Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Although oxidative stress has been long associated with the genesis and progression of the atherosclerotic plaque, scanty data on its in situ effects on protein sulfhydryl group modifications are available. Within the arterial wall, protein sulfhydryls and low-molecular-weight (LMW) thiols are involved in the cell regulation of both Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) levels and are a target for several posttranslational oxidative modifications that take place inside the atherosclerotic plaque, probably contributing to both atherogenesis and atherosclerotic plaque progression towards complicated lesions. Advanced carotid plaques are characterized by very high intraplaque GSH levels, due to cell lysis during apoptotic and/or necrotic events, probably responsible for the altered equilibrium among protein sulfhydryls and LMW thiols. Some lines of evidence show that the prooxidant environment present in atherosclerotic tissue could modify filtered proteins also by protein-SH group oxidation, and demonstrate that particularly albumin, once filtered, represents a harmful source of homocysteine and cysteinylglycine inside the plaque. The oxidative modification of protein sulfhydryls, with particular emphasis to protein thiolation by LMW thiols and its association with atherosclerosis, is the main topic of this review.
MicroRNA-384 Inhibits the Progression of Papillary Thyroid Cancer by Targeting PRKACB

Background Growing evidence shows that dysregulation of miRNAs plays a significant role in papillary thyroid cancer (PTC) tumorigenesis and development. The abnormal expression of miR-384 has been acknowledged in the proliferation or metastasis of some cancers. However, the function and the underlying mechanism of miR-384 in PTC progression remain largely unknown. Methods Real-time PCR was conducted to detect miR-384 expression in 58 cases of PTC and their adjacent noncancerous tissues. MTT, soft agar assay Transwell assay, and wound-healing assay were carried out to explore the biological function of miR-384 in PTC cell lines of BCPAP and K1. Bioinformatics analysis, dual-luciferase reporter assay, western blot, and functional complementation analysis were conducted to explore the target gene of miR-384. Moreover, Spearman's correlation analysis was conducted to reveal the correlation between miR-384 and PRKACB mRNA in PTC. Results The expression of miR-384 decreased obviously in PTC, especially in the tumors with lymph node metastasis or larger tumor size. The ectopic upregulation of miR-384 significantly suppressed PTC progression, and the inhibition of miR-384 had the opposite effects. Moreover, PRKACB gene was confirmed as the target of miR-384. Conclusion The study suggests that miR-384 serves as a tumor suppressor in PTC progression by directly targeting the 3′-UTR of PRKACB gene.
A computational approach to the study of interactions between proteins and miR10-b, miR-335, and miR-21 involved in breast cancer

MiR-10b, miR-335, and miR-21 are classes of microRNAs (miRNAs) that are overexpressed in breast cancer. Thus, in our study we aimed to test the hypothesis that miRNAs may have direct interactions with proteins and the possibility to inhibit/activate the functional site of proteins and enzymes. For this purpose, we choose three miRNAs involved in breast cancer to study interactions between some proteins and genes, including BRCA1 and PTEN, by processing the docking and matching tools using the Hex8 and HADDOCK server. Mathematically, the hidden Markov models were created by using MATLAB script according to the algorithm in order to study and validate the interactions and bonds between proteins and miRNAs. The main results demonstrate the ability of miR-10b, miR-335, and miR-21 to create direct interactions with 3D protein structures. Furthermore, these results may lead to another pathway of research, i.e. the direct interaction between proteins and their sub-units, to highlight the data obtained previously and demonstrate that proteins may directly interact with ncRNA instead of mRNA. Moreover, our study suggests developing research on different pathways of association proteins-miRNAs as a part of epigenetic extra-nuclear regulation. Taken together, our study provides the first evidence of direct interactions between miRNAs and proteins.
A 5-Gene Signature Is Closely Related to Tumor Immune Microenvironment and Predicts the Prognosis of Patients with Non-Small Cell Lung Cancer

