Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone inductivity comparison of control versus non-control released rhBMP2 coatings in 3D printed hydroxyapatite scaffold

Investigating the effects of rhBMP2 (recombined human bone morphogenetic protein-2) release kinetics on bone formation is important to optimize the use of rhBMP2 in tissue-engineered bone. However, there is still no direct evidence regarding how the release kinetic of rhBMP2 has effects on mesenchymal stem cells homing and differentiation during bone regeneration. In this study, we construct control and non-control released rhBMP2 coatings within the pores of 3D printed hydroxyapatite scaffold, and investigate how the release kinetic of rhBMP2 affects bone inductivity of tissue-engineered bone. We show that control released rhBMP2 has better effects on enhancing mesenchymal stem cells proliferation and migration than non-control released rhBMP2. Control released rhBMP2 promotes mesenchymal stem cells differentiation to a better extent than non-control released rhBMP2. Those findings are in consistent with the results of quantitative rhBMP2 stimulation for mesenchymal stem cells proliferation, migration and differentiation. The histological results after in vivo implantation also reveal that control released rhBMP2 coating can induce more bone formation than non-control released rhBMP2. Our data provide a basis for optimizing the rhBMP2 delivery modes in tissue-engineered bone and improving the bone inductivity of rhBMP2.
Pharmacokinetics and Efficacy of Ceftazidime-Avibactam in the Treatment of Experimental Pneumonia Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Persistently Neutropenic Rabbits

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-Kp. We investigated the pharmacokinetics and efficacy of ceftazidime-avibactam in the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits. ABSTRACT Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-Kp. We investigated the pharmacokinetics and efficacy of ceftazidime-avibactam in the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits. For single-dose and multidose (administration every 8 h) pharmacokinetics, rabbits received ceftazidime-avibactam intravenous infusions at 60/15, 90/22.5, and 120/30 mg/kg of body weight. Ceftazidime mean area under the concentration-time curves (AUCs) ranged from 287 to 608 μg·h/ml for a single dose and from 300 to 781 μg·h/ml for multiple doses. Avibactam AUCs ranged from 21 to 48 μg·h/ml for a single dose and from 26 to 48 μg·h/ml for multiple doses. KPC-Kp pneumonia was established by direct endotracheal inoculation. Treatments consisted of ceftazidime-avibactam at 120/30 mg/kg every 6 h, a polymyxin B (PMB) loading dose of 2.5 mg/kg followed by 1.5 mg/kg every 12 h q12h, or no treatment (untreated controls [UC]). There were significant reductions in the residual bacterial burden, lung weights, and pulmonary hemorrhage scores in CZA- and PMB-treated rabbits for a 7-day or a 14-day (P ≤ 0.01) course in comparison with those in the UC. These results corresponded to significant decreases in the bacterial burden in bronchoalveolar lavage fluid after a 7-day or a 14-day treatment (P ≤ 0.01). The outcomes demonstrated an improved response at 14 days versus that at 7 days. There was significantly prolonged survival in rabbits treated with CZA for 14 days in comparison with that in the PMB-treated or UC rabbits (P ≤ 0.05). This study demonstrates that ceftazidime-avibactam displays linear dose-proportional exposures simulating those seen from human plasma pharmacokinetic profiles, is active for the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits, and provides an experimental foundation for the treatment of severely immunocompromised patients with this life-threatening infection.
Identification of Echinacea Purpurea (L.) Moench Root LysM Lectin with Nephrotoxic Properties

Echinacea purpurea (L.) Moench (EP) is a well-studied plant used for health benefits. Even though there are a lot of data on EP secondary metabolites, its active proteins are not studied well enough. The aim of our experiment was to purify lectin fraction from EP roots and evaluate its biological activity in vitro as well as its effect on kidney morphology in vivo. An EP root glycoprotein fraction was purified by affinity chromatography, identified by LC-MS/MS, and used for biological activity tests in vitro and in vivo. Identified glycoproteins were homologous with the LysM domain containing lectins from the Asteraceae plants Helianthus annuus L. , Lactuca sativa L. , Cynara cardunculus L. A purified fraction was tested by hemagglutination and hemagglutination inhibition (by carbohydrate reactions) in vitro. We purified the hemagglutinating active ~40 kDa size lactose, D-mannose, and D-galactose specific glycoproteins with two peptidoglycan binding LysM (lysine motif) domains. Purified LysM lectin was tested in vivo. Eight-week old Balb/C male mice (n = 15) were treated with 5 μg of the purified lectin. Injections were repeated four times per week. At the fifth experimental week, animals were sedated with carbon dioxide, then euthanized by cervical dislocation and their kidney samples were collected. Morphological changes were evaluated in hematoxylin and eosin stained kidney samples. The purified LysM lectin induced a statistically significant (p < 0.05) kidney glomerular vacuolization and kidney tubular necrosis (p < 0.001).
Detection of Inflicted Bruises by Alternate Light: Results of a Randomized Controlled Trial†, ‡, §

