Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNAs Regulating Tumor and Immune Cell Interactions in the Prediction of Relapse in Early Stage Breast Cancer

MicroRNAs (miRNAs) are involved in the regulation of immune response and hold an important role in tumor immune escape. We investigated the differential expression of the immunomodulatory miR-10b, miR-19a, miR-20a, miR-126, and miR-155 in the plasma of healthy women and patients with early stage breast cancer and interrogated their role in the prediction of patients’ relapse. Blood samples were obtained from healthy women (n = 20) and patients with early stage breast cancer (n = 140) before adjuvant chemotherapy. Plasma miRNA expression levels were assessed by RT-qPCR. Relapse predicting models were developed using binary logistic regression and receiver operating curves (ROC) were constructed to determine miRNA sensitivity and specificity. Only miR-155 expression was lower in patients compared with healthy women (p = 0.023), whereas miR-155 and miR-10b were lower in patients who relapsed compared with healthy women (p = 0.039 and p = 0.002, respectively). MiR-155 expression combined with axillary lymph node infiltration and tumor grade demonstrated increased capability in distinguishing relapsed from non-relapsed patients [(area under the curve, (AUC = 0.861; p < 0.001)]. Combined miR-19a and miR-20a expression had the highest performance in discriminating patients with early relapse (AUC = 0.816; p < 0.001). Finally, miR-10b in combination with lymph node status and grade had the highest accuracy to discriminate patients with late relapse (AUC = 0.971; p < 0.001). The robustness of the relapse predicting models was further confirmed in a 10-fold cross validation. Deregulation of circulating miRNAs involved in tumor-immune interactions may predict relapse in early stage breast cancer. Their successful clinical integration could potentially address the significance challenge of treatment escalation or de-escalation according to the risk of recurrence.
Fluorescently Labeled Cellulose Nanofibers for Environmental Health and Safety Studies

An optimal methodology for locating and tracking cellulose nanofibers (CNFs) in vitro and in vivo is crucial to evaluate the environmental health and safety properties of these nanomaterials. Here, we report the use of a new boron-dipyrromethene (BODIPY) reactive fluorescent probe, meso-DichlorotriazineEthyl BODIPY (mDTEB), tailor-made for labeling CNFs used in simulated or in vivo ingestion exposure studies. Time-correlated single photon counting (TCSPC) fluorescence lifetime imaging microscopy (FLIM) was used to confirm covalent attachment and purity of mDTEB-labeled CNFs. The photoluminescence properties of mDTEB-labeled CNFs, characterized using fluorescence spectroscopy, include excellent stability over a wide pH range (pH2 to pH10) and high quantum yield, which provides detection at low (μM) concentrations. FLIM analysis also showed that lignin-like impurities present on the CNF reduce the fluorescence of the mDTEB-labeled CNF, via quenching. Therefore, the chemical composition and the methods of CNF production affect subsequent studies. An in vitro triculture, small intestinal, epithelial model was used to assess the toxicity of ingested mDTEB-labeled CNFs. Zebrafish (Danio rerio) were used to assess in vivo environmental toxicity studies. No cytotoxicity was observed for CNFs, or mDTEB-labeled CNFs, either in the triculture cells or in the zebrafish embryos.
Connectivity of Edaphic and Endolithic Microbial Niches in Cold Mountain Desert of Eastern Pamir (Tajikistan)

