bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amphiregulin induces CCN2 and fibronectin expression by TGF-β through EGFR-dependent pathway in lung epithelial cells
Authors: Cheng Wun-Hao , Kao Shih-Ya , Chen Chia-Ling , Yuliani Fara Silvia , Lin Lee-Yuan , Lin Chien-Huang , Chen Bing-Chang 
Published: December 2022

Abstract
Background
Airway fibrosis is one of the pathological characteristics of severe asthma. Transforming growth factor (TGF)-β has been known to promote epithelial-mesenchymal transition formation and to play a role in the progression of tissue fibrosis. Cellular communication network factor 2 (CCN2) and fibronectin (FN) are well-known markers of EMT and fibrosis. However, whether AREG is involved in TGF-β-induced CCN2 and FN expression in human lung epithelial cells is unknown.

Methods
AREG and FN were analyzed by immunofluorescence staining on ovalbumin-challenged mice. CCN2 and FN expression were evaluated in human lung epithelial (A459) cells following TGF or AREG treatment for the indicated times. Secreted AREG from A549 cells was detected by ELISA. Cell migration was observed by a wound healing assay. Chromatin immunoprecipitation was used to detect the c-Jun binding to the CCN2 promoter.

Results
AREG and FN expression colocalized in lung tissues from mice with ovalbumin-induced asthma by immunofluorescence staining. Moreover, TGF-β caused the release of AREG from A549 cells into the medium. Smad3 siRNA down-regulated AREG expression. AREG also stimulated CCN2 and FN expression, JNK and c-Jun phosphorylation, and cell migration in A549 cells. AREG small interfering (si) RNA inhibited TGF-β-induced expression of CCN2, FN, and cell migration. Furthermore, AREG-induced CCN2 and FN expression were inhibited by EGFR siRNA, a JNK inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). EGFR siRNA attenuated AREG-induced JNK and c-Jun phosphorylation. Moreover, SP600125 downregulated AREG-induced c-Jun phosphorylation.

Conclusion
These results suggested that AREG mediates the TGF-β-induced EMT in human lung epithelial cells through EGFR/JNK/AP-1 activation. Understanding the role of AREG in the EMT could foster the development of therapeutic strategies for airway remodeling in severe asthma.
Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids
Authors: Berk Kirsten A. , Borgeraas Heidi , Narverud Ingunn , Mulder Monique T. , Øyri Linn K. L. , Verhoeven Adrie J. M. , Småstuen Milada Cvancarova , Bogsrud Martin P. , Omland Torbjørn , Hertel Jens Kristoffer , Gjevestad Espen , Nordstrand Njord , Holven Kirsten B. , Hjelmesæth Jøran 
Published: December 2022

Abstract
Background
Limited evidence suggests that surgical and non-surgical obesity treatment differentially influence plasma Lipoprotein (a) [Lp(a)] levels. Further, a novel association between plasma arachidonic acid and Lp(a) has recently been shown, suggesting that fatty acids are a possible target to influence Lp(a). Here, the effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) were compared, and it was examined whether the effects were mediated by changes in plasma fatty acid (FA) levels.

Methods
The study includes two independent trials of patients with overweight or obesity. Trial 1: Two-armed intervention study including 82 patients who underwent a 7-week low energy diet (LED), followed by Roux-en-Y gastric bypass and 52-week follow-up (surgery-group), and 77 patients who underwent a 59-week energy restricted diet- and exercise-program (lifestyle-group). Trial 2: A clinical study including 134 patients who underwent a 20-week very-LED/LED (lifestyle-cohort).

Results
In the surgery-group, Lp(a) levels [median (interquartile range)] tended to increase in the pre-surgical LED-phase [17(7–68)-21(7–81)nmol/L, P = 0.05], but decreased by 48% after surgery [21(7–81)—11(7–56)nmol/L, P < 0.001]. In the lifestyle-group and lifestyle-cohort, Lp(a) increased by 36%[14(7–77)—19(7–94)nmol/L, P < 0.001] and 14%[50(14–160)—57(19–208)nmol/L, P < 0.001], respectively. Changes in Lp(a) were independent of weight loss. Plasma levels of total saturated FAs remained unchanged after surgery, but decreased after lifestyle interventions. Arachidonic acid and total n-3 FAs decreased after surgery, but increased after lifestyle interventions. Plasma FAs did not mediate the effects on Lp(a).

