Miracle-dz/UniFAR-FTUs huggingface dataset:
AIE-active fluorescent polymeric nanoparticles about dextran derivative: preparation and bioimaging application

Abstract Aggregation-induced emission (AIE), as a special phenomenon of fluorescence, can elegantly overcome the fluorescence quenching caused by common fluorescent materials under high concentration conditions and has attracted interest of researchers in many fields. Particularly AIE-active polymer nanoparticles have been widely utilized in a modern biomedical research. In this work, we prepared a novel kind of AIE-active fluorescent polymeric nanoparticals (Dex-OH-CHO) through a facile esterification between a new hydrophobic AIE-active 1, 8-naphthalimide derivative and the hydrophilic dextran. The structure and optical properties of Dex-OH-CHO were characterized in detail by FTIR, 1H NMR, XPS, TEM and fluorescence spectra. The results showed that Dex-OH-CHO emitted light-blue fluorescence in aqueous solution with high fluorescent quantum yield (Φ = 24.43%, concentration is 20 μg/mL), low CMC (5 μg/mL), good photostability, high water solubility and well dispersivity. Moreover, good biocompatibility and ideal cell uptake made Dex-OH-CHO had a great application potential in biological imaging.
Doxorubicin‐induces NFAT/Fas/FasL cardiac apoptosis in rats through activation of calcineurin and P38 MAPK and inhibition of mTOR signalling pathways

This study investigated the role of NFAT/Fas/FasL axis in cardiomyocyte apoptosis following doxorubicin (DOX) treatment in rats and evaluated the involvement and regulation of all NFAT members in cardiac apoptosis. Forty adult male Wistar rats were divided equally into control or DOX‐treated groups (15 mg/kg over 2 weeks). Cardiomyocytes were cultured and pre‐incubated with various inhibitors and activators (10 μmol/L) prior to DOX exposure (1 μmol/L). In the left ventricles and cultured cells, DOX increased cytoplasmic protein levels of cytochrome C, Bax and increased the activities of caspase‐8, caspase3, ERK1/2, JNK, and P38 mitogen‐activated protein kinases (MAPKs), reducing levels of Bcl‐2 and the activity of mTOR, and inducing cell death. In addition, DOX enhanced mRNA and protein levels of Fas and FasL. Furthermore, the nuclear and cytoplasmic levels of NFAT1 and nuclear accumulation of NFAT2‐4were increased with DOX treatment. The inhibition of calcineurin with FK506 significantly inhibited the nuclear levels of NFAT2 and NFAT4 and the inhibition of P38 MAPK with SB203580 inhibited the nuclear and cytoplasmic accumulation of NFAT1. However, the activation of mTOR by IGF‐1 significantly lowered NFAT3. In conclusion, NFAT/Fas/FasL‐induced cell death in cardiac myocytes of DOX‐treated rats is regulated, at least, by the activation of calcineurin and P38 MAPK and inhibition of mTOR.
Cross-kingdom mimicry of the receptor signaling and leukocyte recruitment activity of a human cytokine by its plant orthologs

Human macrophage migration-inhibitory factor (MIF) is an evolutionarily-conserved protein that has both extracellular immune-modulating and intracellular cell-regulatory functions. MIF plays a role in various diseases, including inflammatory diseases, atherosclerosis, autoimmunity, and cancer. It serves as an inflammatory cytokine and chemokine, but also exhibits enzymatic activity. Secreted MIF binds to cell-surface immune receptors such as CD74 and CXCR4. Plants possess MIF orthologs but lack the associated receptors, suggesting functional diversification across kingdoms. Here, we characterized three MIF orthologs (termed MIF/d-dopachrome tautomerase–like proteins or MDLs) of the model plant Arabidopsis thaliana. Recombinant Arabidopsis MDLs (AtMDLs) share similar secondary structure characteristics with human MIF, yet only have minimal residual tautomerase activity using either p-hydroxyphenylpyruvate or dopachrome methyl ester as substrate. Site-specific mutagenesis suggests that this is due to a distinct amino acid difference at the catalytic cavity-defining residue Asn-98. Surprisingly, AtMDLs bind to the human MIF receptors CD74 and CXCR4. Moreover, they activate CXCR4-dependent signaling in a receptor-specific yeast reporter system and in CXCR4-expressing human HEK293 transfectants. Notably, plant MDLs exert dose-dependent chemotactic activity toward human monocytes and T cells. A small molecule MIF inhibitor and an allosteric CXCR4 inhibitor counteract this function, revealing its specificity. Our results indicate cross-kingdom conservation of the receptor signaling and leukocyte recruitment capacities of human MIF by its plant orthologs. This may point toward a previously unrecognized interplay between plant proteins and the human innate immune system.
Detection and Transstadial Passage of Babesia Species and Borrelia burgdorferi Sensu Lato in Ticks Collected from Avian and Mammalian Hosts in Canada

