Miracle-dz/UniFAR-FTUs huggingface dataset:
EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Simple Summary Within this study we investigated the expression of EP4 in vulvar cancer, its correlation with clinic-pathological parameters, its association with overall survival, and the effect oft EP4 antagonism on vulvar cancer cells, aiming to find a prognostic and potentially targetable marker in vulvar cancer. Cox regression revealed EP4 as an independent negative prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. Further investigation of the EP4 signaling pathway and its role in the micro tumor environment in vulvar cancer could lead to a deeper understanding of the molecular mechanisms of cancer genesis. Abstract New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.
Comparative Transcriptomic Analysis of Riptortus pedestris (Hemiptera: Alydidae) to Characterize Wing Formation across All Developmental Stages

Simple Summary Riptortus pedestris is a widely distributed pest insect in East Asia that causes considerable economic losses. In this study, we applied the Illumina HiSeq6000 platform to construct and sequence the transcriptome libraries of R. pedestris during all life stages. First, a total of 60,058 unigenes were assembled from raw data, and then annotated and classified with various databases. Furthermore, different numbers of differentially expressed genes were calculated by pairwise comparisons of all life stages, and some of these DEGs were associated with various functions by GO and KEGG analysis. Additionally, a total number of 35,158 SSRs and 715,604 SNPs were identified from all the transcriptome libraries. Finally, we analyzed ten wing formation-related signaling pathways, and detected the molecular and expression characterization of five wing development-related genes by qRT-PCR for all developmental stages of R. pedestris. Collectively, all these data may pave the avenue for exploring the developmental processes of hemimetabolous insects and pest management. Abstract Riptortus pedestris (Hemiptera: Alydidae) is a major agricultural pest in East Asia that causes considerable economic losses to the soybean crop each year. However, the molecular mechanisms governing the growth and development of R. pedestris have not been fully elucidated. In this study, the Illumina HiSeq6000 platform was employed to perform de novo transcriptome assembly and determine the gene expression profiles of this species across all developmental stages, including eggs, first-, second-, third-, fourth-, and fifth-instar nymphs, and adults. In this study, a total of 60,058 unigenes were assembled from numerous raw reads, exhibiting an N50 length of 2126 bp and an average length of 1199 bp, and the unigenes were annotated and classified with various databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Gene Ontology (GO). Furthermore, various numbers of differentially expressed genes (DEGs) were calculated through pairwise comparisons of all life stages, and some of these DEGs were associated with immunity, metabolism, and development by GO and KEGG enrichment. In addition, 35,158 simple sequence repeats (SSRs) and 715,604 potential single nucleotide polymorphisms (SNPs) were identified from the seven transcriptome libraries of R. pedestris. Finally, we identified and summarized ten wing formation-related signaling pathways, and the molecular properties and expression levels of five wing development-related genes were analyzed using quantitative real-time PCR for all developmental stages of R. pedestris. Taken together, the results of this study may establish a foundation for future research investigating developmental processes and wing formation in hemimetabolous insects and may provide valuable data for pest control efforts attempting to reduce the economic damage caused by this pest.
Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases

This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70–80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells.
Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.
Repeated SARS-CoV-2 Positivity: Analysis of 123 Cases

Repeated positivity and reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a significant concern. Our study aimed to evaluate the clinical significance of repeatedly positive testing after coronavirus disease 2019 (COVID-19) recovery. We performed a systematic literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. With available individual patient data reporting on repeatedly SARS-CoV-2 positive (RSP) patients, case reports, and case series were included in this analysis. We performed a descriptive analysis of baseline characteristics of repeatedly positive cases. We assessed the cases according to the length of their polymerase chain reaction (PCR) negative interval between the two episodes. Risk factors for the severity of second episodes were evaluated. Overall, we included 123 patients with repeated positivity from 56 publications, with a mean repeated positivity length of 47.8 ± 29.9 days. Younger patients were predominant in the delayed (>90 days) recurrent positive group. Furthermore, comparing patients with RSP intervals of below 60 and above 60 days, we found that a more severe disease course can be expected if the repeated positivity interval is shorter. Severe and critical disease courses might predict future repeatedly positive severe and critical COVID-19 episodes. In conclusion, our results show that the second episode of SARS-CoV-2 positivity is more severe if it happens within 60 days after the first positive PCR. On the other hand, the second episode’s severity correlates with the first.
Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Random Sample of Inhabitants of the Katowice Region, Poland

