Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing circular ANRIL protects HK-2 cells from lipopolysaccharide-induced inflammatory injury through up-regulating microRNA-9

Abstract Circular antisense non-coding RNA in the INK4 locus (cANRIL) participated in inflammation of endothelial cells. However, whether cANRIL is associated with inflammatory injury of HK-2 cells, thereby affecting chronic kidney disease has not been investigated. We tested the hypothesis that cANRIL participated in inflammatory response in vitro. HK-2 cells were stimulated by lipopolysaccharides (LPS). RT-qPCR was executed for cANRIL expression assessment. After transfection, cell viability, apoptosis, inflammatory cytokines and ROS generation were appraised to evaluate the impact of silencing cANRIL on LPS-induced inflammatory injury. The regulatory relationship between cANRIL and microRNA-9 (miR-9) was verified. In addition, whether miR-9 affected LPS-induced inflammatory injury was measured after miR-9 inhibitor transfection. Western blot was utilized to detect NF-κB and JNK/p38 pathway-related proteins. The results showed that LPS promoted cANRIL expression and cell injuries in HK-2 cells. Furthermore, silencing cANRIL alleviated inflammatory injuries by promoting viability, suppressing apoptosis, inflammatory cytokines and ROS generation in HK-2 cells. In addition, miR-9 expression was accelerated by silencing cANRIL. Meanwhile, miR-9 down-regulation invalidated the effect of silencing cANRIL on inflammation and NF-κB and JNK/p38 pathways. The study clarified that silencing cANRIL hindered NF-κB and JNK/p38 pathways by positively regulating miR-9, thereby protecting HK-2 cells from LPS-induced injury.
Adapted version of the Pubertal Development Scale for use in Brazil

ABSTRACT OBJECTIVE To determine whether scores in an adapted version of the self-assessment Pubertal Development Scale into Portuguese match those from the gold standard in pubertal development (Tanner scale). METHODS This was a cross-sectional study with a convenience sample of 133 children and adolescents aged nine to 17 years (59 males; mean age of 13 years and six months, with standard deviation = 25 months). Youngsters completed the Pubertal Development Scale and were then examined by specialists in adolescent medicine. RESULTS Exact absolute agreement of pubertal stages were modest, but significant associations between measures (correlation; intra-class correlation coefficients of consistency) showed that the Pubertal Development Scale adequately measures changes that map onto pubertal development determined by physical examination, on par with international publications. Furthermore, scores obtained from each Pubertal Development Scale question reflected adequate gonadal and adrenal events assessed by clinical ratings, mostly with medium/high effect sizes. Latent factors obtained from scores on all Pubertal Development Scale questions had excellent fit indices in Confirmatory Factor Analyses and correlated with Tanner staging. CONCLUSIONS We conclude that self-assessment of body changes by youngsters using the Portuguese version of the Pubertal Development Scale is useful when estimates of pubertal progression are sufficient, and exact agreement with clinical staging is not necessary. The Pubertal Development Scale is, therefore, a reliable instrument for use in large-scale studies in Brazil that aim at investigating adolescent health related to pubertal developmental. The translated version and scoring systems are provided.
RETRACTED ARTICLE: Downregulated long non-coding RNA LINC00899 inhibits invasion and migration of spinal ependymoma cells via RBL2-dependent FoxO pathway

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Qun-Bang Chen, Zhao-Hui Li, Yao Fu, Ning-Ning Lv, Nan Tian, Liang Han, and Yu Tian. Downregulated long non-coding RNA LINC00899 inhibits invasion and migration of spinal ependymoma cells via RBL2-dependent FoxO pathway. Cell Cycle. 2019;18(19):2566–2579. doi: 10.1080/15384101.2019. 1652046 Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide their original data. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
A comparative in silico analysis of Rab5 proteins from pathogenic species to find its role in the pathogenesis

