Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilization of Reactive Oxygen Species Targeted Therapy to Prolong the Efficacy of BRAF Inhibitors in Melanoma

BRAF mutations occur in about 50% of melanoma patients. FDA approved BRAF and MEK inhibitors have improved the prognosis of patients with BRAF mutations. However, all responders develop resistance typically within one year of treatment. Recent observations demonstrate that BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells. A100, identified from a library screen, is a ROS-activated prodrug that self-cyclizes into a stable bicyclic ring and causes DNA double strand breaks. We proposed to examine if ROS activated therapy will inhibit tumor growth and evade resistance to BRAF inhibitors. In this study, the BRAF inhibitor dabrafenib was used to generate resistant cell lines (A375DR, SK-MEL-24DR and WM-115DR). Flow cytometry experiments showed that ROS levels are increased in these dabrafenib-resistant cells as compared to parental cells, assessed by both the H2DCFDA and MitoSOX assays. Furthermore, we observed that resistant cells had increased levels of the mitochondrial enzymes SOD2 and PRDX1, which function to reduce ROS levels in the mitochondria. We found that A100 sensitized the resistant melanoma cells to dabrafenib and induced DNA damage. Co-treatment of both A100 and dabrafenib significantly suppressed in vitro cell proliferation and three- dimensional (3D) matrigel growth. This study suggests that the combination of A100 with a BRAF inhibitor could be a potential strategy to treat melanoma patients with BRAF mutations.
Corynebacterium pseudotuberculosis mastitis in Egyptian dairy goats

Background and Aim Mastitis is an important threat facing goat milk industry and is the most common cause of culling. Efficient control of mastitis, based on efficient diagnosis of diseased animals, would improve milk production and reproductive efficiency. In subclinical mastitis (SCM), infected goats demonstrate neither udder symptoms nor abnormal milk. Corynebacterium pseudotuberculosis is an infectious causative agent of mastitis, mostly results as an extension of infection from the supramammary lymph node, and causes financial losses in the goat industry. This study aimed to estimate the prevalence of SCM with emphasis on C. pseudotuberculosis mastitis in Egyptian dairy goats in the selected farms. Materials and Methods A total of 336 half milk samples were collected from 177 dairy goats of various crossbreeds, in mid-to-late lactation period, after clinical examination. All samples were examined bacteriologically, while somatic cell count (SCC) was determined only in 180 half milk samples of the clinically healthy milk samples. The isolated and identified C. pseudotuberculosis was examined for evidence of virulence genes (Phospholipase D [pld] and β-subunit of RNA polymerase [rpoB]) by polymerase chain reaction (PCR). Results The prevalence of clinical mastitis was 30.5%, while 69.5% of animals were apparently healthy and secreted milk was normal. Of those 180 clinically healthy half milk samples, 96 milk samples (53.33%) showed SCM as detected by SCC (SCC ≥1,000,000 cells/ml). Coagulase-negative staphylococci were the most prevalent bacteria (41.96%), then Staphylococcus aureus (37.5%) and C. pseudotuberculosis (7.14%). Molecular diagnosis of virulence genes revealed evidence of pld gene in 16 isolates (66.66%), and rpoB gene in 6 samples (25%) of the 24 bacteriologically isolated C. pseudotuberculosis. Here, we describe, for the 1st time, isolation and identification of C. pseudotuberculosis from milk of does suffering from SCM in Egypt. Conclusion C. pseudotuberculosis must be considered for routine bacteriological examination of milk from dairy goats, particularly herds with a history of caseous lymphadenitis. Pld gene-based PCR is more reliable than rpoB gene-based ones for the diagnosis of C. pseudotuberculosis.
Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles

Introduction Magnetic drug targeting utilizes superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate drugs in specified vasculature regions. Methods We produced SPIONs conjugated with dexamethasone phosphate (SPION-DEXA). The efficacy of magnetic drug targeting was investigated in a rabbit model of atherosclerosis induced by balloon injury and high cholesterol diet. Results In vitro, SPION-DEXA were well-tolerated by endothelial cells. SPION-DEXA were internalized by human peripheral blood mononuclear cells and induced CD163 expression comparable with the free drug. In vivo, magnetic targeting of SPIONs to abdominal aorta was confirmed by histology. Upon vascular injury followed by high-cholesterol diet, early administration of SPION-DEXA enhanced the inflammatory burden in the plaques. Increased macrophage content and larger intima– media thickness were observed in animals treated with SPION-DEXA compared with controls. In advanced atherosclerosis, no beneficial effect of local glucocorticoid therapy was detectable. Conclusion Magnetic drug targeting represents an efficient platform to deliver drugs to diseased arteries in vivo. However, targeting of vascular injury in the lipid-rich environment using dexamethasone-conjugated SPIONs may cause accelerated inflammatory response.
Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy

Objective To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. Methods Patients with presumed LGMD and unrevealing genetic testing were selected based on a few clinico-pathologic features and tested for anti-HMGCR autoantibodies (n = 11). These clinico-pathologic features are peak creatine kinase (CK) greater than 1,000 IU/L and at least 3 of the following features: (1) limb-girdle pattern of weakness, (2) selective involvement of posterior thigh on clinical examination or muscle imaging, (3) dystrophic changes on muscle biopsy, and (4) no family history of muscular dystrophy. Results Six patients tested positive for anti-HMGCR autoantibodies. In 4, there was a presymptomatic phase, lasting as long as 10 years, characterized by elevated CK levels without weakness. Muscle biopsies revealed variable degrees of a dystrophic pathology without prominent inflammation. In an independent cohort of patients with anti-HMGCR myopathy, 17 of 51 (∼33%) patients were initially presumed to have a form of LGMD based on clinico-pathologic features but were ultimately found to have anti-HMGCR myopathy. Most of these patients responded favorably to immunomodulatory therapies, evidenced by reduction of CK levels and improved strength. Conclusions Anti-HMGCR myopathy can resemble LGMD. Diagnosis of patients with a LGMD-like presentation of anti-HMGCR myopathy is critical because these patients may respond favorably to immunotherapy, especially those with shorter disease duration.
Timing of neovascular regression in eyes with high-risk proliferative diabetic retinopathy without macular edema treated initially with intravitreous bevacizumab

Purpose To determine the timing of neovascular regression after intravitreous injection of bevacizumab (Avastin®) 1.25 mg given as initial therapy for eyes with high-risk proliferative diabetic retinopathy (PDR) without clinically significant macular edema (CSME). Patients and methods In this prospective uncontrolled interventional study, eyes with high-risk PDR without CSME were treated initially with intravitreous injections of bevacizumab 1.25 mg given every 4 weeks until no neovessels were detected, followed by standard pan-retinal photocoagulation (PRP). Patients were examined 48 hours, 1, 2, and 4 weeks after each injection to determine the status of neovascularization. Results Twenty-one patients (24 eyes) were included in the study. Forty-eight hours after the first injection of bevacizumab, we observed complete neovascular regression in 20 (83%) eyes. Neovascular regression was maintained in the same number of eyes in the first 2 weeks. At 4 weeks, three eyes displayed neovascular recurrence, and a second injection of bevacizumab was given to the seven eyes with persistent or recurrent neovascularization. Complete neovascular regression was observed in six (86%) eyes after 48 hours and was maintained for 2 weeks following the second bevacizumab injection. Two eyes required a third injection and had complete neovascular regression when assessed after 48 hours and 4 weeks. Conclusion The majority of neovessels completely regressed within 48 hours after intra-vitreous injection of bevacizumab given as initial therapy for high-risk PDR without CSME. The full neovascular regressive effect occurred within 48 hours and was maintained for at least 2 weeks.
Physical activity increases the resistin concentration in hemodialyzed patients without metabolic syndrome

