Miracle-dz/UniFAR-FTUs huggingface dataset:
Copper-Binding Peptides Attenuate Microglia Inflammation Through Suppression of NF-kB Pathway.

SCOPE Activation of microglia, the resident immune cells of the central nervous system, has been related to the etiology and progression of neurodegenerative diseases; thus, finding novel approaches to suppress the neuroinflammatory process is of utmost relevance. METHODS AND RESULTS The anti-inflammatory activity of whey Cu-, Fe-, and Zn-binding peptides and their possible underlying mechanism of action were evaluated in microglia. Whey metal-binding peptides decreased nitric oxide production and TNF-α at mRNA and protein levels by stimulated BV-2 microglia in comparison to the control with no peptide treatment. The hydrophobicity, specific sequences, and possible synergistic effects seem to play a role. Cu-binding peptides (Cu-bp) presented anti-inflammatory activity both in BV-2 and primary microglia cultures. These peptides exert their action by suppressing NF-kB pathway since nuclear translocation of NF-kB p65 was decreased by roughly 30% upon Cu-bp treatment. Specific sequences identified in Cu-bp showed high affinity to bind NF-kB p65 by molecular docking (up to -8.8 kcal/mol), corroborating the immunofluorescence studies. CONCLUSION Cu-bp represent food-derived peptides that may be useful for neuroprotective purposes. Chelation of copper excess in the CNS and the bioavailability of such peptides, as well as their behavior in in vivo models, deserve further research for future applications. This article is protected by copyright. All rights reserved.
Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates

Background Venous blood drained from the knee joint after total knee arthroplasty (TKA) using a hemovac line is a potential source of bone marrow components, including stem cells, from the cutting surface of cancellous bones of the knee joint. However, the function of mesenchymal stem cells (MSCs) in patients with osteoarthritis (OA-MSCs) can be disrupted by inflammation of the joint. Further, to override the invasive nature of the currently used methods to obtain stem cells, their functional modification is necessary for therapeutic applications. Methods The effects of signal transducer and activator of transcription 3 (STAT3) signaling suppression on MSCs (iSTAT3-MSCs) were evaluated by comparative analyses of the characteristics of OA-MSCs and iSTAT3-MSCs from 20 patients who underwent TKA. Results OA-MSCs and iSTAT3-MSCs were adherent, with fibroblast-like appearance and high rates of expression of MSC-specific markers, including CD73, CD90, and CD105 (>90%). Both OA-MSCs and iSTAT3-MSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic cells; however, iSTAT3-MSCs showed higher levels of osteogenic and chondrogenic differentiation markers than OA-MSCs. Additionally, the anti-inflammatory and chondroprotective cytokine levels were higher in iSTAT3-MSCs than in OA-MSCs. Conclusions These findings indicate that iSTAT3-MSCs after TKA are potentially effective for stem cell therapy in the context of bone and cartilage disorders.
Exploring the association between social behaviour, trust, and its neural correlates in first episode psychosis patients and in individuals at clinical high risk for psychosis

Objectives Psychosis is characterized by paranoid delusions, social withdrawal, and distrust towards others. Trust is essential for successful social interactions. It remains unknown which aspects of social functioning are associated with reduced trust in psychosis. Therefore, we investigated the association between social behaviour, trust, and its neural correlates in a group of individuals with psychotic symptoms (PS‐group), consisting of first episode psychosis patients combined with individuals at clinical high risk. Methods We compared 24 PS individuals and 25 healthy controls. Affect and social withdrawal were assessed using the Experience Sampling Method. Trust was measured during functional magnetic resonance imaging (fMRI) scanning, using a trust game with a cooperative and unfair counterpart. Results The PS‐group showed lower baseline trust compared to controls and reported less positive and more negative general affect. Social withdrawal did not differ between the groups. Social withdrawal and social reactivity in affect (i.e., changes in affect when with others compared to when alone) were not associated with trust. On the neural level, in controls but not in the PS‐group, social withdrawal was associated with caudate activation during interactions with an unfair partner. An increase in positive social reactivity, was associated with reduced insula activation in the whole sample. Conclusions Social withdrawal and social reactivity were not associated with reduced initial trust in the PS‐group. Like controls, the PS‐group showed a positive response in affect when with others, suggesting a decrease in emotional distress. Supporting patients to keep engaging in social interactions, may alleviate their emotional distress. Practitioner points Individuals with psychotic symptoms show reduced initial trust towards unknown others. Trust in others is not associated with social withdrawal and reported affect when with others, nor when alone. Like controls, individuals with psychotic symptoms showed reduced negative affect and increased positive affect when with others compared to when alone. We emphasize to support individuals with psychotic symptoms to keep engaging in social interactions, given it may reduce social withdrawal and alleviate their emotional distress.
The emerging therapeutic potential of extracellular vesicles in trauma