The enteric protozoan parasite, Entamoeba histolytica (Eh), is the causative agent of amoebic dysentery and liver abscess in humans. It infects around 50 million people worldwide, which is a third general cause of death from parasitic diseases after malaria and schistosomiasis. The other prevalent form of the disease is Visceral leishmaniasis caused by Leishmania donovani which is a human blood parasite. On the other hand, the Toxoplasma gondii is an obligate intracellular protozoan parasite; it causes serious opportunistic infections in HIV‐positive persons. The biological processes in all living organisms are mostly mediated by the proteins, and recognizing new target proteins and finding their function in pathogenesis will help in choosing better diagnostic markers. In eukaryotes, Rab protein plays a major role in pathogenesis. Rabs represent the largest branch in the Ras superfamily of GTPases. Among them, the Rab5 is important in the endocytosis and thus involved in pathogenesis. In this paper, we discussed the physiochemical profiling, modelling, and docking of the Rab5 protein from pathogenic species that is Entamoeba histolytica, Leishmania donovani, and Toxoplasma gondii. The modeled structures from this study and the key residues identified would give a better understanding of the three‐dimensional structure and functional insights into these proteins and help in developing new drug targets.
Classifications in Brief: The Spinal Instability Neoplastic Score.

Identifying spinal instability plays a vital role in the management of patients with metastatic spinal disease. To appropriately triage and treat patients whowould benefit from surgical intervention, an accurate assessment of neoplastic spinal instability is imperative. Until recently, there was no consensus about how best to classify spinal instability in patients with neoplastic disease of the spine [14]. In the absence of robust evidence on this topic, knowledge about degenerative or traumatic instability has been applied to metastatic disease of the spine. However, such interpretations are problematic because pathologic fractures do not follow the usual patterns seen in patients with trauma and osteoporosis [5]. As opposed to traumatic conditions, ligaments and discs are less commonly affected by tumors, and the ability of the spine to heal is compromised [5]. Thus, classifications of spinal instability based on trauma may not be applicable to tumors. With a lack of guidelines, physicians have relied on clinical experience to determine whether instability is present in patients with spinal neoplasia [6]. For the nonsurgeon, difficulty diagnosing spinal instability can lead to inappropriate referrals of patients without instability or undertreatment of patients with instability. This highlights the need for a classification system to facilitate communication and to help identify which lesions are unstable and may benefit from evaluation by a spine surgeon. In 2010, the Spinal Oncology Study Group introduced the Spinal InstabilityNeoplastic score (SINS) to standardize the diagnosis of spinal instability in patients with neoplastic disease [6]. The Spinal Oncology StudyGroup, an international group of 30 spine oncology experts, developed the SINS using an evidence-based medicine process incorporating the best available studies and expert-opinion consensus.
Control of Translation at the Initiation Phase During Glucose Starvation in Yeast

Glucose is one of the most important sources of carbon across all life. Glucose starvation is a key stress relevant to all eukaryotic cells. Glucose starvation responses have important implications in diseases, such as diabetes and cancer. In yeast, glucose starvation causes rapid and dramatic effects on the synthesis of proteins (mRNA translation). Response to glucose deficiency targets the initiation phase of translation by different mechanisms and with diverse dynamics. Concomitantly, translationally repressed mRNAs and components of the protein synthesis machinery may enter a variety of cytoplasmic foci, which also form with variable kinetics and may store or degrade mRNA. Much progress has been made in understanding these processes in the last decade, including with the use of high-throughput/omics methods of RNA and RNA:protein detection. This review dissects the current knowledge of yeast reactions to glucose starvation systematized by the stage of translation initiation, with the focus on rapid responses. We provide parallels to mechanisms found in higher eukaryotes, such as metazoans, for the most critical responses, and point out major remaining gaps in knowledge and possible future directions of research on translational responses to glucose starvation.
Differential Actions of Estrogen Receptor α and β via Non-Genomic Signaling in Human Prostate Stem and Progenitor Cells.