Lyme disease and human babesiosis are the most common tick-borne zoonoses in the Temperate Zone of North America. The number of infected patients has continued to rise globally, and these zoonoses pose a major healthcare threat. This tick-host-pathogen study was conducted to test for infectious microbes associated with Lyme disease and human babesiosis in Canada. Using the flagellin (flaB) gene, three members of the Borrelia burgdorferi sensu lato (Bbsl) complex were detected, namely a Borrelia lanei-like spirochete, Borrelia burgdorferi sensu stricto (Bbss), and a distinct strain that may represent a separate Bbsl genospecies. This novel Bbsl strain was detected in a mouse tick, Ixodes muris, collected from a House Wren, Troglodytes aedon, in Quebec during the southward fall migration. The presence of Bbsl in bird-feeding larvae of I. muris suggests reservoir competency in three passerines (i.e., Common Yellowthroat, House Wren, Magnolia Warbler). Based on the 18S ribosomal RNA (rRNA) gene, three Babesia species (i.e., Babesia divergens-like, Babesia microti, Babesia odocoilei) were detected in field-collected ticks. Not only was B. odocoilei found in songbird-derived ticks, this piroplasm was apparent in adult questing blacklegged ticks, Ixodes scapularis, in southern Canada. By allowing live, engorged ticks to molt, we confirm the transstadial passage of Bbsl in I. muris and B. odocoilei in I. scapularis. Bbss and Babesia microti were detected concurrently in a groundhog tick, Ixodes cookei, in Western Ontario. In Alberta, a winter tick, Dermacentor albipictus, which was collected from a moose, Alces alces, tested positive for Bbss. Notably, a B. divergens-like piroplasm was detected in a rabbit tick, Haemaphysalis leporispalustris, collected from an eastern cottontail in southern Manitoba; this Babesia species is a first-time discovery in Canada. This rabbit tick was also co-infected with Borrelia lanei-like spirochetes, which constitutes a first in Canada. Overall, five ticks were concurrently infected with Babesia and Bbsl pathogens and, after the molt, could potentially co-infect humans. Notably, we provide the first authentic report of I. scapularis ticks co-infected with Bbsl and B. odocoilei in Canada. The full extent of infectious microorganisms transmitted to humans by ticks is not fully elucidated, and clinicians need to be aware of the complexity of these tick-transmitted enzootic agents on human health. Diagnosis and treatment must be administered by those with accredited medical training in tick-borne zoonosis.
Fast dissolving glucose porogens for early calcium phosphate cement degradation and bone regeneration

Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100–150 μm (GMP-S) and 150–300 μm (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.
The Use of Anterograde Percutaneous Transluminal Coronary Angioplasty Balloons in Congenital Nasolacrimal Duct Obstruction: A Cost-Effective Alternative to the Traditional Dacryoplasty Balloons

Purpose: To assess the efficacy of commonly available coronary angioplasty balloon catheters as a low-cost alternative to the traditional dacryoplasty catheters in select patients of congenital nasolacrimal duct obstruction. Methods: A prospective, interventional study was performed between July 2018 and December 2018 in children with congenital nasolacrimal duct obstruction, who underwent balloon dacryoplasty using the coronary angioplasty balloon catheters (2.75 × 10 mm, SPALNO, Cardiomac, Haryana, India). The inclusion criteria were children ≥4 years of age, and/or previously failed probing and/or previous failed intubation. Parameters documented were demographics, techniques, costs, complications, and postoperative outcomes. Results: Twenty-three eyes of 22 children underwent balloon dacryoplasty using coronary angioplasty balloon catheters. The mean age of the patients was 4.33 years (range 1.5–10 years). The procedure was performed in 8 patients (8 eyes, 35%) as the primary procedure. The remaining 14 patients (15 eyes, 65%) had a history of probing, of which 4 eyes had it twice earlier. All eyes underwent balloon dacryoplasty as per standard protocols. The insertion profile and trackability of the coronary catheters were good. At a mean follow up of 6.17 months (range 1.5–9 months), anatomical and functional success was obtained in 87% cases (n = 20/23). No lacrimal passage trauma or injuries were noted during the procedure. The cost of coronary balloon catheter was approximately $60. Conclusions: The present pilot study has shown that outcomes of balloon dacryoplasty in patients with congenital nasolacrimal duct obstruction with coronary balloon catheters is comparable to that of traditional balloons and offers significant economic advantage for developing nations. Balloon dacryoplasty in patients with congenital nasolacrimal duct obstruction with the use of coronary balloon catheters has comparable outcomes to that of traditional balloons and offers significant economic advantage for developing nations.
Co-administration of vaccines: a focus on tetravalent Measles-Mumps-Rubella-Varicella (MMRV) and meningococcal C conjugate vaccines