Traumatic injury is a major cause of morbidity and mortality worldwide, despite significant advances in treatments. Most deaths occur either very early, through massive head trauma/CNS injury or exsanguination (despite advances in transfusion medicine), or later after injury often through multiple organ failure and secondary infection. Extracellular vesicles (EVs) are known to increase in the circulation after trauma and have been used to limited extent as diagnostic and prognostic markers. More intriguingly, EVs are now being investigated as both causes of pathologies post trauma, such as trauma‐induced coagulopathy, and as potential treatments. In this review, we highlight what is currently known about the role and effects of EVs in various aspects of trauma, as well as exploring current literature from investigators who have begun to use EVs therapeutically to alter the physiology and pathology of traumatic insults. The potential effectiveness of using EVs therapeutically in trauma is supported by a large number of experimental studies, but there is still some way to go before we understand the complex effects of EVs in what is already a complex disease process.
High heritability of telomere length and low heritability of telomere shortening in wild birds

Telomere length and telomere shortening predict survival in many organisms. This raises the question of the contribution of genetic and environmental effects to variation in these traits, which is still poorly known, particularly for telomere shortening. We used experimental (cross‐fostering) and statistical (quantitative genetic “animal models”) means to disentangle and estimate genetic and environmental contributions to telomere length variation in pedigreed free‐living jackdaws (Corvus monedula). Telomere length was measured twice in nestlings, at ages 4 (n = 715) and 29 days (n = 474), using telomere restriction fragment (TRF) analysis, adapted to exclude interstitial telomeric sequences. Telomere length shortened significantly over the nestling period (10.4 ± 0.3 bp day–1) and was highly phenotypically (rP = 0.95 ± 0.01) and genetically (rG > 0.99 ± 0.01) correlated within individuals. Additive genetic effects explained a major part of telomere length variation among individuals, with its heritability estimated at h2 = 0.74 on average. We note that TRF‐based studies reported higher heritabilities than qPCR‐based studies, and we discuss possible explanations. Parent–offspring regressions yielded similar heritability estimates for mothers and fathers when accounting for changes in paternal telomere length over life. Year effects explained a small but significant part of telomere length variation. Heritable variation for telomere shortening was low (h2 = 0.09 ± 0.11). The difference in heritability between telomere length (high) and telomere shortening (low) agrees with evolutionary theory, in that telomere shortening has stronger fitness consequences in this population. Despite the high heritability of telomere length, its evolvability, which scales the additive genetic variance by mean telomere length, was on average 0.48%. Hence, evolutionary change of telomere length due to selection is likely to be slow.
Abdominal Wall Expanding System. Intraoperative Abdominal Wall Expansion as a Technique to Repair Giant Incisional Hernia and Laparostoma. New and Long-Term Results From a Three-Center Feasibility Study