Simple Summary Microbial communities play a significant role in the functioning of the ecosystem in the cold mountain desert of Eastern Pamir, a region that is characterized by extreme environments with limited nutrient and water availability and sparse vegetation. This study aims to investigate the taxonomic composition and structure of bacterial endolithic (rock matrix colonizing) assemblages and soil-inhabiting communities that occur in the Eastern Pamir Mountains, and to compare the composition and structure of both types of communities looking for general patterns and trying to identify the connectivity between these types of microbial assemblages. The taxonomic composition of Pamirian endolithic communities and soil-inhabiting microbial consortia (biocrust communities) exhibit similarities to communities from cold and hot deserts, but they also harbor taxa, which are possibly novel species or which, so far, lack reference sequences in the databases. The endolithic communities occurring in three subregions of Eastern Pamir are characterized by high heterogeneity and cannot be grouped according to the subregion, while the distribution of Cyanobacteria in the soil crusts demonstrates the similarities between the communities within the subregion reflecting regional differences. We also found connectivity between both habitats concerning the occurrence the same taxa (e.g., Cyanobacteria). Abstract Microbial communities found in arid environments are commonly represented by biological soil crusts (BSCs) and endolithic assemblages. There is still limited knowledge concerning endoliths and BSCs occurring in the cold mountain desert of Pamir. The aim of the study was to investigate the composition and structure of endolithic bacterial communities in comparison to surrounding BSCs in three subregions of the Eastern Pamir (Tajikistan). The endolithic and BSC communities were studied using culture-independent and culture-dependent techniques. The structure of the endolithic bacterial communities can be characterized as Actinobacteria–Proteobacteria–Bacteroidetes–Chloroflexi–Cyanobacteria, while the BSCs’ can be described as Proteobacteria–Actinobacteria–Bacteroidetes–Cyanobacteria assemblages with low representation of other bacteria. The endolithic cyanobacterial communities were characterized by the high percentage of Chroococcidiopsaceae, Nodosilineaceae, Nostocaceae and Thermosynechococcaceae, while in the BSCs were dominated by Nodosilineaceae, Phormidiaceae and Nostocaceae. The analysis of 16S rRNA genes of the cyanobacterial cultures revealed the presence of possibly novel species of Chroococcidiopsis, Gloeocapsopsis and Wilmottia. Despite the niches’ specificity, which is related to the influence of microenvironment factors on the composition and structure of endolithic communities, our results illustrate the interrelation between the endoliths and the surrounding BSCs in some regions. The structure of cyanobacterial communities from BSC was the only one to demonstrate some subregional differences.
Deficiency of NEIL3 Enhances the Chemotherapy Resistance of Prostate Cancer

Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.
The Formation of Mn-Ce Oxide Catalysts for CO Oxidation by Oxalate Route: The Role of Manganese Content

The Mn-Ce oxide catalysts active in the oxidation of CO were studied by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR), transition electron microscopy (TEM), energy dispersive X-Ray (EDX), and a differential dissolution technique. The Mn-Ce catalysts were prepared by thermal decomposition of oxalates by varying the Mn:Ce ratio. The nanocrystalline oxides with a fluorite structure and particle sizes of 4–6 nm were formed. The introduction of manganese led to a reduction of the oxide particle size, a decrease in the surface area, and the formation of a MnyCe1−yO2−δ solid solution. An increase in the manganese content resulted in the formation of manganese oxides such as Mn2O3, Mn3O4, and Mn5O8. The catalytic activity as a function of the manganese content had a volcano-like shape. The best catalytic performance was exhibited by the catalyst containing ca. 50 at. % Mn due to the high specific surface area, the formation of the solid solution, and the maximum content of the solid solution.
An Exaggerated Rise in Pulmonary Artery Pressure in a High-Altitude Dweller during the Cold Season

Chronic hypoxia-induced sustained pulmonary vasoconstriction and vascular remodeling lead to mild-to-moderate elevation of pulmonary artery pressure in high-altitude residents. However, in some of them, severe pulmonary hypertension may develop. Besides hypoxia, high-altitude residents also face other environmental challenges such as low ambient temperatures. We describe a case of a 49-year-old woman of Kyrgyz ethnicity with abnormally increased pulmonary artery pressure, revealed by Doppler echocardiography. Significantly elevated pulmonary artery pressure was detected in late winter and this was not associated with right ventricular hypertrophy or right ventricular dysfunction. Repeat echocardiography performed in late summer disclosed a significant attenuation of pulmonary artery pressure elevation, with no changes in right ventricular performance parameters. This case illustrates that, in susceptible individuals, long-term cold exposure could induce an abnormal pulmonary artery pressure rise, which can be reversed during warm seasons as in our patient. In certain circumstances, however, additional factors could contribute to a sustained pulmonary artery pressure increase and the development of persistent pulmonary hypertension, which often leads to right heart failure and premature death.
Therapeutic Efficacy of a Novel Acetylated Tetrapeptide in Animal Models of Age-Related Macular Degeneration

It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pathway. In this study, we report that a modified tetrapeptide (Ac-RLYE) showed improved anti-choroidal neovascularization (CNV) efficacy in a number of animal models of neovascular age-related macular degeneration (AMD) which include rat, rabbit, and minipig. The preventive and therapeutic in vivo efficacy of Ac-RLYE via following intravitreal administration was determined to be either similar or superior to that of ranibizumab and aflibercept. Assessment of the intraocular pharmacokinetic and toxicokinetic properties of Ac-RLYE in rabbits demonstrated that it rapidly reached the retina with minimal systemic exposure after a single intravitreal dose, and it did not accumulate in plasma during repetitive dosing (bi-weekly for 14 weeks). Our results suggested that Ac-RLYE has a great potential for an alternative therapeutics for neovascular (wet) AMD. Since the amino acids in human VEGFR-2 targeted by Ac-RLYE are conserved among the animals employed in this study, the therapeutic efficacies of Ac-RLYE evaluated in those animals are predicted to be observed in human patients suffering from retinal degenerative diseases.
Clinical Applications of Genomic Alterations in ATLL: Predictive Markers and Therapeutic Targets