ABSTRACT Simultaneous administration of different vaccines is a strategy to increase the possibility to receive vaccines at appropriate age, safely and effectively, reducing the number of sessions and allowing a more acceptable integration of new vaccines into National Immunization Programs (NIPs). Co-administration can be performed when there are specific indications in the Summary of Product Characteristics (SmPC) of the vaccines; but, in absence of these indications, the practice is possible if there are no specific contraindications nor scientific evidence to discourage simultaneous administration. The aim of this work is to review the safety and efficacy of co-administration of the tetravalent measles, mumps, rubella, and varicella (MMRV) and the meningococcal C (Men C) conjugate vaccines after 12 months of age. Several studies demonstrated that MMRV and Men C conjugate vaccines can be administered concomitantly without a negative impact on the safety and immunogenicity of either vaccines, inducing highly immunogenic responses.
The Impact of Wealth Status on Food Intake Patterns in Filipino School-Aged Children and Adolescents

Socio-economic status (SES) has an impact on food consumption in developing countries. However, the impact of SES on dietary patterns in Filipino school-aged children is currently unknown. The aim of this study was to fill this knowledge gap, using data from the 2013 National Nutrition Survey. Dietary intake of 11,691 children (6–18 years) were assessed using a 24-h recall. All food and beverages were assigned to one of 85 food groups. Mean daily intake, percent consuming (prevalence), and contribution to energy intake were determined, and stratified by SES, in 6–9 years old, 10–12 years old, and 13–18 years old. Rice was the most consumed food and the primary source of energy across all three age groups, independent of SES. Children of poor SES presented greater consumption of fish, vegetables, fruit, and table sugar (p < 0.05). In comparison, children of rich and middle SES presented greater consumption of milk, chicken, pork, sausages, and soft-drinks (p < 0.05). In conclusion, SES impacts the type of foods consumed by Filipino children, with children in the poorest households being most at risk of consuming low-variety diets. This analysis could be used to support public health strategies to improve dietary diversity, and potentially nutrient intake, in Filipino children.
Potential roles in cardiac physiology and pathology of the cation channel TRPV2 expressed in cardiac cells and cardiac macrophages: a mini-review.

TRPV2 is a well-conserved channel protein expressed in almost all tissues. Cardiomyocyte TRPV2 is expressed in the intercalated discs of the cardiac sarcomeres where it is involved in maintaining the proper mechanoelectric coupling and structure. It is also abundantly expressed in the intracellular pools, mainly the endoplasmic reticulum. Under pathological conditions, TRPV2 is translocated to the sarcolemma where it mediates an abnormal [Ca]2+ entry that may contribute to disease progression. In addition, an intracellularly diffused TRPV2 expression is present in resident cardiac macrophages. Upon infection or inflammation, TRPV2 is engaged in early phagosomes and is, therefore, potentially involved in protecting the cardiac tissue. Following acute myocardial infarction, a profound elevated expression of TRPV2 is observed on the cell membrane of the peri-infarct macrophages. The macrophage TRPV2 may harbor a detrimental effect in cardiac recovery by increasing unfavorable migration and phagocytosis processes in the injured heart. Most reports suggest that while cardiac TRPV2 activation may be beneficial under specific physiological conditions, both cardiac- and macrophage-related TRPV2 blocking can significantly ameliorate disease progression in various pathological states. To verify this possibility, the time frame of TRPV2 overexpression and its mediated signaling need to be fully characterized in both cardiomyocyte and cardiac macrophage populations.
Effectiveness of Individual Nutrition Education Compared to Group Education, in Improving Anthropometric and Biochemical Indices among Hypertensive Adults with Excessive Body Weight: A Randomized Controlled Trial

Objective: The study aims to compare the effectiveness of individual and group nutrition education methods in improving key anthropometric and biochemical markers in drug-treated, overweight-obese hypertensive adults. Methods: The randomized trial included 170 patients with pharmacologically well-controlled primary hypertension and body mass index (BMI) ≥ 25 kg/m2. For six months, the patients received six sessions, either one-to-one individual nutrition education (IE, n = 89) or group education (GE, n = 81), developed by dietitians. Anthropometric measurements, body composition, and fasting measures of biochemical parameters were obtained at baseline and after six months of intervention. Results: 150 patients completed the nutrition education program. The IE group significantly improved in many parameters compared to the GE group, including weight (p < 0.001), waist circumference (p < 0.001), BMI (p < 0.001), systolic and diastolic blood pressure (BP) (p < 0.001), fasting plasma glucose (p = 0.011), oral glucose tolerance test (OGGT) (p = 0.030), and insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) (p < 0.001). The groups did not differ in terms of total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations. Conclusion: Individual nutrition education is more effective than group education in terms of improving anthropometric and biochemical indices in overweight-obese hypertensive adults.
Is the low AMH level associated with the risk of cardiovascular disease in obese pregnants?