Lack of knowledge around seroprevalence levels of COVID-19 in Poland was the reason for the implementation of a seroepidemiological study in the Katowice Region (2,100,000 inhabitants). In October–November 2020, a questionnaire examination and measurement of anti-SARS-CoV-2 IgG and IgM antibodies were performed in a random sample of the general population (n = 1167). The objectives of the study were to estimate the prevalence of IgG and IgM antibodies and to assess their host-related correlates. The prevalence of IgG seropositivity was 11.4% (95% CI: 9.5–13.2%) and IgM seropositivity was 4.6% (95% CI: 3.5–5.8%). Diagnosis of COVID-19 was found in 4.8% of subjects. A positive IgG test was statistically significantly associated with age (inverse relationship), a person’s contact with a COVID-19 patient, quarantine, and two symptoms in the past: fever and loss of smell/taste. Positive IgG tests were less prevalent in subjects who had diagnoses of arterial hypertension, diabetes, or rheumatologic disorders. IgM test positivity was associated with quarantine and loss of smell/taste only with no effect of chronic diseases found. In Poland, in the period October–November 2020, the prevalence of SARS-CoV-2 infection was larger than earlier estimates obtained in other European countries, probably reflecting the measurements obtained during the “second wave” of the epidemic.
Substrate-Induced Strain Effect on Structural and Magnetic Properties of La0.5Sr0.5CoO3 Films

We present a detailed study about the substrate-induced strain and thickness effects on the structure and magnetic properties of La0.5Sr0. 5CoO3 films. The in-plane tensile or compressive strain imposed by four different substrates configures an in-plane or out-of-plane easy axis, respectively. The presence of a soft magnetic phase at the interface is also conditioned by the type of strain. The obtained results are discussed in terms of the different anisotropies that participate and control the final magnetic behavior. The relevance of these results lies in the feasibility of La0.5Sr0. 5CoO3 in memory applications and spintronic devices.
Metabolic Syndrome and Dietary Habits in Hospitalized Patients with Schizophrenia: A Cross-Sectional Study

Background and Objectives: The true prevalence of metabolic syndrome (MetS) and the reason for it being higher in patients with schizophrenia when compared to general population have not yet been fully determined. Although being considered as one of the major causes, currently there are limited findings regarding differences in dietary patterns of schizophrenic patients with and without MetS. The present study aimed to determine the prevalence of MetS among hospitalized patients with schizophrenia, to investigate the differences in socio-demographic, clinical, and lifestyle characteristics between participants with and without MetS, with the special emphasis being put on their dietary habits, and to ascertain the correlation between dietary habits and MetS components. Materials and Methods: A cross-sectional study included 259 hospitalized patients with schizophrenia aged ≥ 18 years. All participants underwent basic anthropometric measurements, blood sampling and blood pressure assessment, and provided relevant socio-demographic and lifestyle information. The presence of MetS was determined according to the Joint Interim Statement definition and dietary habits were assessed using a non-quantitative food frequency questionnaire. Results: The overall prevalence of MetS was 47.9%. No socio-demographic or lifestyle differences were found between participants with and without MetS. A large number of participants (42.9%) reported consuming carbonated soft drinks on a daily basis. Daily frequency of fruit (11.6%) and vegetables intake (29.3%) was far below recommended. Dietary habits of participants with and without MetS did not significantly differ, while consumption frequencies of some of the studied food and beverage items and groups significantly correlated with certain MetS components (such as statistically significant positive correlation between cured meat products consumption frequency and waist circumference, as well as between red meat consumption frequency and systolic blood pressure). Conclusions: The concept of the present study did not allow us to distinguish to what extent the participants’ dietary habits were influenced by independent procurement of food products, nor has it allowed us to quantify the portion sizes of consumed food and beverage items and groups. Nevertheless, the findings indicate the need for early identification of individuals with high MetS risk and for the incorporation of nutritional support programs into hospital treatment of patients with schizophrenia.
Discrimination of Gardnerella Species by Combining MALDI-TOF Protein Profile, Chaperonin cpn60 Sequences, and Phenotypic Characteristics