Simple Summary In this review paper, we aim to summarize recent findings of genomic alterations found in adult T-cell leukemia/lymphoma (ATLL), which is an incurable disease induced by a virus; human T-cell leukemia virus type 1 (HTLV-1). Genomic alterations of ATLL have been comprehensively analyzed and the identified alterations and HTLV-1 infection synergistically act for ATLL development. As HTLV-1 is an endemic disease, ATLL frequently occurs in the endemic areas. Current clinicogenomic analyses suggest the existence of regional difference in ATLL pathophysiology. From a clinical perspective, several studies identified alterations that act as predictive markers and that a part of the alterations can be targetable in ATLL. The alterations can be leveraged to improve ATLL prognosis. Abstract Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma (PTCL) caused by human T-cell leukemia virus type 1 (HTLV-1). Recent comprehensive genomic analyses have revealed the genomic landscape. One of the important findings of genomic alterations in ATLL is that almost all alterations are subclonal, suggesting that therapeutic strategies targeting a genomic alteration will result in partial effects. Among the identified alterations, genes involved in T-cell receptor signaling and immune escape mechanisms, such as PLCG1, CARD11, and PD-L1 (also known as CD274), are characteristic of ATLL alterations. From a geographic perspective, ATLL patients in Caribbean islands tend to be younger than those in Japan and the landscape differs between the two areas. Additionally, young Japanese ATLL patients frequently have CD28 fusions, compared with unselected Japanese cases. From a clinical perspective, PD-L1 amplification is an independent prognostic factor among every subtype of ATLL case. Recently, genomic analysis using deep sequencing identified a pre-ATLL clone with ATLL-common mutations in HTLV-1 carriers before development, indicating that genomic analysis can stratify cases based on the risks of development and mortality. In addition to genomic alterations, targetable super-enhancers have been identified in ATLL. These data can be leveraged to improve the prognosis of ATLL.
Hypothalamic GHR—SIRT1 Axis in Fasting

Many aspects of physiological functions are controlled by the hypothalamus, a brain region that connects the neuroendocrine system to whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions known to participate in the regulation of feeding and whole-body energy homeostasis. Sirtuin 1 (SIRT1) is the most conserved mamma-lian nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that plays a key role in controlling life span and sensing nutrient availability in the hypothalamus in response to caloric restriction. However, the interaction between GHR signaling and SIRT1 in the hypothal-amus is not established. In the arcuate nucleus (ARC) of the hypothalamus, the anorexigenic proopiomelanocortin (POMC)-expressing neurons and the orexigenic agouti-related protein (AgRP)-expressing neurons are the major regulators of feeding and energy expenditure. We show that in the ARC, the majority of GHR-expressing neurons also express SIRT1 and respond to fasting by upregulating SIRT1 expression. Accordingly, hypothalamic upregulation of SIRT1 in response to fasting is blunted in animals with GHR deletion in the AgRP neurons (AgRPEYFPΔGHR). Our data thus reveal a novel interaction between GH and SIRT1 in responses to fasting.
Nutritional Psychiatry: How Diet Affects Brain through Gut Microbiota

Nutritional sciences have been recognized as being of paramount importance for the prevention of non-communicable diseases. Among others, mental health disorders have been hypothesized to be influenced by dietary risk through a variety of molecular mechanisms. The improvements in the technology and implementation of-omics sciences in terms of nutrition have created the possibility of studying the relation between diet, gut microbiota and mental health. The gut–brain–axis represents the core rationale setting the stage for a relatively new discipline of study defined as “nutritional psychiatry”. Research on this matter will help to better understand the relation between food and mood, sleep quality, cognition, and mental health in general.
Update on Genetics of Primary Aldosteronism