Abstract Our aim was to investigate whether Antimullerian Hormone (AMH), complete blood count (CBC), Homeostasis model assessment (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight gain have any diagnostic value for the prediction of cardiovascular disease (CVD) in obese and non-obese pregnant patients. A prospective, case-control study was carried out, including 187 patients (93 obese, and 94 non-obese). CVD risk for each patient was evaluated according to the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA). A multivariate logistic regression model was used to identify the independent risk factors of CVD in obese and non-obese patients. The obese patients had significantly lower levels of AMH when compared to the non-obese ones (p = .002). Insulin, HOMA-IR, HbA1c, and SBP were significantly higher in obese patients than non-obese ones (p < .001, p < .001 and p = .001, respectively). Age, SBP, and decreased AMH levels had significantly associated with risk factors of CVD in the obese group (p = .001, p = .002, and p = .049, respectively). Our study suggests that decreased AMH levels, increased age, and SBP are associated with CVD in obese patients. AMH may be used to evaluate CVD risk in advanced aged, obese patients. IMPACT STATEMENT What is already known on this subject? Obesity is one of the most common medical complications of pregnancy. Obesity increases maternal complications such as preeclampsia, caesarean rate, cardiovascular disease, obesity, and diabetes after pregnancy; and neonatal complications including macrosomia, hypoglycaemia, hyperbilirubinemia, delivery trauma, shoulder dystocia, and adult-onset obesity, and diabetes. Obese patients have lower serum AMH levels. What the results of this study add? A significant relationship between AMH levels and CVD risk in obese pregnant women was observed. What are the implications of these findings for clinical practice and/or further research? Based on this finding, we concluded that decreased AMH levels are predictive for CVD in obese pregnant women.
Activity of dual PI3K/mTOR inhibitor, NVP-BEZ235, and mTOR inhibitor, RAD001 (everolimus), in endometrial cancer cell lines.

5074 Background: PI3K and its downstream mTOR play a critical role in malignant phenotype in many tumors. PI3K pathway is frequently hyper-activated in endometrial cancer through various PI3K/AKT activating mutations (such as PTEN and PIK3CA). As these mutations activate not only mTOR pathway but other AKT effector pathways, dual inhibition of PI3K and mTOR might be more effective than mTOR inhibition alone in endometrial cancer. NVP-BEZ235 is a dual inhibitor of PI3K and mTOR, and is currently under phase I/II trials in solid tumors. Our aims were to compare the activity of NVP-BEZ235 with that of mTOR inhibitor, RAD001, in endometrial cancer cell lines. Methods: Using 13 endometrial cancer cell lines, 11 of which possess mutations in PTEN and/or PIK3CA, we evaluated the effects of NVP-BEZ235 and RAD001 on cell growth by MTT assay and FACS analysis. A xenograft endometrial cancer model was used to determine in vivo effects. Results: RAD001 at 50nM showed growth inhibitory effect with 30%-60% reduction ag.
Inhibition of MDR1 Overcomes Resistance to Brentuximab Vedotin in Hodgkin Lymphoma

Purpose: In classical Hodgkin lymphoma, the malignant Reed–Sternberg cells express the cell surface marker CD30. Brentuximab vedotin is an antibody–drug conjugate (ADC) that selectively delivers a potent cytotoxic agent, monomethyl auristatin E (MMAE), to CD30-positive cells. Although brentuximab vedotin elicits a high response rate (75%) in relapsed/refractory Hodgkin lymphoma, most patients who respond to brentuximab vedotin eventually develop resistance. Patients and Methods: We developed two brentuximab vedotin–resistant Hodgkin lymphoma cell line models using a pulsatile approach and observed that resistance to brentuximab vedotin is associated with an upregulation of multidrug resistance-1 (MDR1). We then conducted a phase I trial combining brentuximab vedotin and cyclosporine A (CsA) in patients with relapsed/refractory Hodgkin lymphoma. Results: Here, we show that competitive inhibition of MDR1 restored sensitivity to brentuximab vedotin in our brentuximab vedotin–resistant cell lines by increasing intracellular MMAE levels, and potentiated brentuximab vedotin activity in brentuximab vedotin–resistant Hodgkin lymphoma tumors in a human xenograft mouse model. In our phase I trial, the combination of brentuximab vedotin and CsA was tolerable and produced an overall and complete response rate of 75% and 42% in a population of patients who were nearly all refractory to brentuximab vedotin. Conclusions: This study may provide a new therapeutic strategy to combat brentuximab vedotin resistance in Hodgkin lymphoma. This is the first study reporting an effect of multidrug resistance modulation on the therapeutic activity of an ADC in humans. The expansion phase of the trial is ongoing and enrolling patients who are refractory to brentuximab vedotin to confirm clinical activity in this population with unmet need.