Background The abdominal wall expanding system (AWEX) was first applied in 2012 and published in 2017. This novel technique was developed to reconstruct complex incisional hernias and residual skin-grafted laparostoma after treatment of an open abdomen, when primary midline closure was impossible. The main aim was the anatomical reconstruction of the abdominal wall and the avoidance of dissecting techniques (component separation). Methods Between 2012 and 2019, 33 patients underwent AWEX hernia repair in three certified hernia centers. The retracted abdominal wall was stretched with the AWEX system intraoperatively for approximately 30 min. Hernia size was measured preoperatively, on CT, and intraoperatively. The gain in length on the lateral abdominal wall (decrease in width of the defect) after stretching and any residual midline gap were determined in the OR. Results 33 patients underwent AWEX procedures. Six cases were evaluated separately because of additional procedures (TAR, four cases) and preoperative application of botulinum toxin (two cases). The median (95% confidence interval) measured width of hernia defects was 13 (12–16) cm, the median gain in length on the lateral abdominal wall was 12 (10–15) cm. After median follow-up of 29 (12–54) months, one recurrence from the broken mesh was observed. No method-related complications occurred. Conclusion Based on the 2017 and current results, the AWEX system represents an alternative or supplemental procedure to current techniques for complex abdominal wall reconstruction. The system proved again to be time-saving, safe, effective, and easy to learn. Further studies with enhanced technology are in progress.
Adipose-derived stem cells (ADSCs) inhibit the expression of anti-apoptosis proteins through up-regulation of ATF4 on breast cancer cells

Background While current basic studies indicate adipose-derived stem cells (ADSCs) can promote cell proliferation, clinical trials have shown no significant difference in breast cancer recurrence rates for patients with or without autologous fat grafting (AFG). In this study we attempted to explore the underlying mechanism for these contradictory results. Methods ADSCs and umbilical mesenchymal stem cells (UMSCs) were co-cultured with breast cancer cells (MCF-7 and MDA-MB-231), and the cell viability analyzed by CCK-8 cell proliferation assay, TUNEL assay and immunofluorescence assay. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) experiments and Western blot analysis were used to detect the mRNA and protein expression of activating transcription factor 4 (ATF4) and its downstream gene (MCL1 & BCL2), respectively. Results Co-cultured ADSCs could promote cell proliferation and cell apoptosis, and up-regulate ATF4 expression both in MCF-7 and MDA-MB-231. While co-cultured UMSCs could only promote cell apoptosis in MCF-7. Interestingly, we found that when co-cultured ADSCs, the expression of MCL1 and BCL2 protein was decreased, even if their mRNA expression was up-regulated both in MCF-7 and MDA-MB-231. Conclusions Co-cultured ADSCs can up-regulate ATF4 expression, then interfere with the translation process of MCL1 and BCL2 mRNA and induce cell apoptosis. These data provide insight into the safety characteristics of AFG.
Multisystem Inflammatory Syndrome in Children Presenting With Pseudotumor Cerebri and a Review of the Literature

Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening inflammatory immune response associated with severe acute respiratory syndrome coronavirus 2 infection. The majority of patients have been presented with hypotension, shock, gastrointestinal, cardiovascular and mucocutaneous symptoms. The incidence of neurologic symptoms in MIS-C is of rising concern as they are not well described and reported in fewer patients. An 8-year-old boy was admitted to the hospital with headache, fever, conjunctivitis, and hyperinflammatory findings diagnosed as MIS-C. Fundus examination performed with complaints of headache, vomiting, and conjunctivitis showed bilateral papilledema. Pseudotumor cerebri is a rare manifestation of MIS-C that can lead to vision loss and may not only be resolved with the standard treatment for MIS-C. We report a case of MIS-C presented with neurologic symptoms due to pseudotumor cerebri and successfully treated with intravenous immunoglobulin and acetazolamide.
Antimicrobial peptide activity in asymmetric bacterial membrane mimics

