Miracle-dz/UniFAR-FTUs huggingface dataset:
Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.
Pathogenesis and Clinical Management of Uterine Serous Carcinoma

Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer that has not been well characterized. It accounts for less than 10% of all endometrial cancers and 80% of endometrial cancer–related deaths. Currently, staging surgery together with chemotherapy or radiotherapy, especially vaginal cuff brachytherapy, is the main treatment strategy for USC. Whole-exome sequencing combined with preclinical and clinical studies are verifying a series of effective and clinically accessible inhibitors targeting frequently altered genes, such as HER2 and PI3K3CA, in varying USC patient populations. Some progress has also been made in the immunotherapy field. The PD-1/PD-L1 pathway has been found to be activated in many USC patients, and clinical trials of PD-1 inhibitors in USC are underway. This review updates the progress of research regarding the molecular pathogenesis and putative clinical management of USC.
Flow-Based Dynamic Approach to Assess Bioaccessible Zinc in Dry Dog Food Samples

This work proposes a simple and easy-to-use flow-through system for the implementation of dynamic extractions, aiming at the evaluation of bioaccessible zinc and the characterization of leaching kinetics in dry dog food samples. The kinetic profile of Zn extraction was determined by flame atomic absorption spectroscopy and the results were fitted in an exponential function (R2 > 0.960) compatible with a two first-order reactions model. Values of fast leachable Zn ranged from 83 ± 1 to 313 ± 5 mg of Zn per kg of sample, with associated rate constants ranging from 0.162 ± 0.004 to 0.290 ± 0.014 min−1. Similar results were observed compared to the static batch extraction. The percentage of bioaccessible Zn ranged from 49.0 to 70.0%, with an average value of 58.2% in relation to total Zn content. Principal component analysis regarding the variables fast leachable Zn, associated rate constant, total Zn, and market segment, has shown that 84.6% of variance is explained by two components, where the second component (24.0%) presented loadings only for the fast leachable Zn and associated rate constant. The proposed method is suitable for the fast evaluation (<1 h) of leaching kinetics and bioaccessibility in dry dog food.
Effects of sweet orange aromatherapy on pain and anxiety during needle insertion among patients undergoing hemodialysis: A quasi-experimental study.

PURPOSE Patients undergoing hemodialysis experience pain and anxiety during needle insertion, and the scientific interest in aromatherapy in reducing pain and anxiety is increasing. Thus, this study aimed to determine the effects of sweet orange aromatherapy on pain and anxiety during needle insertion in hemodialysis. DESIGN Quasi-experimental, pretest, and posttest. METHODS This study was carried out among 50 patients with chronic kidney disease who were non-randomly assigned to either sweet orange aromatherapy or calm breathing in three outpatient hemodialysis centers in the Philippines between July and August 2015. The numeric rating scale and adapted state-trait anxiety inventory were utilized to measure pain and anxiety. RESULTS After the intervention, both the pain and anxiety scores were significantly lower for patients who received sweet orange aromatherapy than those who received calm breathing. The results obtained modest effect sizes that imply high practical significance. CONCLUSION The sweet orange aromatherapy can be effective in reducing pain and anxiety. Thus, this can be used by nurses as an alternative and complementary approach to reduce both pain and anxiety in painful procedures like needle insertion.
Later-Life Exposure to Moderate PM2.5 Air Pollution and Life Loss of Older Adults in Taiwan

Background: Few studies have directly estimated expected life loss attributable to lifetime exposure to fine particulate matter (PM2.5). Methods: We used claims data from Taiwan’s National Health Insurance to create 63 study cohorts of 1.91 million residents aged 60–79 years old residing in small areas where air quality monitoring stations are situated. The survival status of each person was followed from 2001 to 2016. We applied an extrapolation algorithm to estimate the lifetime survival function so that we could directly estimate life expectancy (LE) and the lifetime exposure to PM2.5 of each cohort. We estimated the association between LE and lifetime exposure to PM2.5 among the 63 cohorts. We also fit a Cox proportional hazards model to all the data combined to estimate the relative risk of mortality. Results: Older adults who lived in an area with a higher lifetime weighted average PM2.5 of 10 μg/m3 had a shortened LE by 0.34 (95% CI: 0.22–0.46) years. The hazard ratio of mortality was 1.0245 (1.0242–1.0248) per one μg/m3 increase in lifetime average PM2.5. Conclusion: This study provides strong evidence that later-life exposure to moderate PM2.5 air pollution had a substantial impact on the life loss of older adults.
Surface Energy of Au Nanoparticles Depending on Their Size and Shape

