circulating exosome numbers of CKO and wild type (WT) mice, and secreted exosomes from WT and siCRABP1-P19 cells. Pathway analysis identified kinase signaling and Arp2/3 complex as the major pathways where CRABP1-signalosomes modulate exosome secretion, which was validated in the P19 system.

Conclusion
The combinatorial approach allowed efficient screening for and identification of novel CRABP1-signalosomes. The results uncovered a novel function of CRABP1 in modulating exosome secretion, and suggested that CRABP1 could play roles in modulating intercellular communication and signal propagation.
Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis
Authors: Azeze Getnet Gedefaw , Wu Ling , Alemu Bekalu Kassie , Lee Wing Fong , Fung Linda Wen Ying , Cheung Eva Chun Wai , Zhang Tao , Wang Chi Chiu 
Published: July 2024

Abstract
Background
Endometriosis is one of the most common gynaecological diseases, yet it lacks efficient biomarkers for early detection and unravels disease mechanisms. Proteomic profiling has revealed diverse patterns of protein changes in various clinical samples. Integrating and systematically analysing proteomics data can facilitate the development of biomarkers, expediting diagnosis and providing insights for potential clinical and therapeutic applications. Hence, this systematic review and meta-analysis aimed to explore potential non-invasive diagnostic biomarkers in various biological samples and therapeutic targets for endometriosis.

Methods
Online databases, including Scopus, PubMed, Web of Science, MEDLINE, Embase via Ovid, and Google Scholar, were searched using MeSH terms. Two independent authors screened the articles, extracted the data, and assessed the methodological quality of the included studies. GO and KEGG analyses were performed to identify the pathways that were significantly enriched. Protein‑protein interaction and hub gene selection analyses were also conducted to identify biomarker networks for endometriosis.

Results
Twenty-six observational studies with a total of 2,486 participants were included. A total of 644 differentially expressed proteins (180 upregulated and 464 downregulated) were identified from 9 studies. Proteins in peripheral blood exhibited a sensitivity and specificity of 38-100% and 59-99%, respectively, for detecting endometriosis, while proteins in urine had a sensitivity of 58-91% and specificity of 76-93%. Alpha-1-antitrypsin, albumin, and vitamin D binding proteins were significantly DEPs in both serum and urine. Complement C3 is commonly expressed in serum, menstrual blood, and cervical mucus. Additionally, S100-A8 is commonly expressed in both menstrual blood and cervical mucus. Haptoglobin is commonly detected in both serum and plasma, whereas cathepsin G is found in urine, serum, and plasma. GO and KEGG enrichment analyses revealed that proteoglycans in cancer pathways, which regulate cell-to-cell interactions, modulate the extracellular matrix, and promote the proliferation and invasion of endometrial cells, are commonly enriched in serum and urine.

Conclusion
This comprehensive study revealed potential proteomes that were significantly differentially expressed in women with endometriosis utilizing various non-invasive clinical samples. Exploring common differentially expressed proteins in various biological samples provides insights into the diagnosis and pathophysiology of endometriosis, as well as potential clinical and therapeutic applications.

Graphical abstract
Facilitating the use of the target product profile in academic research: a systematic review
Authors: Ibnidris Aliaa , Liaskos Nektarios , Eldem Ece , Gunn Angus , Streffer Johannes , Gold Michael , Rea Mike , Teipel Stefan , Gardiol Alejandra , Boccardi Marina 
Published: July 2024

Abstract
Background
The Target Product Profile (TPP) is a tool used in industry to guide development strategies by addressing user needs and fostering effective communication among stakeholders. However, they are not frequently used in academic research, where they may be equally useful. This systematic review aims to extract the features of accessible TPPs, to identify commonalities and facilitate their integration in academic research methodology.

Methods
We searched peer-reviewed papers published in English developing TPPs for different products and health conditions in four biomedical databases. Interrater agreement, computed on random abstract and paper sets (Cohen’s Kappa; percentage agreement with zero tolerance) was > 0.91. We interviewed experts from industry contexts to gain insight on the process of TPP development, and extracted general and specific features on TPP use and structure.