Conclusion
Bariatric surgery reduced, whereas lifestyle interventions increased plasma Lp(a), independent of weight loss. The interventions differentially influenced changes in plasma FAs, but these changes did not mediate changes in Lp(a).

Trial registration
Trial 1: Clinicaltrials.gov NCT00626964.
Trial 2: Netherlands Trial Register NL2140 (NTR2264).

Graphical abstract
Different coatings on magnetic nanoparticles dictate their degradation kinetics in vivo for 15 months after intravenous administration in mice
Authors: Portilla Yadileiny , Fernández-Afonso Yilian , Pérez-Yagüe Sonia , Mulens-Arias Vladimir , Morales M. Puerto , Gutiérrez Lucía , Barber Domingo F. 
Published: December 2022

Abstract
Background
The surface coating of iron oxide magnetic nanoparticle (MNPs) drives their intracellular trafficking and degradation in endolysosomes, as well as dictating other cellular outcomes. As such, we assessed whether MNP coatings might influence their biodistribution, their accumulation in certain organs and their turnover therein, processes that must be understood in vivo to optimize the design of nanoformulations for specific therapeutic/diagnostic needs.

Results
In this study, three different MNP coatings were analyzed, each conferring the identical 12 nm iron oxide cores with different physicochemical characteristics: 3-aminopropyl-triethoxysilane (APS), dextran (DEX), and dimercaptosuccinic acid (DMSA). When the biodistribution of these MNPs was analyzed in C57BL/6 mice, they all mainly accumulated in the spleen and liver one week after administration. The coating influenced the proportion of the MNPs in each organ, with more APS-MNPs accumulating in the spleen and more DMSA-MNPs accumulating in the liver, remaining there until they were fully degraded. The changes in the physicochemical properties of the MNPs (core size and magnetic properties) was also assessed during their intracellular degradation when internalized by two murine macrophage cell lines. The decrease in the size of the MNPs iron core was influenced by their coating and the organ in which they accumulated. Finally, MNP degradation was analyzed in the liver and spleen of C57BL/6 mice from 7 days to 15 months after the last intravenous MNP administration.

Conclusions
The MNPs degraded at different rates depending on the organ and their coating, the former representing the feature that was fundamental in determining the time they persisted. In the liver, the rate of degradation was similar for all three coatings, and it was faster than in the spleen. This information regarding the influence of coatings on the in vivo degradation of MNPs will help to choose the best coating for each biomedical application depending on the specific clinical requirements.

Graphical Abstract
Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases
Authors: Chen Chen , Zhou YuWei , Ning XinPeng , Li ShengLong , Xue DongDong , Wei CaiLv , Zhu Zhu , Sheng LongXiang , Lu BingZheng , Li Yuan , Ye XiaoYuan , Fu YunZhao , Bai Chuan , Cai Wei , Ding YuXuan , Lin SuiZhen , Yan GuangMei , Huang YiJun , Yin Wei 
Published: December 2022

Abstract
Background
Dysregulated activation of the inflammasome is involved in various human diseases including acute cerebral ischemia, multiple sclerosis and sepsis. Though many inflammasome inhibitors targeting NOD-like receptor protein 3 (NLRP3) have been designed and developed, none of the inhibitors are clinically available. Growing evidence suggests that targeting apoptosis-associated speck-like protein containing a CARD (ASC), the oligomerization of which is the key event for the assembly of inflammasome, may be another promising therapeutic strategy. Lonidamine (LND), a small-molecule inhibitor of glycolysis used as an antineoplastic drug, has been evidenced to have anti-inflammation effects. However, its anti-inflammatory mechanism is still largely unknown.

Methods
Middle cerebral artery occlusion (MCAO), experimental autoimmune encephalomyelitis (EAE) and LPS-induced sepsis mice models were constructed to investigate the therapeutic and anti-inflammasome effects of LND. The inhibition of inflammasome activation and ASC oligomerization by LND was evaluated using western blot (WB), immunofluorescence (IF), quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) in murine bone marrow-derived macrophages (BMDMs). Direct binding of LND with ASC was assessed using molecular mock docking, surface plasmon resonance (SPR), and drug affinity responsive target stability (DARTS).