Motivated by often contradictory literature reports on the dependence of the surface energy of gold nanoparticles on the variety of its size and shape, we performed an atomistic study combining molecular mechanics and ab initio calculations. We show that, in the case of Au nanocubes, their surface energy converges to the value for (001) facets of bulk crystals. A fast convergence to a single valued surface energy is predicted also for nanospheres. However, the value of the surface energy is larger in this case than that of any low-index surface facet of bulk Au crystal. This fact can be explained by the complex structure of the surface with an extensive number of broken bonds due to edge and corner atoms. A similar trend was obtained also for the case of cuboctahedrons. Since the exact surface area of the nanoparticles is an ill-defined quantity, we have introduced the surface-induced excess energy and discuss this quantity as a function of (i) number of atoms forming the nano-object or (ii) characteristic size of the nano-object. In case (i), a universal power-law behaviour was obtained independent of the nanoparticle shape. Importantly, we show that the size-dependence of the surface energy is hugely reduced, if the surface area correction is considered due to its expansion by the electronic cloud, a phenomenon specifically important for small nanoparticles.
TmSpz4 Plays an Important Role in Regulating the Production of Antimicrobial Peptides in Response to Escherichia coli and Candida albicans Infections

Spätzle family proteins activate the Toll pathway and induce antimicrobial peptide (AMP) production against microbial infections. However, the functional importance of Tmspätzle4 (TmSpz4) in the immune response of Tenebrio molitor has not been reported. Therefore, here, we have identified and functionally characterized the role of TmSpz4 against bacterial and fungal infections. We showed that TmSpz4 expression was significantly induced in hemocytes at 6 h post-injection with Escherichia coli, Staphylococcus aureus, and Candida albicans. TmSpz4 knock-down significantly reduced larval survival against E. coli and C. albicans. To understand the reason for the survivability difference, the role of TmSpz4 in AMP production was examined in TmSpz4-silenced larvae following microbe injection. The AMPs that are active against Gram-negative bacteria, including TmTenecin-2, TmTenecin-4, TmAttacin-1a, TmDefensin-2, and TmCecropin-2, were significantly downregulated in response to E. coli in TmSpz4-silenced larvae. Similarly, the expression of TmTenecin-1, TmTenecin-3, TmThaumatin-like protein-1 and -2, TmDefensin-1, TmDefensin-2, and TmCecropin-2 were downregulated in response to C. albicans in TmSpz4-silenced larvae. In addition, the transcription factor NF-κB (TmDorX1 and TmDorX2) expression was significantly suppression in TmSpz4-silenced larvae. In conclusion, these results suggest that TmSpz4 plays a key role in regulating immune responses of T. molitor against to E. coli and C. albicans.
Risk factors of the progression to hypertension and characteristics of natural history during progression: A national cohort study

Background Although the high disease burden that results from cardiovascular complications of hypertension, factors related to the progression to hypertension in the normotensive population are not actively reported. The purpose of this study was to estimate the rate of the progression to hypertension and to reveal the associated risk factors. Methods The study included normotensive participants from the National Health Insurance Service-National Health Screening Cohort, and contained a 10% sample of all adults who received a national health screening test in either 2002 or 2003. At the end of the study in 2015, the patients were divided into two groups based on whether or not they progressed to hypertension. Cox proportional hazard modeling was performed to identify risk factors for progression. Subgroup analysis using logistic regression was employed to reveal factors influencing the different natural history of the progression. Results Among the 75,335 included participants, the progression rate to hypertension was 66.39% (50,013), with an adjusted incidence rate of 8.62 per 100 person-year in the aged 40–64 group and 12.68 in the aged 65 or above group. Age, BMI, hemoglobin, and family history of hypertension and other diseases were related to the progression. Among the progression group, 78.21% (39,116) participants skipped a pre-hypertensive status; this group consisted of older females with lower pulse pressure and more alcohol consumption compared to people who had pre-hypertensive status before the progression. Conclusion Substantial risk factors for the progression to hypertension should be carefully managed even in normotensive participants who receive health screening tests.
Trunk Refugia: A Simple, Inexpensive Method for Sampling Tree Trunk Arthropods