The description of Gardnerella vaginalis was recently updated and three new species, including nine genome species within Gardnerella, were defined using whole genome sequences and matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. A fast and simple method based on readily available techniques would be of immense use to identify Gardnerella species in research and clinical practice. Here we show that 34 previously characterized Gardnerella isolates were assigned to the species using partial chaperonin cpn60 sequences. The MALDI Biotyper from Bruker Daltonik GmbH demonstrated the capability to differentiate the phylogenetically diverse groups composed of G. vaginalis/G. piotii and G. leopoldii/G. swidsinskii. Among the phenotypic properties that characterize Gardnerella species are sialidase and β-galactosidase activities. Our data confirmed that the NanH3 enzyme is responsible for sialidase activity in Gardnerella spp. isolates. Almost all G. piotii isolates displayed a sialidase positive phenotype, whereas the majority of G. vaginalis strains were sialidase negative. G. leopoldii and G. swidskinskii displayed a sialidase negative phenotype. β-galactosidase is produced exclusively in G. vaginalis strains. Earlier determined phenotypic characteristics associated with virulence of Gardnerella isolates now assigned to the defined species may provide insights on how diverse species contribute to shaping the vaginal microbiome.
Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y12 could serve as components of dual anti-platelet therapy. We have found that a selective A2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y12 inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.
The Mechanisms of the Anti-Inflammatory and Anti-Apoptotic Effects of Omega-3 Polyunsaturated Fatty Acids during Methotrexate-Induced Intestinal Damage in Cell Line and in a Rat Model

Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.
Rare Forms of Lipomatosis: Dercum’s Disease and Roch-Leri Mesosomatous Lipomatosis

In contrast to obesity, which is very frequent, lipomatosis and lipodystrophy syndromes are rare diseases of adipose tissue. Lipodystrophy syndromes are characterized by metabolic abnormalities associated with partial or generalized lipoatrophy. Lipomatosis is defined by the presence of several body lipomas without lipoatrophy. Dercum’s disease (DD) and Roch-Leri mesosomatous lipomatosis (RLML) are rare and poorly characterized forms of lipomatosis. They have raised little clinical interest despite the non-negligible consequences of DD on quality of life. The main clinical presentation of these diseases includes multiple lipomas, which are painful in DD (in contrast to RLML). The two diseases are frequently associated with obesity and metabolic syndrome, with hypertension, diabetes, or dyslipidemia. The long-term course of the diseases remains poorly described. DD affects mainly women, whereas RLML mostly affects men. In both diseases lipomas are found on the back and thighs, as well as on the abdomen in DD and the forearms in RLML. The painful lipomas tend to recur after surgery in DD (in contrast to RLML). Most cases are sporadic. No specific treatment has been identified, as the pathophysiology remains unknown. Nevertheless, low-grade fat inflammation and specific abnormalities such as hyperbasophilia deserve further investigation. The aim of this review is to analyze the available literature on the topic.
Identification of Breast Cancer Subtype-Specific Biomarkers by Integrating Copy Number Alterations and Gene Expression Profiles

Background and Objectives: Breast cancer is a heterogeneous disease categorized into four subtypes. Previous studies have shown that copy number alterations of several genes are implicated with the development and progression of many cancers. This study evaluates the effects of DNA copy number alterations on gene expression levels in different breast cancer subtypes. Materials and Methods: We performed a computational analysis integrating copy number alterations and gene expression profiles in 1024 breast cancer samples grouped into four molecular subtypes: luminal A, luminal B, HER2, and basal. Results: Our analyses identified several genes correlated in all subtypes such as KIAA1967 and MCPH1. In addition, several subtype-specific genes that showed a significant correlation between copy number and gene expression profiles were detected: SMARCB1, AZIN1, MTDH in luminal A, PPP2R5E, APEX1, GCN5 in luminal B, TNFAIP1, PCYT2, DIABLO in HER2, and FAM175B, SENP5, SCAF1 in basal subtype. Conclusions: This study showed that computational analyses integrating copy number and gene expression can contribute to unveil the molecular mechanisms of cancer and identify new subtype-specific biomarkers.