Miracle-dz/UniFAR-FTUs huggingface dataset:
LRG1 Suppresses Migration and Invasion of Esophageal Squamous Cell Carcinoma by Modulating Epithelial to Mesenchymal Transition

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. The molecular pathogenesis underlying ESCC remains to be explored. Leucine-rich ɑ-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of various cancer types, however its role in ESCC is unknown. Materials and Methods: Data from the public database was analyzed to address the expression of LRG1 in ESCC. Gain-of-function studies were performed in select ESCC cell lines by over-expression or addition of recombinant LRG1, while loss-of-function studies achieved by small interfering RNA mediated knockdown. Wound healing and transwell assays were conducted to investigate ESCC cell migration and invasion upon manipulating LRG1 levels. Western blot and Immunofluorescence staining were used to examine the changes in epithelial to mesenchymal transition (EMT) and TGFβ signaling pathway. Results: LRG1 mRNA levels were found to be significantly down-regulated in patients with ESCC as well as in several ESCC cell lines. Silencing of LRG1 promoted, while overexpression of LRG1 inhibited ESCC cell migration and invasion. In line with this, Silencing of LRG1 enhanced, while overexpression of LRG1 reduced TGFβ signaling and EMT of ESCC cells. Conclusion/Significance: LRG1 suppresses ESCC cell migration and invasion via negative modulation of TGFβ signaling and EMT. Down-regulation of LRG1 in ESCC patients may favor tumor metastasis and disease progression.
miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.
Tumour-Infiltrating Immune Cell-Based Subtyping and Signature Gene Analysis in Breast Cancer Based on Gene Expression Profiles

Tumour-infiltrating immune cells have been indicated to play an important role in prognosis prediction and therapy sensitivity for breast cancer. In recent years, estimating the abundance of immune cells based on tumour transcriptome data has provided a novel way to analyse the clinical significance of various immune cell subsets. This study integrated breast cancer tissue transcriptome datasets from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. A novel breast cancer immunotyping and a new prognostic model based on tumour-infiltrating immune cell subsets have been established, aiming to provide new clues regarding prognostic prediction and precision therapy for breast cancer. The key differentially expressed gene between different breast cancer immunotypes has also been identified. We performed unsupervised clustering analysis and construct a novel immunotyping which could classify breast cancer cases into immunotype A (B_cellhigh NKhigh CD8+_Thigh CD4+_memory_T_activatedhigh γδTlow Mast_cell_activatedlow Neutrophillow) and immunotype B (B_celllow NKlow CD8+_Tlow CD4+_memory_T_activatedlow γδThigh Mast_cell_activatedhigh Neutrophilhigh) in luminal B, HER2-enriched and basal-like subtypes. The 5-year (85.7% vs. 73.4%) and 10-year OS (75.60% vs. 61.73%) of immunotype A population were significantly higher than those of immunotype B. A novel tumour-infiltrating immune cell-based prognostic model had also been established and the result immunorisk score (IRS) could serve as a new prognostic factor for luminal B, HER2-enriched and basal-like breast cancer. The higher IRS was, the worse prognosis was. We further screened the differentially expressed genes between immunotype A and B and identified a novel breast cancer immune-related gene, prostaglandin D2 synthase (PTGDS) and higher PTGDS mRNA expression level was positively correlated with earlier TNM stage. Immune-related signaling pathways analysis and immune cell subsets correlation analysis revealed that PTGDS expression was related with abundance of B cells, CD4+ T cells and CD8+ T cells, which was finally validated by immunohistochemical and immunofluorescence staining. We established a novel immunotyping and a tumour-infiltrating immune cell-based prognostic prediction model in luminal B, HER2-enriched and basal-like breast cancer by analyzing the prognostic significance of multiple immune cell subsets. A novel breast cancer immune signature gene PTDGS was discovered, which might serve as a protective prognostic factor and play an important role in breast cancer development and lymphocyte-related immune response.
Prenylflavonoid Icariin Induces Estrogen Response Element–Independent Estrogenic Responses in a Tissue-Selective Manner