Results
138 papers were eligible for data extraction. Of them, 92% (n = 128) developed a new TPP, with 41.3% (n = 57) focusing on therapeutics. The addressed disease categories were diverse; the largest (47.1%, n = 65) was infectious diseases. Only one TPP was identified for several fields, including global priorities like dementia. Our analyses found that 56.5% of papers (n = 78) was authored by academics, and 57.8% of TPPs (n = 80) featured one threshold level of product performance. The number of TPP features varied widely across and within product types (n = 3–44). Common features included purpose/context of use, shelf life for drug stability and validation aspects. Most papers did not describe the methods used to develop the TPP. We identified aspects to be taken into account to build and report TPPs, as a starting point for more focused initiatives guiding use by academics.

Discussion
TPPs are used in academic research mostly for infectious diseases and have heterogeneous features. Our extraction of key features and common structures helps to understand the tool and widen its use in academia. This is of particular relevance for areas of notable unmet needs, like dementia. Collaboration between stakeholders is key for innovation. Tools to streamline communication such as TPPs would support the development of products and services in academia as well as industry.
HMGB1/TREM2 positive feedback loop drives the development of radioresistance and immune escape of glioblastoma by regulating TLR4/Akt signaling
Authors: Qiu Hui , Shao Zhiying , Wen Xin , Qu Debao , Liu Zhengyang , Chen Ziqin , Zhang Xinyan , Ding Xin , Zhang Longzhen 
Published: July 2024

Abstract
Background
Radioresistance and immune escape are crucial reasons for unsatisfactory therapeutic effects of glioblastoma (GBM). Although triggering receptor expressed on myeloid cells-2 (TREM2) involved in forming immunosuppressive microenvironment, but the underlying mechanism and its roles in mediating cancer radioresistance remain unclear, moreover, the efficient delivery of drugs targeting TREM2 to GBM encounters serious challenges. Hence, this study aimed to elucidate the effect and mechanisms of targeted TREM2 silencing on reversing the radioresistance and immune escape of GBM aided by a glutathione-responsive biomimetic nanoparticle (NP) platform.

Methods
Radioresistant GBM cell lines and TREM2 stable knockdown GBM cell lines were firstly established. RNA sequencing, colony formation assay, western blot, enzyme-linked immunosorbent assay and co-immunoprecipitation assay were used to detect the molecular mechanisms of TREM2 in regulating the radioresistance and immune escape of GBM. The glutathione-responsive biomimetic NP, angiopep-2 (A2)- cell membrane (CM)-NP/siTREM2/spam1, was then constructed to triply and targeted inhibit TREM2 for in vivo study. Orthotopic GBM-bearing mouse models were established to evaluate the anti-GBM effect of TREM2 inhibition, multiplex immunofluorescence assay was conducted to detect the infiltration of immune cells.

Results
TREM2 was a regulator in accelerating the radioresistance and immune escape of GBM through participating in DNA damage repair and forming a positive feedback loop with high mobility group box 1 (HMGB1) to cascade the activation of Toll-like receptor 4 (TLR4)/protein kinase B (Akt) signaling. A2-CM-NP/siTREM2/spam1 was successfully synthesized with excellent passive targeting, active targeting and homologous targeting, and the in vivo results exhibited its remarkable anti-GBM therapeutic effect through promoting the infiltration of type 1 helper T cells and CD8+T cells, reducing the infiltration of type 2 helper T cells and regulatory T cells, repolarizing macrophages to M1-type, and decreasing the secretion of pro-tumor and immunosuppressive cytokines.

Conclusions
Targeting TREM2 therapy is a promising avenue for optimizing radiotherapy and immunotherapy to improve the prognosis of GBM patients.
The SPI1/SMAD5 cascade in the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells: a mechanism study
Authors: Zhang Junchao , Mao Yi , Rao Jianwei 
Published: July 2024

Abstract
Background
Dysregulation of osteogenic differentiation is a crucial event during osteoporosis. The bioactive phytochemical icariin has become an anti-osteoporosis candidate. Here, we elucidated the mechanisms underlying the promoting function of icariin in osteogenic differentiation.

Methods
Murine pre-osteoblast MC3T3-E1 cells were stimulated with dexamethasone (DEX) to induce osteogenic differentiation, which was evaluated by an Alizarin Red staining assay and ALP activity measurement. The mRNA amounts of SPI1 and SMAD5 were detected by real-time quantitative PCR. Expression analysis of proteins, including osteogenic markers (OPN, OCN and RUNX2) and autophagy-associated proteins (LC3, Beclin-1, and ATG5), was performed by immunoblotting. The binding of SPI1 and the SMAD5 promoter was predicted by the Jaspar2024 algorithm and confirmed by chromatin immunoprecipitation (ChIP) experiments. The regulation of SPI1 in SMAD5 was examined by luciferase assays.