Purpose Establishing prognostic gene signature to predict clinical outcomes and guide individualized adjuvant therapy is necessary. Here, we aim to establish the prognostic efficacy of a gene signature that is closely related to tumor immune microenvironment (TIME). Methods and Results There are 13,035 gene expression profiles from 130 tumor samples of the non-small cell lung cancer (NSCLC) in the data set GSE103584. A 5-gene signature was identified by using univariate survival analysis and Least Absolute Shrinkage and Selection Operator (LASSO) to build risk models. Then, we used the CIBERSORT method to quantify the relative levels of different immune cell types in complex gene expression mixtures. It was found that the ratio of dendritic cells (DCs) activated and mast cells (MCs) resting in the low-risk group was higher than that in the high-risk group, and the difference was statistically significant (P < 0.001 and P=0.03). Pathway enrichment results which were obtained by performing Gene Set Variation Analysis (GSVA) showed that the high-risk group identified by the 5-gene signature had metastatic-related gene expression, resulting in lower survival rates. Kaplan–Meier survival results showed that patients of the high-risk group had shorter disease-free survival (DFS) and overall survival (OS) than those of the low-risk group in the training set (P=0.0012 and P < 0.001). The sensitivity and specificity of the gene signature were better and more sensitive to prognosis than TNM (tumor/lymph node/metastasis) staging, in spite of being not statistically significant (P=0.154). Furthermore, Kaplan–Meier survival showed that patients of the high-risk group had shorter OS and PFS than those of the low-risk group (P=0.0035, P < 0.001, and P < 0.001) in the validating set (GSE31210, GSE41271, and TCGA). At last, univariate and multivariate Cox proportional hazard regression analyses were used to evaluate independent prognostic factors associated with survival, and the gene signature, lymphovascular invasion, pleural invasion, chemotherapy, and radiation were employed as covariates. The 5-gene signature was identified as an independent predictor of patient survival in the presence of clinical parameters in univariate and multivariate analyses (P < 0.001) (hazard ratio (HR): 3.93, 95% confidence interval CI (2.17–7.1), P=0.001, (HR) 5.18, 95% CI (2.6995–9.945), P < 0.001), respectively. Our 5-gene signature was also related to EGFR mutations (P=0.0111), and EGFR mutations were mainly enriched in low-risk group, indicating that EGFR mutations affect the survival rate of patients. Conclusion The 5-gene signature is a powerful and independent predictor that could predict the prognosis of NSCLC patients. In addition, our gene signature is correlated with TIME parameters, such as DCs activated and MCs resting. Our findings suggest that the 5-gene signature closely related to TIME could predict the prognosis of NSCLC patients and provide some reference for immunotherapy.
The Multifarious Link between Cytochrome P450s and Cancer

Cancer is a leading cause of death worldwide. Cytochrome P450s (P450s) play an important role in the metabolism of endogenous as well as exogenous substances, especially drugs. Moreover, many P450s can serve as targets for disease therapy. Increasing reports of epidemiological, diagnostic, and clinical research indicate that P450s are enzymes that play a major part in the formation of cancer, prevention, and metastasis. The purposes of this review are to shed light on the current state of knowledge about the cancer molecular mechanism involving P450s and to summarize the link between the cancer effects and the participation of P450s.
Health-related quality of life of hemophilics and its possible correlates: A perspective in health promotion and disability prevention