Abstract Icariin, a flavonoid phytoestrogen derived from Herba epimedii, has been reported to exert estrogenic effects in bone and activate phosphorylation of estrogen receptor (ER) α in osteoblastic cells. However, it is unclear whether icariin selectively exerts estrogenic activities in bone without inducing undesirable effects in other estrogen-sensitive tissues. The present study aimed to investigate the tissue-selective estrogenic activities of icariin in estrogen-sensitive tissues in vivo and in vitro. Long-term treatment with icariin effectively prevented bone of ovariectomized (OVX) rats from estrogen deficiency–induced osteoporotic changes in bone structure, bone mineral density, and trabecular properties. Moreover, icariin regulated the transcriptional events of estrogen-responsive genes related to bone remodeling and prevented dopaminergic neurons against OVX-induced changes by rescuing expression of estrogen-regulated tyrosine hydroxylase and dopamine transporter in the striatum. Unlike estrogen, icariin did not induce estrogenic effects in the uterus and breast in mature OVX rats or immature CD-1 mice. In vitro studies demonstrated that icariin exerted estrogen-like activities and regulated the expression of estrogen-responsive genes but did not induce estrogen response element–dependent luciferase activities in ER-positive cells. Our results support the hypothesis that icariin, through its distinct mechanism of actions in activating ER, selectively exerts estrogenic activities in different tissues and cell types.
Remote Ischaemic Preconditioning Reduces Kidney Injury Biomarkers in Patients Undergoing Open Surgical Lower Limb Revascularisation: A Randomised Trial

Background and Aims Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. Results Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p = 0.021, p = 0.021, p = 0.021, p = 0.021, p = 0.021, Conclusions Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.
The quality of acute intensive care and the incidence of critical events have an impact on health-related quality of life in survivors of the acute respiratory distress syndrome – a nationwide prospective multicenter observational study

Background: Initial treatment (ventilator settings, rescue therapy, supportive measures), and prevention of critical events improve survival in ARDS patients, but little data exists on its effect on health-related quality of life (HRQOL) and return to work (RtW) in survivors. We analyzed the association of the intensity of treatment at ARDS onset and the incidence of critical events on HRQOL and RtW a year after ICU discharge. Methods: In a prospective multi-centre cohort study, the intensity of treatment and the incidence of critical events were determined at 61 ICUs in Germany. At 3, 6, and 12 months, 396 survivors reported their HRQOL (Short-Form 12) and RtW. The parameters of the intensity of acute management (lung protective ventilation, prone position, hemodynamic stabilization, neuromuscular blocking agents), and critical events (hypoxemia, hypoglycemia, hypotension) were associated with HRQOL and RtW. Results: Patients ventilated at ARDS onset with a low tidal volume (VT≤7 ml/kg) had higher arterial carbon dioxide levels (PaCO2=57.5±17 mmHg) compared to patients ventilated with VT>7ml/kg (45.7±12, p=0.001). In a multivariate adjusted dichotomized analysis, a better mental 3-month SF-12 was observed in the higher VT-group (mean 43.1±12) compared to the lower VT-group (39.5±9, p=0.042), while a dichotomized analysis for driving pressures (≤14 mbar vs >14 mbar) did not show any difference neither in PaCO2 levels nor in HRQOL parameters. A decrease in the mental (6-month: 40.0±11 vs 44.8±13, p=0.038) and physical SF-12 (12-month: 38.3±11 vs 43.0±13, p=0.015) was reported from patients with hypoglycemia (blood glucose <70 mg/dl) compared to those without hypoglycemic episodes. More frequent vasopressor use with mean arterial pressure ≥65 mmHg was associated with an impaired physical SF-12 (6-month: 38.8±10) compared to less vasopressor use (43.0±11, p=0.019). Conclusions: In acute management of ARDS, a lower VT strategy associated with hypercapnia, as well as the frequent usage of catecholamines and the management of blood glucose may influence short-term HRQOL of survivors. The awareness of these findings is of clinical importance for the acute and post-ICU care.
Adverse Events after Uterine Compression Sutures for Postpartum Hemorrhage: Report of Three Cases and Review of the Literature