We report on the response of asymmetric lipid membranes composed of palmitoyl oleoyl phosphatidylethanolamine and palmitoyl oleoyl phosphatidylglycerol, to interactions with the frog peptides L18W-PGLa and magainin 2 (MG2a), as well as the lactoferricin derivative LF11-215. In particular we determined the peptide-induced lipid flip-flop, as well as membrane partitioning of L18W-PGLa and LF11-215, and vesicle dye-leakage induced by L18W-PGLa. The ability of L18W-PGLa and MG2a to translocate through the membrane appears to correlate with the observed lipid flip-flop, which occurred at the fastest rate for L18W-PGLa. The higher structural flexibility of LF11-215 in turn allows this peptide to insert into the bilayers without detectable changes of membrane asymmetry. The increased vulnerability of asymmetric membranes to L18W-PGLa in terms of permeability, appears to be a consequence of tension differences between the compositionally distinct leaflets, but not due to increased peptide partitioning.
Increased phosphorylated CREB1 protein correlates with poor prognosis in clear cell renal cell carcinoma

Background This study aims to investigate the level of cAMP response element-binding protein 1 (phospho S133) (p-CREB1) protein in clear cell renal cell carcinoma (ccRCC) and evaluates its prognosis significance. Methods Immunohistochemistry (IHC) method was performed to detect p-CREB1 staining in 233 ccRCC patients. Three or more high-power fields per tissue section were equally captured by a Leica DMRXA microphotographic system, and average staining intensity (optical density, OD) was analyzed by Leica Qwin Standard V2.6 system. Univariate and multivariate Cox proportional regression model was performed to assess the correlation of p-CREB1 staining and clinical outcomes. Results IHC proved that the level of p-CREB1 protein was significantly higher in tumor tissues than in adjacent normal tissues, and gradually increased from normal to tumor sections. On the basis of the receiver operating characteristic curve, patients were divided into low p-CREB1 staining (OD ≤0.28) and high p-CREB1 staining subgroup (OD >0.28) according to p-CREB1 protein staining intensity of tumor cells. Multivariate analyses showed that high p-CREB1staining was an independent risk factor for cancer-specific free survival, overall survival and progression-free survival. Conclusions p-CREB1 protein is an independent prognostic biomarker for ccRCC patients.
Clinical value of lymph node dissection for stage T1b mid-thoracic esophageal squamous cell carcinoma.

Background Surgery remains the mainstay of treatment for esophageal squamous cell carcinoma (ESCC), during which lymph node (LN) dissection, especially recurrent laryngeal nerve (RLN) LN dissection, is particularly important and challenging. This study aimed to investigate the LN metastasis of stage T1b mid-thoracic ESCC and explore the clinical value of RLN LN dissection. Methods The clinicopathological data of 254 patients with stage T1b mid-thoracic ESCC who underwent the McKeown procedure ("tri-incisional esophagectomy") and three-field LN dissection (3FD) at Fujian Cancer Hospital from January 2010 to December 2015 were retrospectively analyzed. The value of LN dissection (especially RLN LNs) was evaluated by calculating the metastasis rate of each LN station. The efficacy index (EI) of the dissection was calculated by multiplying the frequency (%) of metastases to a station and the 5-year survival rate (%) of patients with metastases to that station, and then dividing by 100. Results The stage T1b mid-thoracic ESCC had the highest rate of metastasis in the paracardiac LNs (4.3%), followed by RLN LNs (2.8%) and the left gastric artery LNs (2.8%). The 5-year survival rate was highest in patients who received lesser gastric curvature LN dissection (100%), followed by patients who underwent right RLN LN dissection (80%), and was 50% in patients who had undergone dissection of the left RLN LNs, upper paraesophageal LNs, subcarinal LNs, and left gastric artery LNs, respectively. In addition, dissection of the right RLN LNs had the highest EI value (2.2), followed by the dissection of LNs along the lesser curvature of the stomach (1.6) and left gastric artery LNs (1.4). Conclusions Right RLN LNs have a metastasis rate only lower than that of the paracardiac LNs, but could be the most valuable location for performing dissection.
Predicted outcomes of subdividing M1-stage metastatic lung cancer based on the prognosis and the response to local consolidative therapy