Human prostate stem and progenitor cells express estrogen receptors (ERs) ERα and ERβ and exhibit proliferative responses to estrogens. Herein, membrane-initiated estrogen signaling was interrogated in human prostate stem-progenitor cells enriched from primary epithelial cultures and stem-like cell lines from benign and cancerous prostates. Subcellular fractionation and proximity ligation assays localized ERα and ERβ to the cell membrane with cavelolin-1 interactions. Exposure to 17β-estradiol (E2) for 15-60 min led to sequential phosphorylation of signaling molecules in MAPK and AKT pathways, IGF1R, EGFR and ERα, thus documenting an intact membrane signalosome that activates diverse downstream cascades. Treatment with an E2-dendrimer conjugate or ICI-182,870 validated E2-mediated actions through membrane ERs. Overexpression and knockdown of ERα or ERβ in stem-progenitor cells identified pathway selectivity; ERα preferentially activated AKT whereas ERβ selectively activated MAPK cascades. Further, prostate cancer stem-like cells expressed only ERβ and brief E2 exposure activated MAPK but not AKT cascades. A gene subset selectively regulated by nongenomic E2 signaling was identified in normal prostate progenitor cells that includes BGN, FOSB, FOXQ1 and MAF. Membrane-initiated E2 signaling rapidly modified histone methyl transferases with MLL1 cleavage observed downstream of p-AKT and EZH2 phosphorylation downstream of MAPK-signaling, which may jointly modify histones to permit rapid gene transcription. Together, the present findings document ERα and ERβ membrane-initiated signaling in normal and cancerous human prostate stem-progenitor cells with differential engagement of downstream effectors. These signaling pathways influence normal prostate stem-progenitor cell homeostasis and provide novel therapeutic sites to target the elusive prostate cancer stem cell population.
Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination. Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated. In the current study, we demonstrate that THC+CBD combination therapy (10 mg/kg each) but not THC or CBD alone, attenuates murine experimental autoimmune encephalomyelitis (EAE) by reducing neuroinflammation and suppression of Th17 and Th1 cells. These effects were mediated through CB1 and CB2 receptors inasmuch as, THC+CBD failed to ameliorate EAE in mice deficient in CB1 and CB2. THC+CBD treatment also caused a decrease in the levels of brain infiltrating CD4+ T cells and pro-inflammatory molecules (IL-17, INF-γ, TNF-α, IL-1β, IL-6, and TBX21), while increasing anti-inflammatory phenotype such as FoxP3, STAT5b, IL-4, IL-10, and TGF-β. Also, the brain-derived cells showed increased apoptosis along with decreased percentage in G0/G1 phase with increased percentage in G2/M phase of cell cycle. miRNA microarray analysis of brain-derived CD4+ T cells revealed that THC+CBD treatment significantly down-regulated miR-21a-5p, miR-31-5p, miR-122-5p, miR-146a-5p, miR-150-5p, miR-155-5p, and miR-27b-5p while upregulating miR-706-5p and miR-7116. Pathway analysis showed that majority of the down-regulated miRs targeted molecules involved in cycle arrest and apoptosis such as CDKN2A, BCL2L11, and CCNG1, as well as anti-inflammatory molecules such as SOCS1 and FoxP3. Additionally, transfection studies involving miR-21 and use of Mir21−/− mice suggested that while this miR plays a critical role in EAE, additional miRs may also be involved in THC+CBD-mediated attenuation of EAE. Collectively, this study suggests that combination of THC+CBD suppresses neuroinflammation and attenuates clinical EAE development and that this effect is associated with changes in miRNA profile in brain-infiltrating cells.
Assessing Satellite Image Data Fusion with Information Theory Metrics

A common problem in remote sensing is estimating an image with high spatial and high spectral resolution given separate sources of measurements from satellite instruments, one having each of these desirable properties. This thesis presents a survey of seven families of algorithms which have been developed to provide this common pattern of satellite image data fusion. They are all tested on artificially degraded sets of satellite data from the Moderate Resolution Imaging Spectroradiometer (“MODIS”) with known ideal results, and evaluated using the commonly accepted data fusion assessment metrics spectral angle mapper (“SAM”) and Erreur Relative Globale Adimensionelle de Synthèse (“ERGAS”). It is also established that the information theory metric mutual information can predict the performance of certain data fusion algorithms (pan-sharpening, principal component analysis (“PCA”) based, and high-pass filter (“HPF”) based) but not others.
Drosophotoxicology: Elucidating Kinetic and Dynamic Pathways of Methylmercury Toxicity in a Drosophila Model