BACKGROUND: Clinical evaluations are not sufficient to adequately characterize the morbidity associated with hemophilia. Quality of life (QoL) of hemophilics and associated factors is not well explored in Indian research. The present study aimed to measure the QoL in hemophilics and its association with socio-demographic characteristics and other characteristics. MATERIALS AND METHODS: A cross-sectional study was conducted during June–November 2018. Two hundred and one hemophilics (age ≥ 4 years) were interviewed with a pre-tested schedule for sociodemographic and other relevant variables. QoL was measured by Haemo-QoL questionnaire for different pediatric age groups and Haem-A-QoL questionnaire for adults and assigned health-related QoL scores. Score achieved in each dimension as well as total scores were transformed on scales ranging from 0 to 100, high values indicate high impairment of QoL. Hemophilic arthropathy was assessed using the World Federation of Hemophilia Joint Scores. One-way ANOVA, independent t-test, Kruskal–Wallis test, and Spearman correlation analyses were performed using SPSS version 16. RESULTS: Mean Haemo-QoL scores for 4–7 years, 8–12 years, 13–16 years, and >16 years were 43.92 ± 8.09, 37.37 ± 8.62, 32.79 ± 6.66, and 45.92 ± 6.30, respectively. Significant difference was noted for QoL scores across different age groups, grades of severity, educational, occupational categories, socioeconomic status classes, marital status, and presence or absence of target joint. Total QoL scores, as well as scores in some of the dimensions, showed a significant positive correlation with the World Federation of Hemophilia joint scores by Spearman correlation analysis. CONCLUSIONS: Improvement of the joint health status by regular physiotherapy is needed to improve the QoL of hemophilics.
A review of the contribution of cowpea leaves to food and nutrition security in East Africa

Abstract Cowpea leaf is among the African indigenous vegetables that have been recommended for possible alleviation of food and nutrition insecurity in sub‐Saharan Africa (SSA). The vegetable is rich in micronutrients including iron and vitamin A whose deficiencies are prevalent in SSA. Considering the limitation of seasonal availability, preservation techniques have been adopted to enhance availability with little success. This review aims at highlighting the contribution of cowpeas leaves to food and nutrition security as well as research gaps that must be addressed to promote the utilization of value‐added forms that would have extended effect of improving its production and consumption. It was found that preserved and fresh cowpea leaves were rich in beta‐carotene and iron in the ranges of 0.25–36.55 and 0.17–75.00 mg/100 g dry weight, respectively. The proportion of rural households incorporating the vegetable in its various forms in the region can be as high as 30%. With adequate utilization, the vegetable provided up to ≥ 75% and 25% of RDAs for vitamin A and iron, respectively, of children aged 4–8. However, the utilization of preserved forms faced a limitation for a deviation of up to 30% in their sensory scores and decreased nutrient content as compared to the fresh ones hugely hindered their market penetration. Utilization of novel processing techniques incorporating concept of hurdle technology can help address these quality losses. In conclusion, preservation of cowpea leaves should seek not only to enhance the shelf‐life, but also to enhance acceptability of the products with a view of increased utilization.
Electroacupuncture Promoting Axonal Regeneration in Spinal Cord Injury Rats via Suppression of Nogo/NgR and Rho/ROCK Signaling Pathway

Purpose To observe the changes of Nogo/NgR and Rho/ROCK signaling pathway-related gene and protein expression in rats with spinal cord injury (SCI) treated with electroacupuncture (EA) and to further investigate the possible mechanism of EA for treating SCI. Methods Allen’s method was used to create the SCI rat model. Sixty-four model rats were further subdivided into four subgroups, namely, the SCI model group (SCI), EA treatment group (EA), blocking agent Y27632 treatment group (Y27632) and EA+blocking agent Y27632 treatment group (EA+Y), according to the treatment received. The rats were subjected to EA and/or blocking agent Y27632 treatment. After 14 days, injured spinal cord tissue was extracted for analysis. The mRNA and protein expression levels were determined by real-time fluorescence quantitative PCR and Western blotting, respectively. Cell apoptosis changes in the spinal cord were evaluated by in situ hybridization. Hindlimb motor function in the rats was evaluated by Basso-Beattie-Bresnahan assessment methods. Results Except for RhoA protein expression, compared with the SCI model group, EA, blocking agent Y27632 and EA+blocking agent Y27632 treatment groups had significantly reduced mRNA and protein expression of Nogo-A, NgR, LINGO-1, RhoA and ROCK II in spinal cord tissues, increased mRNA and protein expression of MLCP, decreased p-MYPT1 protein expression and p-MYPT1/MYPT1 ratio, and caspase3 expression, and improved lower limb movement function after treatment for 14 days (P<0.01 or <0.05). The combination of EA and the blocking agent Y27632 was superior to EA or blocking agent Y27632 treatment alone (P < 0.01 or <0.05). Conclusion EA may have an obvious inhibitory effect on the Nogo/NgR and Rho/ROCK signaling pathway after SCI, thereby reducing the inhibition of axonal growth, which may be a key mechanism of EA treatment for SCI.
The Possible Link Between Vitamin D Levels and Exudative Age-related Macular Degeneration