Results
Here, we find that LND strongly attenuates the inflammatory injury in experimental models of inflammasome-associated diseases including autoimmune disease-multiple sclerosis (MS), ischemic stroke and sepsis. Moreover, LND blocks diverse types of inflammasome activation independent of its known targets including hexokinase 2 (HK2). We further reveal that LND directly binds to the inflammasome ligand ASC and inhibits its oligomerization.

Conclusions
Taken together, our results identify LND as a broad-spectrum inflammasome inhibitor by directly targeting ASC, providing a novel candidate drug for the treatment of inflammasome-driven diseases in clinic.
Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report
Authors: Liu Qingyue , Wang Zhiyu , Yu Chaoran , Zhu Jianping , Liu Chengli , Li Xiangsheng , Ren Li , Li Teng 
Published: December 2022

Abstract
Background
Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN).

Case presentation
We herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification.

Conclusion
To our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.
Feasibility of linac-based fractionated stereotactic radiotherapy and stereotactic radiosurgery for patients with up to ten brain metastases
Authors: Hirata Masanori , Yasui Kazuaki , Oota Naofumi , Ogawa Hirofumi , Onoe Tsuyoshi , Maki Sayo , Ito Yusuke , Hayashi Kenji , Asakura Hirofumi , Murayama Shigeyuki , Mitsuya Koichi , Deguchi Shoichi , Nakamura Katsumasa , Hayashi Nakamasa , Nishimura Tetsuo , Harada Hideyuki 
Published: December 2022

Abstract
Background
Linac-based fractionated stereotactic radiotherapy (fSRT) and stereotactic radiosurgery (SRS) are increasingly being used to manage patients with multiple metastases. This retrospective cohort study aimed to compare the outcomes after linac-based fSRT and SRS between three patient groups classified based on the number of brain metastases (BMs): 1 BM, 2–4 BM, 5–10 BM.

Methods
The data of consecutive patients with 1–10 BMs treated with fSRT or SRS between July 2016 and June 2018 at a single institution were collected. Patients with previous whole-brain radiotherapy (WBRT), concurrent use of WBRT, or surgical resection were excluded from the analysis. A total of 176 patients were classified into three groups according to the number of BMs: 78, 67, and 31 patients in 1 BM, 2–4 BM, and 5–10 BM, respectively. The Kaplan–Meier method was used to estimate overall survival (OS) curves, and the cumulative incidence with competing risks was used to estimate local control (LC), distant intracranial failure (DIF), and radiation necrosis (RN).

Results
Median OS was 19.8 months (95% confidence interval [CI] 10.2–27.5), 7.3 months (4.9–11.1), and 5.1 months (4.0–9.0) in 1 BM, 2–4 BM, and 5–10 BM, respectively. Compared to 2–4 BM, 1 BM had significantly better OS (hazard ratio [HR] 0.59, 95% CI 0.40–0.87; p = 0.0075); however, 5–10 BM had comparable OS (HR 1.36, 95% CI 0.85–2.19; p = 0.199). There was no significant difference in LC, DIF, and RN between tumor number groups, but DIF was lower in 1 BM. RN of grade 2 or higher occurred in 21 patients (13.5%); grade 4 and 5 RN were not observed.

Conclusions
The linac-based fSRT and SRS for patients with 5–10 BMs is comparable to that for patients with 2–4 BMs in OS, LC, DIF, and RN. It seems reasonable to use linac-based fSRT and SRS in patients with 5–10 BMs.
Single coronary ostium with obstructive hypertrophic cardiomyopathy treated using the Morrow procedure: a case report
Authors: Lv Xin , Li Jianhua , Liu Chuanzhen , Wei Ruyuan , Meng Lingwei , Kong Xiangjin , Wei Kaiming , Cao Guangqing , Liu Kai 
Published: December 2022

Abstract
Background
Hypertrophic cardiomyopathy is a commonly inherited heart disease. In addition, single coronary artery (SCA) is a rare
congenital anomaly of the coronary arteries. And SCA concomitant with severe
hypertrophic obstructive cardiomyopathy (HOCM) has seldom
been reported in the literature. However, such cases
have not been reported to be treated with the Morrow procedure.