Primary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5–10% among patients with hypertension. PA is mainly classified into two subtypes: aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. Recent developments in genetic analysis have facilitated the discovery of mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, CLCN2, and CTNNB1 in sporadic or familial forms of PA in the last decade. These findings have greatly advanced our understanding of the mechanism of excess aldosterone synthesis, particularly in APA. Most of the causative genes encode ion channels or pumps, and their mutations lead to depolarization of the cell membrane due to impairment of ion transport. Depolarization activates voltage-gated Ca2+ channels and intracellular calcium signaling and promotes the transcription of aldosterone synthase, resulting in overproduction of aldosterone. In this article, we review recent findings on the genetic and molecular mechanisms of PA.
A Systematic Review for Effective Preventive Public Education of Respiratory Infection

The present study aimed to systematically review to find the best available evidence on the efficacy of non-pharmaceutical interventions that have been used in the community so far. Through eight electronic journal database, 9 articles met our inclusion Participants, Intervention, Control, Outcomes, and Study Design (PICOS) criteria based on medical symptoms, interventions, and improvements. In general, interventions included hand hygiene, mask use, health education such as cough etiquette, hand washing and sanitizer methods. In addition, exercise and meditation were performed to improve immunity. As a result, the number of incidents and absences related to respiratory infections were reduced, the frequency and method of handwashing improved, and there were also positive effects in knowledge, attitude/perception, and performance. We concluded that it is necessary to create an environment and systematic support so that organizations or governments can determine healthy behavior at the same time as an individual approach. Furthermore, the follow-up for evaluating the effectiveness of interventions and the monitoring period should be included during the study, consequently resulting in having an opportunity to continuously remind people about health behavior. The community provides information on various types of non-pharmaceutical intervention to maintain healthy management and lifestyles in the public.
Elevation of Pro-Inflammatory Cytokine Levels Following Intra-Articular Fractures—A Systematic Review

Abstract Introduction: Intra-articular fractures are a major cause of post-traumatic osteoarthritis (PTOA). Despite adequate surgical treatment, the long-term risk for PTOA is high. Previous studies reported that joint injuries initiate an inflammatory cascade characterized by an elevation of synovial pro-inflammatory cytokines, which can lead to cartilage degradation and PTOA development. This review summarizes the literature on the post-injury regulation of pro-inflammatory cytokines and the markers of cartilage destruction in patients suffering from intra-articular fractures. Methods: We searched Medline, Embase, and Cochrane databases (1960–February 2020) and included studies that were performed on human participants, and we included control groups. Two investigators assessed the quality of the included studies using Covidence and the Newcastle–Ottawa Scale. Results: Based on the surveyed literature, several synovial pro-inflammatory cytokines, including interleukins (IL)-1β, IL-2, IL-6, IL-8, IL-12p70, interferon-y, and tumor necrosis factor-α, were significantly elevated in patients suffering from intra-articular fractures compared to the control groups. A simultaneous elevation of anti-inflammatory cytokines such as IL-10 and IL-1RA was also observed. In contrast, IL-13, CTX-II, and aggrecan concentrations did not differ significantly between the compared cohorts. Conclusions: Overall, intra-articular fractures are associated with an increase in inflammation-related synovial cytokines. However, more standardized studies which focus on the ratio of pro- and anti-inflammatory cytokines at different time points are needed.
Outer Membrane Vesicle Production by Helicobacter pylori Represents an Approach for the Delivery of Virulence Factors CagA, VacA and UreA into Human Gastric Adenocarcinoma (AGS) Cells

Helicobacter pylori infection is the etiology of several gastric-related diseases including gastric cancer. Cytotoxin associated gene A (CagA), vacuolating cytotoxin A (VacA) and α-subunit of urease (UreA) are three major virulence factors of H. pylori, and each of them has a distinct entry pathway and pathogenic mechanism during bacterial infection. H. pylori can shed outer membrane vesicles (OMVs). Therefore, it would be interesting to explore the production kinetics of H. pylori OMVs and its connection with the entry of key virulence factors into host cells. Here, we isolated OMVs from H. pylori 26,695 strain and characterized their properties and interaction kinetics with human gastric adenocarcinoma (AGS) cells. We found that the generation of OMVs and the presence of CagA, VacA and UreA in OMVs were a lasting event throughout different phases of bacterial growth. H. pylori OMVs entered AGS cells mainly through macropinocytosis/phagocytosis. Furthermore, CagA, VacA and UreA could enter AGS cells via OMVs and the treatment with H. pylori OMVs would cause cell death. Comparison of H. pylori 26,695 and clinical strains suggested that the production and characteristics of OMVs are not only limited to laboratory strains commonly in use, but a general phenomenon to most H. pylori strains.