The risks of methylmercury (MeHg) toxicity are greatest during early life where it has long been appreciated that the developing nervous system is an especially sensitive target. Yet, understanding the discrete mechanisms of MeHg toxicity have been obscured by the wide variation in the nature and severity of developmental outcomes that are typically seen across individuals in MeHg exposed populations. Some insight has come from studies aimed at identifying a role for genetic background as a modifier of MeHg toxicity, which have predominantly focused on factors influencing MeHg toxicokinetics, notably, polymorphisms in genes related to glutathione (GSH) metabolism. For example, variants in genes encoding the catalytic and modifier subunits of glutamyl-cysteine ligase (GCLc and GCLm), the rate limiting enzyme for GSH synthesis, have been reported to associate with Hg body burden (Hg levels in blood or hair) in humans. However, GSH can facilitate both toxicokinetics and toxicodynamics of MeHg by forming MeHg-GSH conjugates, which are readily transported and excreted, and by acting indirectly as an anti-oxidant. In this study, we refine a model to distinguish kinetic and dynamic traits of MeHg toxicity using a paradigm of Drosophotoxicolgy. First, we identify that the pupal stage is selectively sensitive to MeHg toxicity. Using a protocol of larval feeding, measurements of Hg body burden, and assays of development to adulthood (pupal eclosion), we identify strain-dependent variation in MeHg elimination as a potential kinetic determinant of differential tolerance to MeHg. We also find that global upregulation of GSH levels, with GCLc trans-gene expression, can induce MeHg tolerance and reduce Hg body burden. However, we demonstrate that MeHg tolerance can also be achieved independently of reducing Hg body burden, in both wild-derived strains and with targeted expression of GCLc in developing neuronal and muscle tissue, pointing to a robust toxicodynamic mechanism. Our findings have important implications for understanding variation in MeHg toxic potential on an individual basis and for informing the process of relating a measurement of Hg body burden to the potential for adverse developmental outcome.
Retracted: Amentoflavone Promotes Apoptosis in Non‐Small‐Cell Lung Cancer by Modulating Cancerous Inhibitor of PP2A

Non‐small‐cell lung cancer (NSCLC) is one of the most common human malignancies. Amentoflavone (AF) is one of bioflavonoid compounds isolated from Selaginella tamariscina Spring. This study was designed to examine the effect of AF on NSCLC. Our results indicated that AF decreased cell viability of both H1299 and H358 cells. Colony formation assay also showed that AF was able to suppress the anchorage‐independent growth of NSCLC cells. AF also triggered cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6. The pro‐apoptotic activity of AF was confirmed by Hoechst staining and flow cytometry. The effect of AF on activation of caspase‐3, upregulation of Bax, and downregulation of Bcl‐2 was examined by western blot. The anti‐growth and pro‐apoptotic activities of AF were further validated in xenograft murine model. iTRAQ assay showed that cancerous inhibitor of PP2A (CIP2A) expression was markedly downregulated by AF treatment in H1299 cells. In addition, qRT‐PCR and western blot also showed that AF was able to dose‐dependently inhibit CIP2A expression. Meanwhile, the activity of protein phosphatase 2A (PP2A) was enhanced by AF treatment. The mRNA and protein expression of CIP2A as well as PP2A activity in xenograft tumor tissue were examined, which indicated that the in vivo anticancer activity of AF was associated with downregulation of CIP2A and reactivation of PP2A. Moreover, our results showed that the anti‐growth and pro‐apoptotic activities of AF were augmented by CIP2A knockdown and attenuated by ectopic CIP2A expression. Our results indicated that AF exhibited anticancer activity in NSCLC by targeting CIP2A. Anat Rec, 302:2201–2210, 2019. © 2019 American Association for Anatomy
Next-Generation Sequencing Technologies for Early-Stage Cutaneous T-Cell Lymphoma