Case presentation
Herein, we presented a case of a 64-year-old female diagnosed with a single left coronary artery with severe HOCM. The HOCM was treated with the Morrow procedure. The patient was discharged on the seventh postoperative day and was asymptomatic during the follow-up.

Conclusion
To our knowledge, this is the first study reporting a single left coronary artery with severe HOCM treated with the Morrow procedure. In addition, myocardial protection by cardioplegia antegrade perfusion was safe for the patient with SCA and HOCM.
Effect of ginsenoside compound K on alleviating colitis via modulating gut microbiota
Authors: Wang Li , Shao Li , Chen Man-Yun , Wang Lin , Zhang Wei , Tan Feng-Bo , Huang Wei-Hua 
Published: December 2022

Abstract
Background
Ginsenoside compound K (GC-K) potentially alleviates ulcerative colitis involved in gut microbiota, which is significantly associated with the occurrence and development of colitis. However, the effect and mechanism of GC-K on anti-colitis in relation to gut microbiota are not clear. This study focused on the prevention and mechanism of GC-K on Dextran sulfate sodium (DSS)-induced colitis of mice pertinent to gut microbiota.

Methods
DSS was used to establish a chronic colitis mouse model. Body weight analysis, colon length measurement, HE staining, and inflammatory factors levels were processed in animal experiments. Flow cytometry was employed to analyze Th17/Treg cells in the mouse spleen and blood. 16S rRNA sequencing was utilized to analyze gut microbiota. Fecal microbiota transplantation (FMT) experiment was employed to verify the anti-colitis efficacy of GC-K by reshaping gut microbiota.

Results
GC-K significantly relieved colitis-related symptoms due to decreased disease activity index (DAI) scores, spleen weight, and increased colon length. Additionally, the tight junction proteins were increased, and the pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β and IL-17, were decreased after GC-K treatment. Furthermore, Bacteroides spp. significantly increased after modeling. Moreover, FMT experiments confirmed that GC-K-driven gut microbiota greatly relieved DSS-induced colitis.

Conclusion
GC-K alleviated colitis via the modulation of gut microbiota.

Graphical Abstract
Ovarian tissue transplantation ameliorates osteoporosis and dyslipidaemia in ovariectomised mice
Authors: Zhou Encheng , Xiang Du , Yu Bin , Yao Hanlin , Sun Chao , Wang Yanfeng 
Published: December 2022

Abstract
Background
Ovarian insufficiency frequently renders postmenopausal women susceptible to osteoporosis and dyslipidaemia. Postmenopausal transplant women are at a higher risk developing osteoporosis and dyslipidaemia due to the concomitant application of glucocorticoids and immunosuppressants after solid organ transplantation. Thus, this study aimed to explore the feasibility of ovarian tissue transplantation (OTT) as an alternative to Hormone replacement therapy (HRT) for postmenopausal women with solid organ transplant needs.

Results
Sixty mice were randomly divided into four groups: sham operation, ovariectomised (OVX group), ovariectomy plus oestrogen (E2 group), and ovariectomy plus OTT (OTT group). The inhibin levels in the OTT group were increased and the follicle stimulating hormone and luteinizing hormone were suppressed to normal levels, which could not be achieved in the E2 group. The femoral bone mineral density in the OTT group was significantly increased than the E2 group (P < 0.05), and the probability of fracture was reduced by 1.4–2.6 times. Additionally, the high-density lipoprotein cholesterol levels were higher in the OTT group than in the E2 group and the triglyceride levels were lower in the OTT group than in the E2 group (P < 0.05).

Conclusion
OTT not only achieves certain endocrine effects by participating in the regulation of the hypothalamic-pituitary-ovarian feedback control loop, but also ameliorates osteoporosis and dyslipidaemia, which may be an alternative to traditional HRT for postmenopausal women with solid organ transplant needs.
Application of Pender’s health promotion model for type 2 diabetes treatment adherence: protocol for a mixed methods study in southern Iran
Authors: Shahabi Nahid , Hosseini Zahra , Aghamolaei Teamur , Ghanbarnejad Amin , Behzad Ahmad 
Published: December 2022

Abstract
Background
Type 2 diabetes (T2D) mellitus treatment as a chronic disease requires adequate adherence to treatment including controlling blood glucose levels and lifestyle management. The aim of this study is to investigate the factors affecting of adherence to T2D treatment from the perspective of patients and design an intervention program based on Pender’s health promotion model (HPM) to increase T2D treatment adherence in Bandar Abbas, a city located in the south of Iran.

