Miracle-dz/UniFAR-FTUs huggingface dataset:
SPRAY DRYING INVESTIGATIONS ON MEDICINAL PLANT BASED PHARMACEUTICAL PRODUCTS

In the paper we report about spray drying investigations on medicinal herb extracts. We investigated the production technologies of up-to-date pharmaceutical products and natural raw materials of drugs. In this paper we report in detail about spray drying investigation of some medicinal plants and about how to define the operational features of these products. In our tests we could find that the extract of camomile, rose hip and lime blossom can be processed well by spray drying. We worked out the main operational features to be applied when using spray drying under industrial circumstances.
High-Density Lipoprotein Functionality as a New Pharmacological Target on Cardiovascular Disease: Unifying Mechanism That Explains High-Density Lipoprotein Protection Toward the Progression of Atherosclerosis

Abstract: The formation of the atherosclerotic plaque that is characterized by the accumulation of abnormal amounts of cholesterol-loaded macrophages in the artery wall is mediated by both inflammatory events and alterations of lipid/lipoprotein metabolism. Reverse transport of cholesterol opposes the formation and development of atherosclerotic plaque by promoting high density lipoprotein (HDL)-mediated removal of cholesterol from peripheral macrophages and its delivery back to the liver for excretion into the bile. Although an inverse association between HDL plasma levels and the risk of cardiovascular disease (CVD) has been demonstrated over the years, several studies have recently shown that the antiatherogenic functions of HDL seem to be mediated by their functionality, not always associated with their plasma concentrations. Therefore, assessment of HDL function, evaluated as the capacity to promote cell cholesterol efflux, may offer a better prediction of CVD than HDL levels alone. In agreement with this idea, it has recently been shown that the assessment of serum cholesterol efflux capacity (CEC), as a metric of HDL functionality, may represent a predictor of atherosclerosis extent in humans. The purpose of this narrative review is to summarize the current evidence concerning the role of cholesterol efflux capacity that is important for evaluating CVD risk, focusing on pharmacological evidences and its relationship with inflammation. We conclude that HDL therapeutics are a promising area of investigation but strategies for identifying efficacy must move beyond the idea of simply raising static HDL–cholesterol levels and toward methods of measuring the dynamics of HDL particle remodeling and the generation of lipid-free apolipoprotein A-I (apoA-I). In this way, apoA-I, unlike mature HDL, can promote the greatest extent of cholesterol efflux relieving cellular cholesterol toxicity and the inflammation it causes.
Weak Polygyny in California Sea Lions and the Potential for Alternative Mating Tactics

Female aggregation and male territoriality are considered to be hallmarks of polygynous mating systems. The development of genetic parentage assignment has called into question the accuracy of behavioral traits in predicting true mating systems. In this study we use 14 microsatellite markers to explore the mating system of one of the most behaviorally polygynous species, the California sea lion (Zalophus californianus). We sampled a total of 158 female-pup pairs and 99 territorial males across two breeding rookeries (San Jorge and Los Islotes) in the Gulf of California, Mexico. Fathers could be identified for 30% of pups sampled at San Jorge across three breeding seasons and 15% of sampled pups at Los Islotes across two breeding seasons. Analysis of paternal relatedness between the pups for which no fathers were identified (sampled over four breeding seasons at San Jorge and two at Los Islotes) revealed that few pups were likely to share a father. Thirty-one percent of the sampled males on San Jorge and 15% of the sampled males on Los Islotes were assigned at least one paternity. With one exception, no male was identified as the father of more than two pups. Furthermore, at Los Islotes rookery there were significantly fewer pups assigned paternity than expected given the pool of sampled males (p<0.0001). Overall, we found considerably lower variation in male reproductive success than expected in a species that exhibits behavior associated with strongly polygynous mating. Low variation in male reproductive success may result from heightened mobility among receptive females in the Gulf of California, which reduces the ability of males to monopolize groups of females. Our results raise important questions regarding the adaptive role of territoriality and the potential for alternative mating tactics in this species.
Preferable in vitro condition for maintaining faithful DNA methylation imprinting in mouse embryonic stem cells

Epigenetic properties of cultured embryonic stem cells (ESCs), including DNA methylation imprinting, are important because they affect the developmental potential. Here, we tested a variety of culture media, including knockout serum replacement (KSR) and fetal bovine serum (FBS) with or without inhibitors of Gsk3β and Mek1/2 (2i) at various time points. In addition to the previously known passage‐dependent global changes, unexpected dynamic DNA methylation changes occurred in both maternal and paternal differentially methylated regions: under the widely used condition of KSR with 2i, a highly hypomethylated state occurred at early passages (P1–7) as well as P10, but DNA methylation increased over further passages in most conditions, except under KSR with 2i at P25. Dramatic DNA demethylation under KSR+2i until P25 was associated with upregulated Tet1 and Parp1, and their related genes, whereas 2i regulated the expressions of DNA methyltransferase‐related genes for the change in DNA methylation during the cumulative number of passages. Although DNA methylation imprinting is more labile under KSR with and without 2i, it can be more faithfully maintained under condition of cooperative FBS and 2i. Thus, our study will provide the useful information for improved epigenetic control of ESCs and iPSCs in applications in regenerative medicine.
Influence of glycemic control on some real-time biomarkers of free radical formation in type 2 diabetic patients: An EPR study.

BACKGROUND The pathology of diabetes is associated with several mechanisms, one of which is oxidative stress (OS). The relationship between OS and diabetic complications has been extensively investigated. OS has been suggested to be involved in the genesis of both macroand microangiopathy. In contrast, the relationship between OS and insulin action is a neglected research area. OBJECTIVES The aim of this study is to elucidate the effect of glycemic control in type 2 diabetic patients by following the serum levels of some real-time oxidative stress biomarkers. MATERIAL AND METHODS The study group consisted of 53 type 2 diabetic patients (31 with poor glycemic control and 22 with good glycemic control) and 24 healthy control subjects. The oxidative stress biomarkers (ROS, Asc• and •NO) were measured by using electron paramagnetic resonance spectroscopy (EPR) methods and compared with clinical parameters. RESULTS The statistically significantly higher levels of ROS products and •NO in type 2 diabetic patients in both groups compared to controls mean that the oxidation processes take place at the time the survey is performed. Free radical overproduction persists after the normalization of the glucose levels, and oxidative stress may be involved in the "metabolic memory" effect. This is confirmed by the positive correlation between ROS levels/•NO and average blood glucose levels, triglycerides, and total cholesterol. Furthermore, the low level of the ascorbate radical in both diabetes groups compared to controls confirmed an increase in oxidation processes. CONCLUSIONS Higher levels of real-time biomarkers show that intensive insulin treatment does not lead to the expected decrease in oxidative processes involving ROS and •NO, probably due to "metabolic memory".
Mechanical Assessment of Non-metallic Composite Clamps Designed for Orthopaedic Surgery

Clamps have recently gained interest due to possibility of their use in low-invasiveness operations. The work presents the mechanical tests made on connecting clamps manufactured from carbon fiber—epoxy resin composite (CF/Epoxy). The CF/Epoxy unidirectional composites were prepared with the use of different carbon fiber amount and their elasticity was analyzed. Mechanical characteristics of composite clamps was compared to typical metallic clamps. Stress relaxation tests were made on the composite clamps in simulated body fluid (SBF) at 37°C to determine their mechanical stability. It was shown that the mechanical strength of composite clamps is similar to that of metallic clamps, whereas their stiffness is comparable to bone tissue. The average variations of mechanical stability of the composite clamps kept in SBF under a constant strain were not significant at the end of 6 months aging.
Rett syndrome: a neurological disorder with metabolic components

Rett syndrome (RTT) is a neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2), a ubiquitously expressed transcriptional regulator. Despite remarkable scientific progress since its discovery, the mechanism by which MECP2 mutations cause RTT symptoms is largely unknown. Consequently, treatment options for patients are currently limited and centred on symptom relief. Thought to be an entirely neurological disorder, RTT research has focused on the role of MECP2 in the central nervous system. However, the variety of phenotypes identified in Mecp2 mutant mouse models and RTT patients implicate important roles for MeCP2 in peripheral systems. Here, we review the history of RTT, highlighting breakthroughs in the field that have led us to present day. We explore the current evidence supporting metabolic dysfunction as a component of RTT, presenting recent studies that have revealed perturbed lipid metabolism in the brain and peripheral tissues of mouse models and patients. Such findings may have an impact on the quality of life of RTT patients as both dietary and drug intervention can alter lipid metabolism. Ultimately, we conclude that a thorough knowledge of MeCP2's varied functional targets in the brain and body will be required to treat this complex syndrome.
Changes in Mycobacterium tuberculosis Genotype Families Over 20 Years in a Population-Based Study in Northern Malawi

Background Despite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection. Methods and Principal Findings In a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986–2002, and 377 spoligotypes from cultures from 347 patients from 2005–2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 (“European/American”) strains; 9% had Lineage 3 (“East-African/Indian”); 8% Lineage 1 (“Indo-Oceanic”); and 2% Lineage 2 (“East-Asian”); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed. Conclusions This is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1–3, perhaps influenced by the HIV epidemic.
Hormonal (Cortical-Gonadotropic Axis) and Physical Changes With Two Years Intense Exercise Training in Elite Young Soccer Players

Abstract Hammami, MA, Ben Abderrahman, A, Hackney, AC, Kebsi, W, Owen, AL, Nebigh, A, Racil, G, Tabka, Z, and Zouhal, H. Hormonal (cortical-gonadotropic axis) and physical changes with two years intense exercise training in elite young soccer players. J Strength Cond Res 31(9): 2388–2397, 2017—The aim of this study was to investigate the effects of 2 soccer-training seasons on physical fitness and hormone concentrations in elite youth soccer players. Twenty male elite soccer players (SP, age 14.5 ± 0.4 years) and 20 male control subjects (CS, age 14.3 ± 0.3 years) participated in the study. Anthropometric measurements, aerobic (Yo-Yo Intermittent Recovery Test Level 1 [YYIRT1]) and anaerobic soccer relevant performances (jump and sprint tests), blood testosterone (T), cortisol (C), sex hormone binding globulin (SHBG), and T/C ratio were assessed 5 times (from T0 to T4) during 2 competitive seasons. Significant differences from basal values (&Dgr;) of T, SHBG, and C between SP and CS were observed (p < 0.01). Additionally, T and T/C ratio changes were positively correlated with physical performance (p ⩽ 0.05). In conclusion, as expected, higher T concentration and greater power performance were observed in the soccer players group compared with controls. Our findings also show that the T concentrations and power performance outcomes co-vary positively over the 2 soccer seasons in soccer players.
NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer cells.

BACKGROUND & AIMS Induction of immediate early transcription factors (ITF) represents the first transcriptional program controlling mitogen-stimulated cell cycle progression in cancer. Here, we examined the transcriptional mechanisms regulating the ITF protein c-Myc and its role in pancreatic cancer growth in vitro and in vivo. METHODS Expression of ITF proteins was examined by reverse-transcription polymerase chain reaction and immunoblotting, and its implications in cell cycle progression and growth was determined by flow cytometry and [(3)H]-thymidine incorporation. Intracellular Ca(2+) concentrations, calcineurin activity, and cellular nuclear factor of activated T cells (NFAT) distribution were analyzed. Transcription factor complex formations and promoter regulation were examined by immunoprecipitations, reporter gene assays, and chromatin immunoprecipitation. Using a combination of RNA interference knockdown technology and xenograft models, we analyzed the significance for pancreatic cancer tumor growth. RESULTS Serum promotes pancreatic cancer growth through induction of the proproliferative NFAT/c-Myc axis. Mechanistically, serum increases intracellular Ca(2+) concentrations and activates the calcineurin/NFAT pathway to induce c-Myc transcription. NFAT binds to a serum responsive element within the proximal promoter, initiates p300-dependent histone acetylation, and creates a local chromatin structure permissive for the inducible recruitment of Ets-like gene (ELK)-1, a protein required for maximal activation of the c-Myc promoter. The functional significance of this novel pathway was emphasized by impaired c-Myc expression, G1 arrest, and reduced tumor growth upon NFAT depletion in vitro and in vivo. CONCLUSIONS Our study uncovers a novel mechanism regulating cell growth and identifies the NFAT/ELK complex as modulators of early stages of mitogen-stimulated proliferation in pancreatic cancer cells.
Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Abstract Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. Conclusion: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. Key Points: • Detection of single magnetically labeled MSC in-vivo using a clinical 3.0 T MRI is possible. • Fluorescent and magnetic co-labeling does not affect cell vitality. • The number of cells detected by MRI and histology has a high correlation. Citation Format: • Salamon J, Wicklein D, Didié M et al. Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice. Fortschr Röntgenstr 2014; 186: 367 – 376
Overlapping Community Detection Based on Structural Centrality in Complex Networks

Community structure is an important mesoscale topological characteristic of complex networks, which is significant for understanding structural features and organizational functions in networks. Local expansion methods have been proved to be efficient and effective for community detection. However, it has been shown that there are inherent drawbacks for these methods to uncover overlapping communities. Most methods are sensitive to initial seeds and built-in parameters, while others are inadequate to reveal the pervasive overlaps. In this paper, we propose a new local expansion method for uncovering overlapping communities based on structural centrality. The key idea of our approach is to locate structural centers of communities with the structural centrality and then expand these structural centers with a weighted strategy and a local search procedure. Experimental results both on artificial and real-world networks demonstrate that our method is effective and promising in term of finding overlapping community structures. We also show that our local expansion strategies are efficient in uncovering cohesive clusters and producing stable clustering results.
Micro-morphology of Achillea clypeolata: contribution to the pharmacognostical profile

Achillea clypeolata Sibth. & Sm. is Balkan endemic species, commonly known as yellow yarrow and traditionally used in Bulgarian folk medicine. The purpose of this study was to establish pharmacognostical profile of A. clypeolata, including macroscopic and microscopic morphological characteristics. The study also aims to propose a method for micromorphological investigation and pharmacognostical identification. As a result were established morphological characters necessary for identification of Achilleae clypeolatae flos and Achilleae clypeolatae herba – morphology of stem leaves (lanceolate in shape, pinnately lobed-margin, acute-apex with lamina), ligule petals (2.7-3 mm), involucre bracts (4.5x2 mm) and achenes (1.5-1.7 mm); micromorphology of lamina (110-130 µm), epidermal cells, stomata, glandular, non-glandular trichomes and 3-colporate, echinate pollen grains (20.5-20.8 µm). This study presents new micromorphological data. The used staining method dyed various tissues; makes visible the outlines of structures, tissues and some inclusions; allows by one procedure to visualize important diagnostic features; unlike many other methods, allowing pollen to be used as a characteristic of herbal substances. The results are useful for quality control methods for medicinal plant materials and contributes to the implementation of good practices for plant identification for the herbal industry, food, nutrient supplements and other plant based products.
Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive paralysis arising from the premature death of motor neurons. An inherited form is caused by a dominant mutation in the ubiquitously expressed superoxide dismutase (SOD1). SOD1 mutant expression within motor neurons is a determinant of onset and early disease, and mutant accumulation within microglia accelerates disease progression. Muscle also is a likely primary source for toxicity, because retraction of motor axons from synaptic connections to muscle is among the earliest presymptomatic events. To test involvement of muscle in ALS, viral delivery of transcription-mediated siRNA is shown to suppress mutant SOD1 accumulation within muscle alone but to be insufficient to maintain grip strength, whereas delivery to both motor neurons and muscle is sufficient. Use of a deletable mutant gene to diminish mutant SOD1 from muscle did not affect onset or survival. Finally, follistatin expression encoded by adeno-associated virus chronically inhibited myostatin and produced sustained increases in muscle mass, myofiber number, and fiber diameter, but these increases did not affect survival. Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression.
Water quality monitoring with internet of things (IoT)

The paper suggests an Internet of Things (IoT) based system implementation by embedding the Radio Frequency Identification (RFID) system, Wireless Sensor Network (WSN) platform and Internet Protocol (IP) based communication into a single platform for water quality monitoring (WQM) purpose. The suggested radio frequency for the proposed WSN communication to be deployed in vegetation area is 920MHz. The measured water parameter in this proposed system is pH level by using an analog pH sensor. The ambient temperature is captured during pH measurement by using an analog temperature sensor. All the WSN nodes are deployed in a real environment at the lake in the campus area of Universiti Sains Malaysia (USM) for performance evaluation. Instead of using 2.4GHz ZigBee protocol, the 920MHz Digi Mesh protocol is proposed to be implemented for water quality monitoring in vegetation area due to its ability to surpass the signal attenuation. This novel proposed system prototype was evaluated in a real environment to ensure that the main functionality on pH measuring process is following the design requirements. Several experimental analysis were conducted including the energy analysis and communication read range analysis to study the overall performance of the proposed system.