Objectives We sought to evaluate the possible correlation between serum vitamin D levels and exudative age-related macular degeneration (AMD). Methods We conducted a cross-sectional study including 95 patients with exudative AMD and 95 healthy age- and sex-matched controls. The participants’ serum 25-hydroxyvitamin D3 (25(OH)D3) levels were measured, and the results were classified into three categories: deficient (< 20.0 ng/mL), insufficient (20.1–29.9 ng/mL), and sufficient (>30.0 ng/mL). We compared serum 25(OH)D3 levels between the two study groups and the AMD ratio between the patients with deficient serum 25(OH)D3 levels and those with levels in the sufficient and insufficient ranges. Results The median 25(OH)D3 levels were significantly lower in patients with AMD compared to the control subjects (p = 0.042). The frequencies of patients with AMD among the vitamin D categories were statistically significant (p = 0.043). Subgroup analysis showed that the frequency of patients with AMD and deficient vitamin D levels was significantly higher than that found in the patients who had sufficient and/or insufficient ranges of vitamin D levels (55.0% vs. 36.0%, p = 0.043, respectively). Conclusions Serum 25(OH)D3 levels may have an impact on the neovascular type of AMD. As 25(OH)D3 levels decrease, the frequency of AMD increases.
Lifestyle and Sociodemographic and Economic Characteristics of Patients with Lung Cancer in Morocco

Background Lifestyle maintenance is a crucial condition before and after lung cancer disease. According to the previous research in the scientific databases, the effect of the interaction between socioeconomic and demographic factors on the lifestyle of lung cancer patients in Southern Morocco regions remains unexamined. Accordingly, this study was designed to examine the relationship between socioeconomic factors, demographic factors, and the lifestyle of lung cancer patients. Methods A total of 133 patients with lung cancer were divided into 103 men and 30 women with a sex ratio of 3.43 and ages varying between 28 and 82 years, and they served as informants for the study and filled in a questionnaire to provide information on their sociodemographic background, various economic characteristics, and their lifestyle. These patients have also been submitted to an anthropometric examination following the standardized procedure recommended by the World Health Organization. The survey was conducted from July 2013 to March 2015 at the Oncology and Radiotherapy Department, at Mohammed VI Hospital Center in Marrakech, Morocco. Results The preliminary results showed that the average age of patients was 59 ± 9 years. A proportion of 81% lived in the Marrakech-Safi region and 19% lived in four other southern regions. Among the patients, 6% were smokers, while 14% were nonsmokers and 80% were ex smokers. Following the discovery of the disease, 26% revealed that they had sleep disorders and 98% were reported to have a lack of appetite. Obesity, normal weight, and underweight were also taken as criteria to categorize the patients; thus, obese informants represented 23% of the total number, those having normal weight reached 67% and the patients having underweight represented 10%. Conclusion Sociodemographic variables and various economic characteristics were shown to have a negative impact on the lifestyle of lung cancer patients.
Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers

Background The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. Methods Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T−13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. Results The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14) μmol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P = 0.011, ρ = 0.160). The strongest correlations were observed in 87 females (P = 0.010, ρ = 0.274) and 49 males (P = 0.027, ρ = 0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P = 0.062, ρ = −0.269). Conclusion This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.
Considerations in adapting CRISPR/Cas9 in nongenetic model plant systems