Results
During osteogenic differentiation of MC3T3-E1 cells, SPI1 and SMAD5 were upregulated. Functionally, SPI1 overexpression enhanced autophagy and osteogenic differentiation of MC3T3-E1 cells, while SMAD5 downregulation exhibited opposite effects. Mechanistically, SPI1 could enhance SMAD5 transcription and expression. Downregulation of SMAD5 also reversed SPI1 overexpression-induced autophagy and osteogenic differentiation in MC3T3-E1 cells. In MC3T3-E1 cells under DEX stimulation, icariin increased SMAD5 expression by upregulating SPI1. Furthermore, icariin could attenuate SPI1 depletion-imposed inhibition of autophagy and osteogenic differentiation of MC3T3-E1 cells.

Conclusion
Our findings demonstrate that the SPI1/SMAD5 cascade, with the ability to enhance osteogenic differentiation, underlies the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells.
Designing an implementation science clinical trial to integrate hypertension and cardiovascular diseases care into existing HIV services package in Botswana (InterCARE)
Authors: Youssouf Nabila , Mogaetsho Gaone Edwin , Moshomo Thato , Gaolathe Tendani , Ponatshego Ponego , Ramotsababa Mareko , Molefe-Baikai Onkabetse Julia , Dintwa Evelyn , Kiki Tsaone , Van Pelt Amelia E. , Steger-May Karen , Bogart Laura M. , Jaffar Shabbar , Gala Pooja , Wang Duolao , Seipone Khumo , Bennett Kara , Hurwitz Kathleen Wirth , Kebotsamang Kago , Hirschhorn Lisa R. , Mosepele Mosepele 
Published: July 2024

Abstract
Background
Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies.

Methods
The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes.
InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial.

Discussion
If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region.

Trial registration
ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1.
Cardiovascular disease among bariatric surgery candidates: coronary artery screening and the impact of metabolic syndrome
Authors: Nie Yuntao , Zong Haoyu , Li Zhengqi , Wang Pengpeng , Zhang Nianrong , Zhou Biao , Wang Zhe , Zhang Lei , Wang Siqi , Huang Yishan , Tian Ziru , Chou Sai , Zhao Xingfei , Liu Baoyin , Meng Hua 
Published: July 2024

Abstract
Background
Obesity is known as a risk factor for cardiovascular disease (CVD). However, there is an absence of preoperative cardiac risk assessment in bariatric surgery candidates and the incidence of CVD among these high-risk patients is still unknown.

Methods
A consecutive series of bariatric surgery candidates at two Chinese tertiary hospitals received coronary CT angiography or coronary angiography from 2017 to 2023. Patients were categorized as metabolically unhealthy obesity (MUO) and metabolically healthy obesity (MHO) based on the presence or absence of MetS. CVD was diagnosed based on the maximum intraluminal stenosis > 1% in any of the segments of the major epicardial coronary arteries. Obstructive CVD was defined as coronary stenosis ≥ 50%. Binary multivariable logistic regression was performed to analyze the association between CVD and metabolic status. The number of principal MetS components was categorized into zero (without glycemic, lipid, and BP components), one (with one of the components), two (with any two components), and three (with all components) to explore their association with CVD.

Results
A total of 1446 patients were included in the study. The incidence of CVD and obstructive CVD were 31.7% and 9.6%. Compared with MHO patients, MUO patients had a significantly higher incidence of mild (13.7% vs. 6.1%, P < 0.05), moderate (7.4% vs. 0.8%, P < 0.05), and severe CVD (3.1% vs. 0%, P < 0.05). Following complete adjustment, compared with zero or one component, two principal MetS components was found to be associated with a notable increase in the risk of CVD (OR 2.05, 95% CI 1.18–3.58, P < 0.05); three principal MetS components were observed to have a higher risk of CVD and obstructive CVD (OR 2.68, 95% CI 1.56–4.62, P < 0.001; OR 3.93, 95% CI 1.19–12.93, P < 0.05). Each increase in the number of principal MetS components correlated with a 1.47-fold (95% CI 1.20–1.81, P < 0.001) and 1.78-fold (95% CI 1.24–2.55, P < 0.05) higher risk of CVD and obstructive CVD, respectively.