Uterine compression sutures may be life and fertility saving interventions in management of uterine atony. However, unintended long-term outcomes may occur and there is scarce literature about management. Herein, management of long-term adverse outcomes (synechia, pelvic pain and pelvic collection) of three different cases who had to be treated by uterine compression sutures is reported with review of the literature.
Agreement between self-reported psychoactive substance use and urine toxicology results for adults with opioid use disorder admitted to hospital

Abstract Hospitals often perform urine drug screens (UDS) upon inpatient admission to confirm self-reported psychoactive substance use for patients with opioid use disorder (OUD). We sought to evaluate the agreement between UDS and patient self-report for psychoactive substances detected with UDS for adults with OUD admitted to hospital. For 11 substance categories, we evaluated agreement between the UDS and the documented history over a 5-year period for consecutive adults admitted to one academic center with a history of OUD. Among the 153 patients, overall agreement across the 1683 different history/UDS pairs (i.e. either history+/UDS + or history-/UDS-) was high (81.3%) but varied (from lowest to highest) by substance [opiates (56.9%), benzodiazepines (66.0%), 6-acetylmorphine (67.3%), cocaine (81.0%), cannabinoids (81.0%), methadone (83.7%), buprenorphine (85.0%), amphetamine (94.8%), barbiturates (95.4%), and phencyclidine (98.7%)]. History+/UDS- pair mismatches were most frequent for 6-acetylmorphine (32.7%), methadone (14.3%) and oxycodone (12.4%); history-/UDS + pair mismatches were most frequent for opiates (43.1%), benzodiazepines (24.8%) and cannabinoids (18.3%). The change in agreement over time of self-reported heroin use may reflect an increasing number of patients unknowingly using illicit fentanyl products. Among hospitalized patients with OUD, agreement between reported psychoactive substance use history and UDS results is strong with the exception of opiates, heroin, and benzodiazepines.
Psychosocial Profile and Quality of Life in Children with Bronchial Asthma; A Comparative Study of Self Reports and Parent Proxy Reports of Peds Ql™ Inventory

Background : Health-related quality of life (HRQL) is classically defined as “the functional effects of a disease and of its ensuing therapy on a patient as perceived by the patient himself”. It is crucial to be considered in management of chronic diseases; asthma included. Objectives : Evaluation of the psychosocial profile and caregivers'perception compared to children's perception of HRQL of an Egyptian sample of children with bronchial asthma Methodology: The current case control study comprised 8-12 years old 40 Egyptian children and their caregivers (their mothers); 20 known asthmatics of both sexes as Group Iand 20 clinically physically healthy children of comparable age and sex and their caregivers (their mothers) as controls (group II). Full clinical assessment, pulmonary function testing, psychometric evaluation, and assessment of Pediatric Quality of Life using an Arabic validated version of PedsQL™ Inventory both Child Self Report and Parent Proxy Report were carried out for all enrolled children. Results : Total HRQOL score and all its sub-scores(both child and parental reports) were significantly lower in asthmatics compared to controls. HRQOL total score was negatively correlated with anxiety and depression scores and positively correlated with FEV1 and FEF 25%-75%. Moreover, caregivers reported significantly lower scores of the total HRQOL as well as its all assessed sub-scales compared to their asthmatic childrenself reports. Conclusion: childhood asthma has lead to significant lowering of the total HRQOL and all its sub scales in the studied Egyptian sample of asthmatic children withworse caregivers' perception compared to their asthmatic children's perception.
Value in buyer-supplier relationships: the impact of relational purchasing practices