Bruises are often difficult to detect on victims of violence, potentially impacting investigation and prosecution. The purpose of our randomized controlled trial was to measure the effectiveness of an alternate light source (ALS) within visible and long ultraviolet spectrums at improving bruise detection compared to white light over time. We also examined the effects of skin color, age, gender, localized fat, and injury mechanism on bruise detection. Participants included 157 healthy adults with balanced sampling across six skin color categories. Bruises were created under the controlled application of a paintball pellet and dropped weight to one upper and lower arm, respectively. Using a crossover design, both bruises were examined 21 times over 4 weeks. Ten different wavelength (350–535 nm) and filter (yellow, orange, red) combinations were used. Multilevel models were used to analyze 2903 examinations on both upper and lower arms. Results in multivariable models showed after controlling for other covariates 415 and 450 nm using a yellow filter had greater odds of detecting evidence of bruising than white light (Upper Arm: 415 nm: OR = 5.34, 95% CI: 4.35–6.56; 450 nm: OR = 4.08, 95% CI: 3.36–4.96). Under either light source, being female and having more localized fat had increased odds of detecting bruises created by the dropped weight (female: OR = 2.96, 95% CI: 2.37–3.70; fat: OR = 1.21, 95% CI: 1.09–1.34). Our results support ALS as an appropriate tool to enhance concurrent physical assessment of bruises in the presence of known history of injury. Future development and evaluation of clinical practice guidelines for ALS application are needed.
Control of DNA Damage Bypass by Ubiquitylation of PCNA

DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.
Antioxidant potential of biflavonoid attenuates hyperglycemia by modulating the carbohydrate metabolic enzymes in high fat diet/streptozotocin induced diabetic rats

ABSTRACT Objectives: The present study was to isolate the biflavonoid (a bimolecular kaemferol structured molecule) and test its efficacy on oxidative stress and carbohydrate metabolic key enzymes in control and high fat diet and streptozotocin -induced diabetic rats. Methods: Type 2 diabetes was induced in male albino wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, cholesterol 0.2%, and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). Results: At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. Discussion: Oral administration of biflavonoid to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The effect produced by the biflavonoid on various parameters was comparable to that of metformin.
Bee Products in Dermatology and Skin Care

Honey, propolis, bee pollen, bee bread, royal jelly, beeswax and bee venom are natural products which have been used in medicine since ancient times. Nowadays, studies indicate that natural bee products can be used for skin treatment and care. Biological properties of these products are related to flavonoids they contain like: chrysin, apigenin, kaempferol, quercetin, galangin, pinocembrin or naringenin. Several pharmacological activities of phenolic acids and flavonoids, and also 10-hydroxy-trans-2-decenoic acid, which is present in royal jelly, have been reported. Royal jelly has multitude of pharmacological activities: antibiotic, antiinflammatory, antiallergenic, tonic and antiaging. Honey, propolis and pollen are used to heal burn wounds, and they possess numerous functional properties such as: antibacterial, anti-inflammatory, antioxidant, disinfectant, antifungal and antiviral. Beeswax is used for production of cosmetics and ointments in pharmacy. Due to a large number of biological activities, bee products could be considered as important ingredients in medicines and cosmetics applied to skin.
Cannabis Sativa Revisited—Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and Endocannabinoid Response System in Critically Ill Patients with Sepsis

Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
Isolation and Characterization of Antifungal Metabolites from the Melia azedarach-Associated Fungus Diaporthe eucalyptorum.