Conclusion
This study reported the incidence of CVD based on multicenter bariatric surgery cohorts. CVD is highly prevalent in patients with obesity, especially in MUO patients. Increased number of principal MetS components will significantly elevate the risk of CVD.
Transmission of Norwegian reindeer CWD to sheep by intracerebral inoculation results in an unusual phenotype and prion distribution
Authors: Harpaz Erez , Cazzaniga Federico Angelo , Tran Linh , Vuong Tram T. , Bufano Giuseppe , Salvesen Øyvind , Gravdal Maiken , Aldaz Devin , Sun Julianna , Kim Sehun , Celauro Luigi , Legname Giuseppe , Telling Glenn C. , Tranulis Michael A. , Benestad Sylvie L. , Espenes Arild , Moda Fabio , Ersdal Cecilie 
Published: July 2024

AbstractChronic wasting disease (CWD), a prion disease affecting cervids, has been known in North America (NA) since the 1960s and emerged in Norway in 2016. Surveillance and studies have revealed that there are different forms of CWD in Fennoscandia: contagious CWD in Norwegian reindeer and sporadic CWD in moose and red deer. Experimental studies have demonstrated that NA CWD prions can infect various species, but thus far, there have been no reports of natural transmission to non-cervid species. In vitro and laboratory animal studies of the Norwegian CWD strains suggest that these strains are different from the NA strains. In this work, we describe the intracerebral transmission of reindeer CWD to six scrapie-susceptible sheep. Detection methods included immunohistochemistry (IHC), western blot (WB), enzyme-linked immunosorbent assay (ELISA), real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA). In the brain, grey matter vacuolation was limited, while all sheep exhibited vacuolation of the white matter. IHC and WB conventional detection techniques failed to detect prions; however, positive seeding activity with the RT-QuIC and PMCA amplification techniques was observed in the central nervous system of all but one sheep. Prions were robustly amplified in the lymph nodes of all animals, mainly by RT-QuIC. Additionally, two lymph nodes were positive by WB, and one was positive by ELISA. These findings suggest that sheep can propagate reindeer CWD prions after intracerebral inoculation, resulting in an unusual disease phenotype and prion distribution with a low amount of detectable prions.
Baicalin and probenecid protect against Glaesserella parasuis challenge in a piglet model
Authors: Fu Shulin , Liu Siyu , Li Jingyang , Dong Qiaoli , Fu Yunjian , Luo Ronghui , Sun Yamin , Tian Xinyue , Liu Wei , Zong Bingbing , Ye Chun , Lu Qirong , Qiu Yinsheng , Guo Ling 
Published: July 2024

AbstractGlaesserella parasuis (G. parasuis) induces vascular damage and systemic inflammation. However, the mechanism by which it causes vascular damage is currently unclear. Baicalin has important anti-inflammatory, antibacterial and immunomodulatory functions. In this study, we explored the ability of baicalin and probenecid to protect against G. parasuis challenge in a piglet model. Sixty piglets were randomly divided into a control group; an infection group; a probenecid group; and 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups. The probenecid group and the 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups were injected intramuscularly with 20 mg/kg body weight (BW) probenecid and 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW baicalin, respectively. All piglets except those from the control group were injected intraperitoneally with 1 × 108 CFU of G. parasuis. The control group was injected intraperitoneally with TSB. The results showed baicalin and probenecid protected piglets against G. parasuis challenge, improved body weight and decreased temperature changes in piglets. Baicalin and probenecid attenuated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA levels in the blood for 48 h, inhibited the production of the nucleosides ATP, ADP, AMP and UMP from 24 to 72 h, reduced Panx-1/P2Y6/P2X7 expression, weakened NF-kB, AP-1, NLRP3/Caspase-1 and ROCK/MLCK/MLC signalling activation, and upregulated VE-cadherin expression in the blood vessels of piglets challenged with G. parasuis. Baicalin and probenecid alleviated pathological tissue damage in piglets induced by G. parasuis. Our results might provide a promising strategy to control and treat G. parasuis infection in the clinical setting.