Background For stage IV non-small cell lung cancer (NSCLC) patients, systemic therapy is the main strategy, and local consolidative therapy tends to be performed for patients with oligometastases. The porpose of this article is to evaluate the prognostic effects of local consolidative therapy for patients with stage IV NSCLC and divide these patients into different subcategories to stratify the prognoses. Methods A total of 30,583 patients with stage IV NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. To identify factors related to high cancer-specific mortality (CSM) rates and compare the prognostic effects of different treatment strategies, a competing risk model was developed. Furthermore, independent prognostic factors identified through multivariable analysis were employed to supplement the current M1 subcategory. Cumulative incidence curves were estimated using the Kaplan-Meier method, and the log-rank test was used to compare prognostic differences. Results The CSM rates of M1a, M1b, and M1c patients were significantly different [M1b versus M1a: subdistribution hazard ratio (SHR), 1.38; 95% confidence interval (CI), 1.31–1.45; P<0.001; M1c vs. M1a: SHR, 1.76; 95% CI, 1.67–1.85; P<0.001]. Patients were divided into five groups depending on the M1 subcategory and liver involvement (Group A, M1c NSCLC with liver involvement; Group B, M1c NSCLC without liver involvement; Group C, M1b NSCLC with liver involvement; Group D, M1b NSCLC without liver involvement; and Group E, M1a NSCLC). Univariable analysis showed that liver involvement was associated with increased cancer-specific mortality (CSM) rates in both M1b and M1c patients (A vs. B: SHR, 1.36; 95% CI, 1.30–1.43; P<0.001; C vs. D: SHR, 1.27; 95% CI, 1.20–1.35; P<0.001). Primary tumor surgery plus chemotherapy may substantially benefit patients, especially M1b patients (surgery alone: SHR, 0.425; 95% CI, 0.361–0.500; P<0.001 vs. chemotherapy alone: SHR, 0.366; 95% CI, 0.352–0.382; P<0.001 vs. chemotherapy plus surgery: SHR, 0.194; 95% CI, 0.165–0.228; P<0.001; no treatment used as reference). Conclusions Subdivision of M1 disease and awareness of liver involvement may help to inform the prognosis of stage IV NSCLC patients and facilitate treatment planning.
Diagnostic biomarkers and potential drug targets for coronary artery disease as revealed by systematic analysis of lncRNA characteristics

Background The expression profile of lncRNAs in coronary artery disease (CAD) patients has not yet been fully explored. Therefore, the current study aimed to investigate lncRNA-based prognostic biomarkers for CAD. Methods The expression profiles of lncRNA and messenger RNA (mRNA) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNA (DElncRNAs) and DEmRNAs were identified from CAD and normal samples, and weighted gene co-expression network analysis (WGCNA) was conducted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the principal functions of significantly dysregulated genes. The potential drugs of new CAD-specific genes were identified by network distance method. Receiver operating characteristic (ROC) was used to verify the classification performance of genes. Results A total of 512 differentially expressed genes (DEGs) and 308 DElncRNAs were identified from GSE113079 dataset to classify CAD samples. Through WGCNA co-expression analysis, 24 co-expression modules were obtained. A total of 187 DElncRNAs and 253 DEGs were determined from 7 modules correlated with CAD. Functional enrichment analysis showed that these DEGs were mainly related to inflammatory and immune-related pathways. Furthermore, 36 regulatory pairs of significantly shared micro RNAs (miRNAs) were identified as dysregulated lncRNA-mRNA (LRM-CAD), which contained 11 lncRNAs and 33 genes. Compared with a single lncRNA or gene, LRM-CAD showed stronger classification performance [average area under the curve (AUC) =0.958]. We screened 3 potential therapeutic drugs, DB09105, DB12371, and DB12612, a by binding drug-target gene interaction network. Molecular docking verified that the S1PR1 gene bound relatively closely to DB12371 and DB12612. The ROC analysis on external data sets showed that S1PR1, AC012640.4, and S1PR1-AC012640.4 could effectively distinguish CAD samples from control samples. Conclusions We provided a transcriptome overview of abnormally expressed lncRNAs in CAD patients and identified novel biomarkers for diagnosing CAD.