The diagnosis of early stage cutaneous T-cell lymphoma is often difficult, particularly in mycosis fungoides (MF), because the clinical presentation, histological findings, and laboratory findings of MF resemble those of inflammatory skin diseases such as atopic dermatitis, psoriasis, and parapsoriasis en plaque. Furthermore, MF sometimes occurs with or after these inflammatory skin diseases. The current diagnostic criteria heavily rely on clinical impressions along with assessments of T cell clonality. To make a diagnosis of early-stage MF, the detection of a malignant clone is critical. T cell receptor (TCR) gene rearrangements have been detected by southern blotting or polymerase chain reaction for this purpose, but the results of these methods are insufficient. High-throughput TCR sequencing has provided insights into the complexities of the immune repertoire. Accordingly, his technique is more sensitive and specific than current methods, making it useful for the detection of early lesions and monitoring responses to therapy.
Bone formation activity of an osteogenic dodecapeptide from blue mussels (Mytilus edulis).

A novel osteogenic dodecapeptide peptide (PIE), IEELEEELEAER, was purified from the protein hydrolysate of blue mussels (Mytilus edulis). PIE was identified using a capillary electrophoresis electrospray ionization-quadrupole-time of flight mass spectrometer. PIE showed a good reduction in the bone loss in ovariectomized mice, and it also increased the bone mineral density of the ovariectomized mice. PIE has a high affinity with integrins (PDB: 1L5G, 3VI4). There are 8 and 12 amino acid residues from PIE that interact with integrins 1L5G and 3VI4, respectively. PIE accelerates the transformation of G0/G1 phase cells into G2 M phase cells, which promotes the growth of osteoblasts. PIE (100 μg mL-1) can enhance alkaline phosphatase (ALP) activity by 26.48% compared with the control, and it also inhibits the growth of osteoclasts and tartrate resistant acid phosphatase (TRAP) activity. Therefore, PIE may contribute to preventing osteoporosis both in vitro and in vivo.
Reverse signaling by semaphorin 4C elicits SMAD1/5- and ID1/3-dependent invasive reprogramming in cancer cells

As a receptor, semaphorin 4C hijacks TGF-β signaling to promote metastatic breast cancer growth. Semaphorins in reverse Members of the large family of semaphorins guide cell migration. As ligands, some semaphorins are implicated in promoting cancer progression and angiogenesis. Gurrapu et al. found an alternative mechanism in which semaphorin 4C (Sema4C) acts as a receptor to promote metastasis. In response to interaction with the extracellular domain of PlexinB2 (which is a receptor when Sema4C acts as a ligand), transmembrane-resident Sema4C intracellularly interacted with and activated TGF-β receptors in invasive breast cancer cell lines. Subsequent changes in gene expression suppressed mesenchymal features and promoted metastasis in a mouse model of disseminated-cell seeding and growth. These findings reveal one way in which Sema4C promotes the cellular plasticity necessary for metastatic disease. Semaphorins are a family of molecular signals that guide cell migration and are implicated in the regulation of cancer cells. In particular, transmembrane semaphorins are postulated to act as both ligands (“forward” mode) and signaling receptors (“reverse” mode); however, reverse semaphorin signaling in cancer is relatively less understood. Here, we identified a previously unknown function of transmembrane semaphorin 4C (Sema4C), acting in reverse mode, to elicit nonconventional TGF-β/BMP receptor activation and selective SMAD1/5 phosphorylation. Sema4C coimmunoprecipitated with TGFBRII and BMPR1, supporting its role as modifier of this pathway. Sema4C reverse signaling led to the increased abundance of ID1/3 transcriptional factors and to extensive reprogramming of gene expression, which suppressed the typical features of the epithelial-mesenchymal transition in invasive carcinoma cells. This phenotype was nevertheless coupled with burgeoning metastatic behavior in vivo, consistent with evidence that Sema4C expression correlates with metastatic progression in human breast cancers. Thus, Sema4C reverse signaling promoted SMAD1/5- and ID1/3-dependent gene expression reprogramming and phenotypic plasticity in invasive cancer cells.