Abstract Trees host a large share of the global arthropod diversity. Several methodologies have been described to sample arthropods from trees, ranging from active sampling techniques (e.g., visual searching, beating, or shaking the branches) to passive sampling devices. The majority of these collection techniques are destructive, and do not specifically target the tree trunk arthropod fauna. Here, we describe an alternative sampling method called trunk refugia (TR). TR are cylindrical shelters made of corrugated cardboard that can be secured to trees using string, and can remain exposed for varying time periods. These refugia are inexpensive, easy to use, and suitable to monitor a diverse array of insects and arachnids. Moreover, TR are nonlethal sampling tools, and allow collecting live individuals for behavioral studies or for rearing.
A Pharmacogenomic Dissection of a Rosuvastatin-Induced Rhabdomyolysis Case Evokes the Polygenic Nature of Adverse Drug Reactions

Abstract Rosuvastatin, is a widely-used statin for the treatment of hypercholesterolemia and the prevention of cardiovascular diseases. Although rosuvastatin is well tolerated, about 3/10.000 patients can suffer severe myopathy. Rhabdomyolysis is a severe medical condition that causes injury to the skeletal muscle, electrolyte imbalances, acute renal failure and extreme creatine kinase (CK) elevation. Little is known regarding the molecular involvement of rosuvastatin-induced rhabdomyolysis (RIR). It has been demonstrated that genomic variants associated with decreased enzymatic activity of proteins are important determinants in plasmatic and skeletal muscle distribution of rosuvastatin and its toxicity. Until now, no interactions of ticagrelor, ezetimibe and rosuvastatin have been described with the consideration of pharmacogenomics predisposition. The present report involves a whole-exome sequencing (WES), in a patient affected by rosuvastatin-induced rhabdomyolysis. A pharmacogenomic dissection was performed by analyzing a comprehensive subset of candidate genes (n=160) potentially related to RIR. The genes were selected according to their implication in drug metabolism or inherited myopathies. Using an innovative approach of bioinformatics analysis, considering rare and common variants, we identified 19 genomic variations potentially related to the pharmacokinetic/pharmacodynamic modifications of rosuvastatin, ezetimibe and ticagrelor. The affected genes are involved in Phase I metabolism (CYP2C19, CYP2E1, CYP1A1, CYP2D6 and CYP2C9), Phase II metabolism (UGT2B15 and UGT2B7), influx transportation (SLCO1B3 and SLCO2B1), efflux transportation (ABCG8, ABCB11, ABCC4 and ABCB1), drug targeting (NPC1L1) and inherited myopathy etiology (OBSCN). We report three rare, potentially pathogenic molecular variants in CYP2C19, NPC1L1 and OBSCN genes. Pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles in several pharmacogenes involved in drug toxicity. The whole-exome sequencing and bioinformatics analysis presented here represents an innovative way to identify genomic variants contributing with RIR´s origin and evokes the polygenic nature of adverse drug reactions.
Fasciola hepatica: the dispersal of cercariae shed by the snail Galba truncatula

Field investigations in 14 wild watercress beds located in the French region of Limousin, a known endemic area for distomatosis, were performed for three years to determine the distance that cercariae of Fasciola hepatica can reach in water before their encystment on the host plant. Each bed was located on the course of an open drainage furrow, while snails (Galba truncatula) lived upstream around the emergence of a source. Five plant species were collected in early April and examined to find metacercariae. Most cysts were noted on Nasturtium officinale (188 on 48.7 kg of dripped plants), followed by Helosciadium nodiflorum (125 on 33.4 kg). On the other plant species, there were few larvae. Most cercariae encysted on the plants growing in the most upstream part of each bed, usually on the first 50 cm in length. When water in the beds was fast running, the distribution of metacercariae was more limited and their number was fewer than those in the beds fed by a slow flow of water. Cercariae were able to swim or were carried away by the current up to a mean of 5 m in slow-flow waters before encysting; this distance was only 4 m in faster waters. Plants growing on the most upstream section of a watercress bed located in a drainage furrow are the most used by cercariae for their encystment, when snails live around the emergence of a source. The speed of the water current affected the number and distribution of metacercariae in the bed.
Glucocerebrosidase: Functions in and Beyond the Lysosome