Two biosynthetically related new metabolites, eucalyptin A (1) and eucalyptin B (2), along with six known compounds (3-8), eugenitol (3), cytosporone C (4), 4-hydroxyphenethyl alcohol (5), 1-(4-hydroxyphenyl)ethane-1,2-diol (6), N-(2-hydroxy-2-phenylethyl)acetamide (7) and phomopene (8), were isolated from the solid rice cultures of the endophytic fungus Diaporthe eucalyptorum KY-9, associated with Melia azedarach. In addition, two further new derivatives (2a, 2b) were prepared from 2. Their structures were elucidated by exhaustive analysis of NMR and ESIMS data, and chemical transformations. Compound (1) was identified as a rare polyketide fatty acid, (8E)-3,5,11-trihydroxy-2,10,12-trimethyltetradecenoic acid, and 2 is the first cyclic depsipeptide containing the same fatty acid residue as 1. The compound 2 are a member of the cyclic depsipeptides family and are based on a tripeptide chain composed by Gly-Gly-Thr. Its N-terminal end is N-acylated by an 11-hydroxy fatty acid with branch alkyl chain of 14:1. The 11-hydroxyl group closes a 22-membered lactone ring with the carboxylic group of the C-terminal amino acid. The isolated compounds were tested for their inhibitory activity against the four plant pathogenic fungi Alternaria solani, Botrytis cinerea, Fusarium solani, and Gibberella saubinettii. Compounds 1, 4, 6, and 7 exhibited antifungal activities against the pathogens, Alternaria solani with minimal inhibitory concentration (MIC) values from 6.25 to 50 μM. Thus, strain KY-9 represents an untapped source for the development of biological control agents to prevent the infection of pathogenic fungus A. solani.
Optimization of Chitosan–Alginate Microparticles for Delivery of Mangostins to the Colon Area Using Box–Behnken Experimental Design

Chitosan-alginate microparticles loaded with hydrophobic mangostins present in the mangosteen rind extract have been formulated and optimized for colon-targeted bioactive drug delivery systems. The chitosan–mangostin microparticles were prepared using the ionotropic gelation method with sodium tripolyphosphate as the cross-linking agent of chitosan. The chitosan–mangostin microparticles were then encapsulated in alginate with calcium chloride as the linking agent. The mangostin release profile was optimized using the Box–Behnken design for response surface methodology with three independent variables: (A) chitosan–mangostin microparticle size, (B) alginate:chitosan mass ratio, and (C) concentration of calcium chloride. The following representative equation was obtained: percent cumulative release of mangostins (10 h) = 59.51 − 5.16A + 20.00B − 1.27C − 1.70AB − 5.43AC − 5.04BC + 0.0579A2 + 10.25B2 + 1.10C2. Cumulative release of 97% was obtained under the following optimum condition for microparticle preparation: chitosan–mangosteen particle size < 100 µm, alginate:chitosan mass ratio of 0.5, and calcium chloride concentration of 4% w/v. The alginate to chitosan mass ratio is the statistically significant variable in the optimization of sequential release profile of mangostins in simulated gastrointestinal fluids. Furthermore, a sufficient amount of alginate is necessary to modify the chitosan microparticles and to achieve a complete release of mangostins. The results of this work indicate that the complete release of mangostins to the colon area can be achieved using the chitosan–alginate microparticles as the bioactive delivery system.
Validation of Patient‐Reported Outcomes Information System Sleep Disturbance and Sleep‐Related Impairment in adults with atopic dermatitis *

Sleep disturbances are common in adults with atopic dermatitis (AD). Patient‐Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep‐Related Impairment (SRI) are validated questionnaires to assess sleep in adults. Little is known about their measurement properties in adults with AD.
Dynamics of transmissible gastroenteritis virus internalization unraveled by single‐virus tracking in live cells

Transmissible gastroenteritis virus (TGEV) is a swine enteropathogenic coronavirus that causes significant economic losses in swine industry. Current studies on TGEV internalization mainly focus on viral receptors, but the internalization mechanism is still unclear. In this study, we used single‐virus tracking to obtain the detailed insights into the dynamic events of the TGEV internalization and depict the whole sequential process. We observed that TGEVs could be internalized through clathrin‐ and caveolae‐mediated endocytosis, and the internalization of TGEVs was almost completed within ~2 minutes after TGEVs attached to the cell membrane. Furthermore, the interactions of TGEVs with actin and dynamin 2 in real time during the TGEV internalization were visualized. To our knowledge, this is the first report that single‐virus tracking technique is used to visualize the entire dynamic process of the TGEV internalization: before the TGEV internalization, with the assistance of actin, clathrin, and caveolin 1 would gather around the virus to form the vesicle containing the TGEV, and after ~60 seconds, dynamin 2 would be recruited to promote membrane fission. These results demonstrate that TGEVs enter ST cells via clathrin‐ and caveolae‐mediated endocytic, actin‐dependent, and dynamin 2‐dependent pathways.
Automatic Detection of Simulated Motion Blur in Mammograms.