Background Resistin (RES) concentration increases in end-stage renal disease patients. However, there have been no studies defining the role of physical activity in RES concentrations in hemodialyzed (HD) patients. This study was aimed to determine metabolic and inflammatory effects, including RES, of 4-week supervised rehabilitation program in HD patients, with or without metabolic syndrome (MS). Methods The study was completed by 28 patients aged 56.9±13.3 years (x¯±SD) who were HD for 50.6±73.4 months, and 30 controls aged 61.5±8.3 years with normal renal function. Both the groups were divided into two subgroups with respect to MS. Individualized supervised rehabilitation program based on physiotherapy, including exercises, was provided to each subject for 4 weeks. Baseline and post-intervention complete blood count, glycated hemoglobin (HbA1c) and levels of serum RES, leptin, adiponectin, cystatin C, erythropoietin, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6, transforming growth factor- β1, plasminogen activator inhibitor-1 homocysteine, insulin, albumin, parathyroid hormone (PTH), and phosphorus were measured. Results Compared to controls, HD patients showed higher baseline leucocytes count and higher serum concentrations of RES, leptin, cystatin C, hs-CRP, TNF-α, homocysteine, phosphorus, PTH while hemoglobin, glucose, and albumin concentrations. A positive correlation between serum albumin and RES concentrations was observed in HD patients. Post-intervention RES increase was observed in HD patients without MS (post-intervention 34.22±8.89 vs baseline 30.16±11.04 ng/mL; P=0.046) while no change was observed in patients with MS and in the control group. Conclusion MS modifies a RES response to the rehabilitation program in HD patients.
miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting ZEB1

Background miRNAs have been found to be dysregulated in cervical cancer. The dysregulation of miRNA has been implicated in cervical carcinogenesis and progression. Therefore, further studies of the specific roles of deregulated miRNAs in cervical cancer and underlying molecular mechanisms may facilitate the identification of novel therapeutic techniques for patients with this disease. miRNA-641 (miR-641) was previously reported to serve an important role in lung cancer. However, the expression pattern and roles of miR-641 in cervical cancer remain unclear. Method In this study, the expression level of miR-641 in cervical cancer tissues and cell lines was detected using RT-qPCR. The influence of miR-641 upregulation in cervical cancer cell proliferation, apoptosis, migration and invasion was evaluated using CCK-8 assay, flow cytometry assay, migration and invasion assays, respectively. In vivo tumor growth assay was utilized to determine the effect of miR-641 overexpression in the tumor growth of cervical cancer cells in vivo. The molecular mechanisms underlying the action of miR-641 in cervical cancer cells were also explored. Results We found that miR-641 expression was obviously decreased in cervical cancer tissues and cell lines, which strongly correlated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Upregulation of miR-641 inhibited cell proliferation, induced apoptosis, and reduced metastasis in cervical cancer. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-641. Notably, luciferase reporter assay, RT-qPCR, and Western blot analysis revealed that miR-641 decreased ZEB1 expression in cervical cancer cells by directly targeting its 3′-untranslated region. Furthermore, ZEB1 was upregulated in cervical cancer tissues, which was negatively correlated with miR-641 expression. Moreover, recovered ZEB1 expression attenuated the tumor suppressive action of miR-641 overexpression in the malignant phenotypes of cervical cancer cells. Besides, miR-641 could hinder cervical cancer tumor growth in vivo by inhibiting ZEB1. Conclusion These results indicate that miR-641 has tumor suppressive roles in the development of cervical cancer by directly targeting ZEB1, suggesting that miR-641 is a novel, effective therapeutic target for treating patients with this disease.
“We feel included”: education and inclusion of health care staff with minority language in elder care