The past six years have seen the rapid growth of studies of CRISPR/Cas9 in plant genome editing, a method that enormously facilitates both basic research and practical applications. Most studies have focused on genetic model species, but plant species that are not genetic models may also be economically important or biologically significant, or both. However, developing the CRISPR/Cas9 system in a nongenetic model is challenging. Here, we summarize CRISPR/Cas9 applications in 45 plant genera across 24 families and provide a reference for practical application of CRISPR in nongenetic model plant systems. Suggestions for selecting plant species and target genes are given for proof‐of‐principle CRISPR studies, and the processes of vector construction are reviewed. We recommend using transient assays to identify a desired CRISPR/Cas9 system in a nongenetic model. We then review methods of plant transformation and describe approaches, using regenerated transgenic plants, for evaluating CRISPR editing results. Lastly, potential future applications of CRISPR in nongenetic model plant species are discussed. This review provides a road map for developing CRISPR in nongenetic models, an application that holds enormous potential in plant biology.
Wide spectrum and high frequency of genomic structural variation, including transposable elements, in large double-stranded DNA viruses

Abstract Our knowledge of the diversity and frequency of genomic structural variation segregating in populations of large double-stranded (ds) DNA viruses is limited. Here, we sequenced the genome of a baculovirus (Autographa californica multiple nucleopolyhedrovirus [AcMNPV]) purified from beet armyworm (Spodoptera exigua) larvae at depths >195,000× using both short- (Illumina) and long-read (PacBio) technologies. Using a pipeline relying on hierarchical clustering of structural variants (SVs) detected in individual short- and long-reads by six variant callers, we identified a total of 1,141 SVs in AcMNPV, including 464 deletions, 443 inversions, 160 duplications, and 74 insertions. These variants are considered robust and unlikely to result from technical artifacts because they were independently detected in at least three long reads as well as at least three short reads. SVs are distributed along the entire AcMNPV genome and may involve large genomic regions (30,496 bp on average). We show that no less than 39.9 per cent of genomes carry at least one SV in AcMNPV populations, that the vast majority of SVs (75%) segregate at very low frequency (<0.01%) and that very few SVs persist after ten replication cycles, consistent with a negative impact of most SVs on AcMNPV fitness. Using short-read sequencing datasets, we then show that populations of two iridoviruses and one herpesvirus are also full of SVs, as they contain between 426 and 1,102 SVs carried by 52.4–80.1 per cent of genomes. Finally, AcMNPV long reads allowed us to identify 1,757 transposable elements (TEs) insertions, 895 of which are truncated and occur at one extremity of the reads. This further supports the role of baculoviruses as possible vectors of horizontal transfer of TEs. Altogether, we found that SVs, which evolve mostly under rapid dynamics of gain and loss in viral populations, represent an important feature in the biology of large dsDNA viruses.
Shelf‐life extension of whole shrimp using an active coating containing fish skin gelatin hydrolysates produced by a natural protease

Abstract This study was focused on shelf‐life extension of whole shrimp (Penaeus merguiensis) using an active coating containing gelatin hydrolysates. Gelatin extracted from Scomberomorus commerson skin was hydrolyzed using actinidin extracted from kiwifruit. Some important physicochemical characteristics of fish skin gelatin including viscosity, gelling and melting points, and temperatures were examined. The whole shrimp was coated with four coating agents including fish skin gelatin (FG), commercial gelatin (CG), fish skin gelatin containing 1 mg/ml fish gelatin hydrolysates (FG + GH), and commercial bovine gelatin containing 1 mg/ml fish gelatin hydrolysates (CG + GH). Chemical, microbial, and sensorial properties of samples were monitored for 12 days at 4°C with 3‐day intervals (0–12 days). The pH value of samples coated with FG + GH and CG + GH showed the lowest changes during 12 days of storage (1.68 ± 0.00 and 1.70 ± 0.09, respectively). The free fatty acid content (FFA), total volatile base nitrogen (TVB‐N), lipid oxidation, and carbonyl content of samples coated with FG + GH and CG + GH were significantly lower than that of control, CG, and FG samples. The results of this study showed that the gelatin hydrolysates could be used as a preservative costing agent for whole shrimp.