PURPOSE To use machine-learning algorithms and blur measure (BM) operators to automatically detect motion blur in mammograms. Motion blur has been reported to reduce lesion detection performance and mask small abnormalities, resulting in failure to detect them until they reach more advanced stages. Automatic detection of blur could support the clinical decision-making process during the mammography exam by allowing for an immediate retake, thereby preventing unnecessary expense, time, and patient anxiety. METHODS Blur was simulated mathematically to mimic the real blur seen in clinical practice. The blur point-spread-function (PSF) mask is generated by distributing pixel intensity of an image pixel moving under random motion within the range of blur effect (the maximum amount of tissue motion allowed). The random motion trajectory vector is generated on a super-sampled image frame to accommodate smaller substeps; the vector was then sampled on a regular pixel grid using subpixel linear interpolation to generate the blur PSF mask. This randomly-generated motion trajectory is constrained by several factors: the effects of variations in tissue elasticity, imaging exposure time, and size of blur effect (motion boundary in millimeters) were examined. The blur mask is convolved with a mammogram to create blur. Five motion blur magnitudes (0.1, 0.25, 0.5, 1.0, and 1.5 mm) were simulated on 244 and 434 mammograms from the INbreast and DDSM databases, respectively. Blur was quantified using nine BM operators for each mammogram and at each blur level. The mammograms were assigned to training (70%) and testing (30%) datasets to train three machine-learning classifiers: Ensemble Bagged Trees, fine Gaussian SVM, and weighted KNN, to distinguish five levels of blurred from unblurred mammograms, using six-way classification. RESULTS For the INbreast mammograms, the average classification accuracies were 87.7%, 85.7%, and 85.7% for Ensemble Bagged Trees, fine Gaussian SVM, and weighted KNN, respectively, and the average classification accuracies for DDSM were 93.5%, 93.6%, and 92.7% for Ensemble Bagged Trees, fine Gaussian SVM, and weighted KNN, respectively. CONCLUSIONS Preliminary results show the potential to detect simulated blur automatically using those methods. Although limited work has been done to quantify the effects of motion blur on radiologists' performance, there is evidence that motion blur might not be detected visually by a human observer and could negatively affect radiologists' lesion detection performance. As of this date, no other study has investigated the ability of machine-learning classifiers and BM operators to detect motion blur in mammograms.
Stunned and Hibernating Myocardium: Where Are We Nearly 4 Decades Later?

T he concepts of stunned and hibernating myocardium were described and received considerable attention in the 1980s. These phenomena, related to myocardial ischemia (Figure 1), occur far more frequently than when they were initially described. This article defines these conditions, summarizes what has been learned about them since their original descriptions, and shows current importance of their understanding.
The benefits of physical exercise for the health of the pancreatic β‐cell: a review of the evidence

What is the topic of this review? This review discusses the evidence of the benefits of exercise training for β‐cell health through improvements in function, proliferation and survival which may have implications in the treatment of diabetes. What advances does it highlight? This review highlights how exercise may modulate β‐cell health in the context of diabetes and highlights the need for further exploration of whether β‐cell preserving effects of exercise translates to T1D.
Role of the ESCRT‐III complex in controlling integrity of the Salmonella‐containing vacuole

Intracellular pathogens need to establish specialised niches for survival and proliferation in host cells. The enteropathogen Salmonella enterica accomplishes this by extensive reorganisation of the host endosomal system deploying the SPI2‐encoded type III secretion system (SPI2‐T3SS). Fusion events of endosomal compartments with the Salmonella‐containing vacuole (SCV) form elaborate membrane networks within host cells enabling intracellular nutrition. However, which host compartments exactly are involved in this process and how the integrity of Salmonella‐modified membranes is accomplished are not fully resolved. An RNA interference knockdown screen of host factors involved in cellular logistics identified the ESCRT (endosomal sorting complex required for transport) system as important for proper formation and integrity of the SCV in infected epithelial cells. We demonstrate that subunits of the ESCRT‐III complex are specifically recruited to the SCV and membrane network. To investigate the role of ESCRT‐III for the intracellular lifestyle of Salmonella, a CHMP3 knockout cell line was generated. Infected CHMP3 knockout cells formed amorphous, bulky SCV. Salmonella within these amorphous SCV were in contact with host cell cytosol, and the attenuation of an SPI2‐T3SS‐deficient mutant strain was partially abrogated. ESCRT‐dependent endolysosomal repair mechanisms have recently been described for other intracellular pathogens, and we hypothesise that minor damages of the SCV during bacterial proliferation are repaired by the action of ESCRT‐III recruitment in Salmonella‐infected host cells.