Background In Norwegian elder care, an increasing percentage of the health care staff has a migrant background. “The aging and nursing care ABC” educational program offers multi-component training for municipal care staff to systematically improve their competence in elder care. The program consists of written material organized into booklets, regular multidisciplinary reflection group meetings, and a full-day workshop in each semester. In 2017, a Norwegian municipality included migrant health care personnel in an educational Minority ABC-model (Min. ABC), systematically focusing on processes relevant for interaction between majority and minority health care staff. Aim To investigate the experiences of the participants in the Min. ABC-model, focusing on the processes and relationships between native participants with Norwegian language and migrants with other lingual backgrounds. Method The study has a qualitative design, and draws on four focus group interviews, one group interview, and four individual interviews with a total of 23 female Min. ABC-model participants. Data were analyzed using an approach outlined by Corbin and Strauss. Results Our analysis resulted in six main themes: 1) reaching equality, 2) sharing experiences, 3) communication and language, 4) relations to the elderly, 5) differences and discrimination, and 6) lessons learnt. Conclusion Our findings indicate that the Min. ABC-model of the ABC program contributes to better the competence and interaction among personnel with migrant and native lingual backgrounds. The participants describe increased inclusion at work, as well as integration into a more holistic form of teamwork in elder care.
Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

Introduction and objective Currently, carbon nanostructures are vastly explored materials with potential for future employment in biomedicine. The possibility of employment of diamond nanoparticles (DN), graphene oxide (GO) or graphite nanoparticles (GN) for in vivo applications raises a question of their safety. Even though they do not induce a direct toxic effect, due to their unique properties, they can still interact with molecular pathways. The objective of this study was to assess if DN, GO and GN affect three isoforms of cytochrome P450 (CYP) enzymes, namely, CYP1A2, CYP2D6 and CYP3A4, expressed in the liver. Methods Dose-dependent effect of the DN, GO and GN nanostructures on the catalytic activity of CYPs was examined using microsome-based model. Cytotoxicity of DN, GO and GN, as well as the influence of the nanostructures on mRNA expression of CYP genes and CYP-associated receptor genes were studied in vitro using HepG2 and HepaRG cell lines. Results All three nanostructures interacted with the CYP enzymes and inhibited their catalytic activity in microsomal-based models. CYP gene expression at the mRNA level was also downregulated in HepG2 and HepaRG cell lines. Among the three nanostructures, GO showed the most significant influence on the enzymes, while DN was the most inert. Conclusion Our findings revealed that DN, GO and GN might interfere with xenobiotic and drug metabolism in the liver by interactions with CYP isoenzymes responsible for the process. Such results should be considered if DN, GO and GN are used in medical applications.
The construction and analysis of ceRNA networks in invasive breast cancer: a study based on The Cancer Genome Atlas

Background Studies have shown that long noncoding RNAs (lncRNAs) make up the major proportion of the ceRNA network and can regulate gene expression by competitively binding to miRNAs. This reveals the existence of an RNA-miRNA regulatory pathway and is of great biological significance. CeRNAs, as competitive endogenous RNAs, have revealed a new mechanism of interaction between RNAs. Until now, the role of lncRNA-mediated ceRNAs in breast cancer and their regulatory mechanisms have been elucidated to some extent. Purpose In this study, comprehensive analysis of large-scale invasive breast cancer samples in TCGA were conducted to further explore the developmental mechanism of invasive breast cancer and the potential predictive markers for invasive breast cancer prognosis in the ceRNA network. Methods Abnormal expression profiles of invasive breast cancer associated mRNAs, lncRNAs and miRNAs were obtained from the TCGA database. Through further alignment and prediction of target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network was constructed for invasive breast cancer. Through the overall survival analysis, Identification prognostic bio-markers for invasive breast cancer patients. In addition, we used Cytoscape plug-in BinGo for the different mRNA performance functional cluster analysis. Results Differential analysis revealed that 1059 lncRNAs, 86 miRNAs, and 2138 mRNAs were significantly different in invasive breast cancer samples versus normal samples. Then we construct an abnormal lncRNA-miRNA-mRNA ceRNA network for invasive breast cancer, consisting of 90 DElncRNAs, 18 DEmiRNAs and 26 DEmRNAs.Further, 4 out of 90 lncRNAs, 3 out of 26 mRNAs, and 2 out of 18 miRNAs were useful as prognostic biomarkers for invasive breast cancer patients (P value < 0.05). It is worth noting that based on the ceRNA network, we found that the LINC00466-Hsa-mir-204- NTRK2 LINC00466-hsa-mir-204-NTRK2 axis was present in 9 RNAs associated with the prognosis of invasive breast cancer. Conclusion This study provides an effective bioinformatics basis for further understanding of the molecular mechanism of invasive breast cancerand for predicting outcomes, which can guide the use of invasive breast cancerdrugs and subsequent related research.
Biogenic Volatile Compounds for Plant Disease Diagnosis and Health Improvement