This study investigates the role of relational purchasing practices and supplier capabilities in the creation of relationship value. A survey study receiving 662 responses is conducted. The survey respondents are suppliers’ contact persons in the key supplier relationships of four large buyer companies. The results add to the earlier literature by giving support to and clarifying the importance of supplier’s integration with customer in relationship value creation. The study also contributes by identifying that a supplier’s provision of measurement information on its products and their delivery has a positive impact on relationship value. Acknowledgements: Authors are thankful for the financial support of the Finnish Funding Agency for Innovation and the companies participating in the project “Value Creating Procurement”.
Study of the efficacy of prostaglandins and prostacyclin in decrease of osmotic permeability of the frog urinary bladder

Washout of autacoids using a repeated change of serosal Ringer solution of the frog urinary bladder was accompanied by a pronounced rise in the osmotic water permeability. A decrease in the osmotic water permeability was achieved by addition at the serosal Ringer solution of different eikosanoids at concentrations of 10(-10)-10(-6) M. According to efficiency of the recovery of the low osmotic water permeability, the substances studied showed the following order: prostaglandin E1 > prostaglandin > E2 > prostaglandin F2 alpha > (prostaglandin I2). The data obtained indicate a role of the endogenous prostaglandin production in maintaining of the low osmotic water permeability.
Factors affecting knowledge about the adult guardianship and civil trust systems: evidence from Japan

ABSTRACT This study examines the socio-economic factors influencing public awareness of the adult guardianship and civil trust systems in Japan. The results of this study show that financial literacy is the most influential factor affecting knowledge of the adult guardianship and civil trust systems. Gender, age, living alone, income, and assets are also found to be related to knowledge about these systems, but they are not consistent. We argue that policy makers should emphasize financial literacy and conduct targeted promotion campaigns to help those living with dementia to continue to participate in and benefit from economic activities.
The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.
Histone Acetylation at the Promoter for the Transcription Factor PuWRKY31 Affects Sucrose Accumulation in Pear Fruit1[OPEN]

High acetylation in the promoter of a transcription factor gene is associated with sucrose accumulation in pear fruit by activating the expression of a sucrose transport gene. Sugar content is an important trait of fleshy fruit, and elevating Suc levels is a major goal in horticultural crop breeding. Here, we examined the sugar content in two varieties of the Ussurian pear (Pyrus ussuriensis), ‘Nanguo’ (NG) and its bud sport (BNG), and we found that Suc content was higher in BNG fruit than in NG fruit. We compared the transcriptomes of the two varieties using RNA sequencing and identified a SWEET (Sugars Will Eventually be Exported Transporter) gene, PuSWEET15, expressed at higher levels in BNG fruit. Heterologous expression of PuSWEET15 in a SUSY7/ura yeast (Saccharomyces cerevisiae) strain showed that PuSWEET15 is an active Suc transporter. Overexpression of PuSWEET15 in NG pear fruit increased Suc content, while silencing of PuSWEET15 in BNG fruit decreased Suc content. The WRKY transcription factor PuWRKY31 was also expressed more highly in BNG fruit than in NG fruit, and we found that PuWRKY31 bound to the PuSWEET15 promoter and induced its transcription. The histone acetylation level of the PuWRKY31 promoter was higher in BNG fruit, suggesting a mechanism by which Suc levels can be elevated.
Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue

Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV], and fibrotic human lung tissue and evaluate whether their stiffness and viscoelastic properties were reflective of native tissue. For hydrogel generation, control, COPD GOLD IV, and fibrotic human lung tissues were decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Rheological properties from tissues and hydrogels were assessed with a low-load compression tester measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a greater stress relaxation than tissues. ECM hydrogels required three Maxwell elements with slightly faster relaxation times (τ) than that of native tissue, which required four elements. The relative importance (Ri) of the first Maxwell element contributed the most in ECM hydrogels, whereas for tissue the contribution was spread over all four elements. IPF tissue had a longer-lasting fourth element with a higher Ri than the other tissues, and IPF ECM hydrogels did require a fourth Maxwell element, in contrast to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue, while viscoelasticity differed.