Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular Endothelial Cells: Heterogeneity and Targeting Approaches

Forming the inner layer of the vascular system, endothelial cells (ECs) facilitate a multitude of crucial physiological processes throughout the body. Vascular ECs enable the vessel wall passage of nutrients and diffusion of oxygen from the blood into adjacent cellular structures. ECs regulate vascular tone and blood coagulation as well as adhesion and transmigration of circulating cells. The multitude of EC functions is reflected by tremendous cellular diversity. Vascular ECs can form extremely tight barriers, thereby restricting the passage of xenobiotics or immune cell invasion, whereas, in other organ systems, the endothelial layer is fenestrated (e.g., glomeruli in the kidney), or discontinuous (e.g., liver sinusoids) and less dense to allow for rapid molecular exchange. ECs not only differ between organs or vascular systems, they also change along the vascular tree and specialized subpopulations of ECs can be found within the capillaries of a single organ. Molecular tools that enable selective vascular targeting are helpful to experimentally dissect the role of distinct EC populations, to improve molecular imaging and pave the way for novel treatment options for vascular diseases. This review provides an overview of endothelial diversity and highlights the most successful methods for selective targeting of distinct EC subpopulations.
Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.
Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies

Simple Summary Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. With a limited number of therapeutic options available and a lack of effective anti-tumoral immune responses by the therapies, there is a dire need to search for new translational treatment options. Photodynamic Therapy (PDT), in recent years, has proven itself as an effective anti-cancer therapy. In this review, we discuss the mechanism of PDT, its evolution as an anti-cancer modality, with a special focus on HCC. We also highlight the immune response generated by PDT and how it could be essential in HCC treatment. Finally, we proposed an intraoperative procedure for the treatment of HCC by combining hepatectomy with PDT. Abstract Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment.
Effects of Manganese on Genomic Integrity in the Multicellular Model Organism Caenorhabditis elegans

Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.
A Heuristic and Data Mining Model for Predicting Broiler House Environment Suitability

Simple Summary The broiler housing control environment now is primarily based on the rearing temperature. The current study proposes two decision-tree models using flock-based and environmental data such as ambient temperature, air velocity, relative humidity, and ammonia concentration. Data from commercial broiler farms were collected and analyzed. An exploratory analysis employed the environmental variables, and a heuristic approach was used to develop a final dataset based on ammonia concentration’s impact on broiler production. The output models were related to dry bulb temperature, relative humidity, air velocity, and ammonia concentration arrays. The resulting trees classify the most suitable commercial broiler environment. Such variable combinations might help to improve environmental control in broiler houses. Abstract The proper combination of environment and flock-based variables plays a critical role in broiler production. However, the housing environment control is mainly focused on temperature monitoring during the broiler growth process. The present study developed a novel predictive model to predict the broiler (Gallus gallus domesticus) rearing conditions’ suitability using a data-mining process centered on flock-based and environmental variables. Data were recorded inside four commercial controlled environment broiler houses. The data analysis was conducted in three steps. First, we performed an exploratory and descriptive analysis of the environmental data. In the second step, we labeled the target variable that led to a specific broiler-rearing scenario depending on the age of the birds, the environmental dry-bulb temperature and relative humidity, the ammonia concentration, and the ventilation rate. The output (final rearing condition) was discretized into four categories (‘Excellent’, ‘Good’, ‘Moderate’, and ‘Inappropriate’). In the third step, we used the dataset to develop tree models using the data-mining process. The random-tree model only presented accuracy for predicting the ‘Excellent’ and ‘Moderate’ rearing conditions. The decision-tree model had high accuracy and indicated that broiler age, relative humidity, and ammonia concentration play a critical role in proper rearing conditions. Using a large amount of data allows the data-mining approach to building up ‘if–then’ rules that indicate suitable environmental control decision-making by broiler farmers.
Evaluation of a Murine Model for Testing Antimicrobial Implant Materials in the Blood Circulation System

Medical device-related infections are becoming a steadily increasing challenge for the health care system regarding the difficulties in the clinical treatment. In particular, cardiovascular implant infections, catheter-related infections, as well as infective endocarditis are associated with high morbidity and mortality risks for the patients. Antimicrobial materials may help to prevent medical device-associated infections and supplement the currently available therapies. In this study, we present an easy-to-handle and simplified in vivo model to test antimicrobial materials in the bloodstream of mice. The model system is composed of the implantation of a bacteria-laden micro-stent scaffold into the murine tail vein. Our model enables the simulation of catheter-related infections as well as the development of infective endocarditis specific pathologies in combination with material testing. Furthermore, this in vivo model can cover two phases of the biofilm formation, including both the local tissue response to the bacterial biofilm and the systemic inflammatory response against circulating bacteria in the bloodstream that detached from a mature biofilm.
Microbial Therapeutics in Neurocognitive and Psychiatric Disorders

Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.
Mambalgin-2 Inhibits Growth, Migration, and Invasion of Metastatic Melanoma Cells by Targeting the Channels Containing an ASIC1a Subunit Whose Up-Regulation Correlates with Poor Survival Prognosis

Melanoma is an aggressive cancer characterized by the acidification of the extracellular environment. Here, we showed for the first time that extracellular media acidification increases proliferation, migration, and invasion of patient-derived metastatic melanoma cells and up-regulates cell-surface expression of acid-sensitive channels containing the ASIC1a, α-ENaC, and γ-ENaC subunits. No influence of media acidification on these processes was found in normal keratinocytes. To control metastatic melanoma progression associated with the ASIC1a up-regulation, we proposed the ASIC1a inhibitor, -mambalgin-2 from Dendpoaspis polylepis venom. Recombinant analog of mambalgin-2 cancelled acidification-induced proliferation, migration, and invasion of metastatic melanoma cells, promoted apoptosis, and down-regulated cell-surface expression of prooncogenic factors CD44 and Frizzled 4 and phosphorylation of transcription factor SNAI. Confocal microscopy and affinity purification revealed that mambalgin-2 interacts with heterotrimeric ASIC1a/α-ENaC/γ-ENaC channels on the surface of metastatic melanoma cells. Using the mutant variant of mambalgin-2 with reduced activity toward ASIC1a, we confirmed that the principal molecular target of mambalgin-2 in melanoma cells is the ASIC1a subunit. Bioinformatic analysis confirmed up-regulation of the ASIC1 expression as a marker of poor survival prognosis for patients with metastatic melanoma. Thus, targeting ASIC1a by drugs such as mambalgin-2 could be a promising strategy for metastatic melanoma treatment.
Neuroplastin in Neuropsychiatric Diseases

Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system.
Effects of Using Corn Dried Distillers’ Grains with Solubles (cDDGS) as a Partial Replacement for Soybean Meal on the Outcomes of Pig Fattening, Pork Slaughter Value and Quality

Simple Summary Soybean meal is the principal component of the diets for fattener pigs; however, there is a constant need for alternative, inexpensive, preferably non-GMO (genetic modified organisms) protein sources in swine nutrition. Corn dried distillers’ grains with solubles (cDDGS), by-products of ethanol and bioethanol production, are one such alternative. Due to their chemical composition, they cannot completely replace soybean meal; however, even relatively small additions of cDDGS may decrease the cost of feeding and increase profitability of pig production. In this study, the pigs were fed two different diets: control (cereal–soybean meal-based) or cDDGS (with soybean meal partially replaced with cDGGS). The growth performance as well as carcass and meat quality traits of fatteners fed cDGGS-containing diets did not differ from those of their respective controls. However, the addition of even 15% of cDDGS did result in lower production costs and increased the profitability of pig fattening. Abstract The present study set out to determine the effects of incorporating cDDGS into starter, grower, and finisher diets (containing 5%, 10%, and 15% of cDDGS, respectively) on growth performance, carcass and meat quality, and cost effectiveness of pig fattening. Sixty-four pigs (mean body weight of 15.0 ± 2.1 kg) were divided into two groups (n = 32) and fed a control diet (cereal–soybean meal-based) or cDGGS-containing diets (with soybean meal partially replaced with cDDGS). Live weights of pigs as well as weight gains/daily weight gains across all fattening phases did not differ between the two groups of fattener pigs studied (p > 0.05). Addition of cDDGS decreased feed intake per pig during the grower (p < 0.05) and finisher (p < 0.01) phases, and, as a result, throughout the entire fattening period (254 vs. 245 kg for control and cDDGS groups, respectively; p < 0.01). The feed conversion ratio (FCR) for the entire fattening period was significantly less for cDDGS-fed fatteners (2.77) than for controls (2.91; p < 0.05). Carcass weights, fat thickness, and meatiness did not vary between the two groups of animals (p > 0.05). Loin depth was greater in the cDDGS group by ~5 mm (p < 0.05). Slaughter value was higher for the cDDGS group (76.1% vs. 77.0%, p < 0.05). The total cost of fattening and total cost of 1 kg of body weight decreased in cDDGS compared with the control subset of fatteners by ~7% and 8% during the grower and finisher phases, respectively (p < 0.01). The simplified direct surplus per pig was approximately 63% higher for the cDDGS group. Our results indicate that even moderate inclusion of cDDGS to concentrate mixtures (or a partial replacement of soybean meal with cDDGS) may improve FCR without any substantial changes in meat and back fat characteristics as well as significantly decrease the cost of feeding and increase the profitability of pig production.
Body Fat Plays an Important Role in of Bioimpedance Spectroscopy-Based Dry Weight Measurement Error for Patients with Hemodialysis

Accurate dry weight (DW) estimation is important for hemodialysis patients. Although bioimpedance spectroscopy (BIS) is commonly used to measure DW, the BIS-based DW frequently differs from the clinical DW. We analyzed the characteristics of patients whose BIS-based DWs were over- and underestimated. In this retrospective cohort study, we evaluated 1555 patients undergoing maintenance hemodialysis in Chungnam National University Hospital. The gap (DWCP-BIS) was calculated by comparing the BIS and clinical DWs. We analyzed the clinical characteristics of patients with positive (n = 835) and negative (n = 720) gaps. Compared with other patients, the DWCP-BIS-positive group had higher extracellular water (ECW) level and extracellular/intracellular water index (E/I) and had lower weight, body mass index (BMI), lean tissue index (LTI), fat tissue index (FTI), fat mass (FAT), and adipose tissue mass (ATM). The DWCP-BIS-negative group exhibited elevated BMI, FTI, FAT, and ATM; however, it had lower height, ECW, and E/I. Linear regression analysis revealed that FAT significantly predicted DWCP accuracy. The clinical DW of patients with a low fat mass tended to be underestimated, while the clinical DW of patients with comparatively large fat reserves tended to be overestimated. These characteristics will aid in the reduction of BIS-based DW errors.
Potential Probiotic Enterococcus faecium OV3-6 and Its Bioactive Peptide as Alternative Bio-Preservation

Probiotic Enterococcus faecium OV3-6 and its secreted active peptide were characterized and investigated. The strain survived in simulated gastric and small intestinal conditions at 88.16% and 94.33%, respectively. The safety assessment revealed that the strain was shown α-hemolysis and susceptible to most clinically relevant antibiotics, but intermediate sensitivity to erythromycin and kanamycin was found. It does not harbor any virulence genes except for the efaAfm gene. Both of its living cells and the cell-free supernatants (CFS) of the strain significantly reduced the adhesion of E. coli and S. Typhi on Caco-2 cells. The strain can regulate the secretion of pro and inflammatory cytokines, IL-6 and IL-12 and induce the secretion of anti-inflammatory IL-10 of the Caco-2 cell. The strain can prevent the growth of Gram-positive strains belonging to the genera Bacillus, Carnobacterium, Listeria, and Staphylococcus. It also presented the entP gene that involves the production of bacteriocin named enterocin P. The antimicrobial peptide was matched 40% with 50S ribosomal proteins L29 (7.325 kDa), as revealed by LC-MS/MS. This active peptide exhibits heat stability, is stable over a wide pH range of 2−10, and maintains its activity at −20 and 4 °C for 12 weeks of storage. Altogether, E. faecium OV3-6 thus has potential for consideration as a probiotic and bio-preservative for applied use as a fermented food starter culture and in functional food or feed industries.
Reading and Oral Language Skills in Children With Developmental Language Disorder: Influence of Socioeconomic, Educational, and Family Variables

The Developmental Language Disorder (DLD) is a delay in language skills that cannot be explained by sensory or cognitive difficulties. Currently, there are limited studies that analyze how socioeconomic, educational, and family variables influence reading skills of Spanish-speaking children with DLD at school. This study identifies how oral language performance and reading skills of children with DLD are linked to socioeconomic, educational, and family factors. Oral language, phonological awareness and reading abilities were assessed in a sample of 15 children diagnosed with DLD and their controls by age and gender. Children's parents answered a Likert scale questionnaire inquiring about some aspects related to the family's socioeconomic status, mothers' educational level, family support, academic average, and repetition of school years of the participants. The results indicate that children with DLD have a lower performance in phonological awareness tasks as well as in reading abilities. There is also a direct relationship between their performance in language and reading skills and variables as mother's educational level and family support. Likewise, children in the sample have a lower academic average as well as a higher school year repetition rate interfering in their academic life. Educational implications of these findings and a discussion on possible causality axes and protective factors that contributes to support this population are presented.