Plants and microorganisms (microbes) use information from chemicals such as volatile compounds to understand their environments. Proficiency in sensing and responding to these infochemicals increases an organism's ecological competence and ability to survive in competitive environments, particularly with regard to plant-pathogen interactions. Plants and microbes acquired the ability to sense and respond to biogenic volatiles during their evolutionary history. However, these signals can only be interpreted by humans through the use of state-of the-art technologies. Newly-developed tools allow microbe-induced plant volatiles to be detected in a rapid, precise, and non-invasive manner to diagnose plant diseases. Beside disease diagnosis, volatile compounds may also be valuable in improving crop productivity in sustainable agriculture. Bacterial volatile compounds (BVCs) have potential for use as a novel plant growth stimulant or as improver of fertilizer efficiency. BVCs can also elicit plant innate immunity against insect pests and microbial pathogens. Research is needed to expand our knowledge of BVCs and to produce BVC-based formulations that can be used practically in the field. Formulation possibilities include encapsulation and sol-gel matrices, which can be used in attract and kill formulations, chemigation, and seed priming. Exploitation of biogenic volatiles will facilitate the development of smart integrated plant management systems for disease control and productivity improvement.
Elevated Tumor Necrosis Factor-a-induced Protein 8-like 2 mRNA from Peripheral Blood Mononuclear Cells in Patients with Acute Ischemic Stroke

Background: Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel regulator of immunity and protects against experimental stroke. However, the expression and function of TIPE2 in patients with acute ischemic stroke has not been well demonstrated. Methods: A total of 182 consecutive patients with acute ischemic stroke and 40 healthy controls were included during November 2015 to June 2016. The mRNA levels of TIPE2, interleukin(IL)-1β, IL-10, IL-6, nuclear factor(NF)-κβ, activator protein(AP)-1, interferon(IFN)-γ and tumor necrosis factor(TNF)-α from peripheral blood mononuclear cells were determined using real time quantitative reverse transcriptase polymerase chain reaction. The severity of stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. Results: The median mRNA levels of TIPE2, TNF-α, AP-1, IFN-γ and NF-κβ in patients with acute ischemic stroke were significantly higher than healthy controls (all P<0.001, respectively). Of note, TIPE2 mRNA showed an increasing trend on a time-dependent manner after the onset of stroke. Furthermore, TIPE2 mRNA was negatively associated with lesion volumes (r=-0.23, P<0.01), NIHSS(r=-0.15, P<0.05), TNF-α(r=-0.33,P<0.001), AP-1(r=-0.28,P<0.001), IFN-γ (r=-0.16, P<0.05) and NF-κβ (r=-0.13, P<0.05), but positively associated with IL-6(r=0.14, P<0.05) and IL-10(r=-0.31, P<0.001). Hierarchy cluster analysis showed that TIPE2 mRNA has nearest membership with TNF-α, followed by IL-6, NF-κβ, AP-1, IL-10, IL-1β and IFN-γ. In addition, TIPE2 mRNA in survivals (n=149) was significantly higher than nonsurvivals (n=33) (P<0.001), and showed a great odd ratio (0.52, 95% confidence interval: 0.349-0.760, P<0.001) on 3-month mortality. Conclusions: TIPE2 mRNA contributed to the immune response of stroke and might be a potential biomarker for the mortality of acute ischemic stroke.