Methods
This mixed method study will consist of qualitative stage, questionnaire design and a randomized, open-label, parallel-group interventional study based on HPM in southern Iran. Sampling for qualitative stage will continue until reaching the saturation. In the intervention stage, participants will be 166 T2D patients referring to the Bandar Abbas Diabetes Clinic will be randomized into intervention and control groups (allocation 1:1). After identifying the factors affecting adherence to treatment in T2D patients by qualitative study and literature review, a questionnaire based on HPM will be designed. In the next stage, 10 sessions of intervention for the intervention group will be designed. To evaluate the effect of the intervention, intervention and control groups will be tested for hemoglobin A1c (HbA1c) before and 3 months after the intervention.

Discussion
This designed study is a program for improving treatment adherence in T2D based on the HPM model and contributes to a better understanding of effective factors in adherence to treatment in T2D patients. The results of this project can be used for macro-diabetic planning.

Trial registration
This study is registered on the Iranian Registry of Clinical Trials (IRCT20211228053558N1: https://www.irct.ir/trial/61741) and first release date of 17th March 2022.
Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort
Authors: Noro Fabrizia , Santonastaso Federica , Marotta Annalisa , Bonaccio Marialaura , Orlandi Sabatino , Tirozzi Alfonsina , Costanzo Simona , De Curtis Amalia , Gianfagna Francesco , Di Castelnuovo Augusto , Brighenti Furio , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia , Gialluisi Alessandro , Izzi Benedetta ,   for the Moli-sani Study Investigators, Iacoviello Licia , de Gaetano Giovanni , Donati Maria Benedetta , Bonaccio Marialaura , Bonanni Americo , Cerletti Chiara , Costanzo Simona , De Curtis Amalia , Di Castelnuovo Augusto , Gialluisi Alessandro , Gianfagna Francesco , Persichillo Mariarosaria , Di Prospero Teresa , Vermylen Jos , Pegoraro Renzo , Spagnolo Antonio , Assanelli Deodato , Rago Livia , Costanzo Simona , Olivieri Marco , Panzera Teresa , Di Castelnuovo Augusto , Bonaccio Marialaura , Costanzo Simona , Esposito Simona , Gialluisi Alessandro , Gianfagna Francesco , Orlandi Sabatino , Ruggiero Emilia , Tirozzi Alfonsina , De Curtis Amalia , Magnacca Sara , Noro Fabrizia , Tirozzi Alfonsina , Persichillo Mariarosaria , Bracone Francesca , Panzera Teresa , Bonanni Americo 
Published: December 2022

AbstractBackgroundHigh dietary glycaemic index (GI) and load (GL) have been associated with increased risk of various cardiometabolic conditions. Among the molecular potential mechanisms underlying this relationship, DNA methylation has been studied, but a direct link between high GI and/or GL of diet and global DNA methylation levels has not been proved yet. We analyzed the associations between GI and GL and global DNA methylation patterns within an Italian population.ResultsGenomic DNA methylation (5mC) and hydroxymethylation (5hmC) levels were measured in 1080 buffy coat samples from participants of the Moli-sani study (mean(SD) = 54.9(11.5) years; 52% women) via ELISA. A 188-item Food Frequency Questionnaire was used to assess food intake and dietary GI and GL for each participant were calculated. Multiple linear regressions were used to investigate the associations between dietary GI and GL and global 5mC and 5hmC levels, as well as the proportion of effect explained by metabolic and inflammatory markers. We found negative associations of GI with both 5mC (β(SE) = − 0.073 (0.027),p = 0.007) and 5hmC (− 0.084 (0.030),p = 0.006), and of GL with 5mC (− 0.14 (0.060),p = 0.014). Circulating biomarkers did not explain the above-mentioned associations. Gender interaction analyses revealed a significant association of the gender-x-GL interaction with 5mC levels, with men showing an inverse association three times as negative as in women (interactionβ(SE) = − 0.16 (0.06),p = 0.005).ConclusionsOur findings suggest that global DNA methylation and hydroxymethylation patterns represent a biomarker of carbohydrate intake. Based on the differential association of GL with 5mC between men and women, further gender-based separate approaches are warranted.