Glucocerebrosidase (GCase) is a retaining β-glucosidase with acid pH optimum metabolizing the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose. Inherited deficiency of GCase causes the lysosomal storage disorder named Gaucher disease (GD). In GCase-deficient GD patients the accumulation of GlcCer in lysosomes of tissue macrophages is prominent. Based on the above, the key function of GCase as lysosomal hydrolase is well recognized, however it has become apparent that GCase fulfills in the human body at least one other key function beyond lysosomes. Crucially, GCase generates ceramides from GlcCer molecules in the outer part of the skin, a process essential for optimal skin barrier property and survival. This review covers the functions of GCase in and beyond lysosomes and also pays attention to the increasing insight in hitherto unexpected catalytic versatility of the enzyme.
Adherence to a Health Literacy and Healthy Lifestyle with Improved Blood Pressure Control in Iran

Introduction and Aim High blood pressure is the leading and most important modifiable risk factor for cardiovascular disease. Health literacy and lifestyle are two paramount key factors behind better control of hypertension. This study was conducted to examine the current situation of health literacy and health-promoting lifestyle and its association with blood pressure control among people affected by hypertension in the population over age 30 of Northwest Iran. Patients and Methods This was a cross-sectional study conducted in October and December 2018 on the over 30-year-old population among subjects suffering from hypertension (n= 210). A self-reported questionnaire was used for assessing health literacy dimensions and lifestyle. Results In hierarchical linear analysis, the HL explained 33.9% of the variance in healthy lifestyle. Among HL dimensions, the ability to access health information and decision-making were significantly associated with healthy lifestyle. The health literacy dimensions contributed to an additional significant increase in 4.7% of the variance explained in hypertension, furthermore, the health-promoting lifestyle items were explained an additional 14.8% of the hypertension variance. In total, lifestyle and health literacy dimensions were able to explain 21.7% of the variance in hypertension. Conclusion Our study encourages efforts to monitor health literacy in people with hypertension and investigate associations with involvement with health-promoting lifestyle.
MicroRNA‑34a expression affects breast cancer invasion in vitro and patient survival via downregulation of E2F1 and E2F3 expression.

Breast cancer is the most common cancer type and the leading cause of cancer‑associated mortality in women across the majority of countries. In general, the incidence of breast cancer has been decreasing in developed countries over the previous 20 years, while it has increased in the other areas, such as the Asian‑Pacific region. MicroRNA‑34a (miR‑34a) targets stem cell‑associated transcription factors E2F1/E2F3, and may have clinical relevance in breast cancer. The present study aimed to investigate the association between miR‑34a/E2F1/E2F3 and patient survival in breast cancer, as well as the underlying molecular mechanism of miR‑34a in suppressing factors associated with tumor aggressiveness in vitro. Kaplan‑Meier survival curves were constructed and a meta‑analysis was performed to analyze the association of miR‑34a, E2F1 and E2F3 expression and overall survival in breast cancer, and the differential expression levels of E2F1 and E2F3 between breast cancer and normal breast tissues was assessed using publicly accessed datasets. Then 2D and 3D experiments on cell cultures were performed in vitro on both T‑47D and MDA‑MB‑231 cells to investigate the cancer biology of miR‑34a and its effect on E2F1 and E2F3 expression using reverse transcription‑quantitative PCR. Then, caspase‑3 (CASP3) activity was measured using a CaspACE™ assay system. E2F1 and E2F3 expression levels were upregulated in breast cancer, compared with normal breast tissues. Both high miR‑34a, and low E2F1 and E2F3 mRNA levels were positively associated with longer survival times in patients with breast cancer. The in vitro 2D and 3D cell experiments revealed that overexpression of miR‑34a significantly downregulated the expression of E2F1 and E2F3, and increased CASP3 activity in both T‑47D and MDA‑MB‑231 cells, and that miR‑34a treatment inhibited tumor cell proliferation, migration and invasiveness, as well as 3D spheroid formation. Thus, miR‑34a influences the aggressiveness of breast cancer and patient survival, and is a potential therapeutic tool in the clinical management of breast cancer.
The Neurochemistry of Autism

Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundred references were collected through electronic database searching in Medline and EMBASE (Ovid), Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI).