bluuebunny/crossref_metadata_2025 huggingface dataset:
Betulinic Acid Affects the Energy-Related Proteomic Profiling in Pancreatic Ductal Adenocarcinoma Cells
Authors: Chiu Ching-Feng , Chang Hsin-Yi , Huang Chun-Yine , Mau Chen-Zou , Kuo Tzu-Ting , Lee Hsiu-Chuan , Huang Shih-Yi
Published: April 2021

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of <8%. Therefore, finding new treatment strategies against PDAC cells is an imperative issue. Betulinic acid (BA), a plant-derived natural compound, has shown great potential to combat cancer owing to its versatile physiological functions. In this study, we observed the impacts of BA on the cell viability and migratory ability of PDAC cell lines, and screened differentially expressed proteins (DEPs) by an LC-MS/MS-based proteomics analysis. Our results showed that BA significantly inhibited the viability and migratory ability of PDAC cells under a relatively low dosage without affecting normal pancreatic cells. Moreover, a functional analysis revealed that BA-induced downregulation of protein clusters that participate in mitochondrial complex 1 activity and oxidative phosphorylation, which was related to decreased expressions of RNA polymerase mitochondrial (POLRMT) and translational activator of cytochrome c oxidase (TACO1), suggesting that the influence on mitochondrial function explains the effect of BA on PDAC cell growth and migration. In addition, BA also dramatically increased Apolipoprotein A1 (APOA1) expression and decreased NLR family CARD domain-containing protein 4 (NLRC4) expression, which may be involved in the dampening of PDAC migration. Notably, altered expression patterns of APOA1 and NLRC4 indicated a favorable clinical prognosis of PDAC. Based on these findings, we identified potential proteins and pathways regulated by BA from a proteomics perspective, which provides a therapeutic window for PDAC.
Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data
Authors: López-López Edgar , Cerda-García-Rojas Carlos M. , Medina-Franco José L.
Published: April 2021

Inhibiting the tubulin-microtubules (Tub-Mts) system is a classic and rational approach for treating different types of cancers. A large amount of data on inhibitors in the clinic supports Tub-Mts as a validated target. However, most of the inhibitors reported thus far have been developed around common chemical scaffolds covering a narrow region of the chemical space with limited innovation. This manuscript aims to discuss the first activity landscape and scaffold content analysis of an assembled and curated cell-based database of 851 Tub-Mts inhibitors with reported activity against five cancer cell lines and the Tub-Mts system. The structure–bioactivity relationships of the Tub-Mts system inhibitors were further explored using constellations plots. This recently developed methodology enables the rapid but quantitative assessment of analog series enriched with active compounds. The constellations plots identified promising analog series with high average biological activity that could be the starting points of new and more potent Tub-Mts inhibitors.
Heteroleptic LaIII Anilate/Dicarboxylate Based Neutral 3D-Coordination Polymers
Authors: Trofimova Olesya Y. , Maleeva Arina V. , Ershova Irina V. , Cherkasov Anton V. , Fukin Georgy K. , Aysin Rinat R. , Kovalenko Konstantin A. , Piskunov Alexandr V.
Published: April 2021

Three new 3D metal–organic frameworks of lanthanum based on mixed anionic ligands, [(La2(pQ)2(BDC)4)·4DMF]n, [(La2(pQ)2(DHBDC)4)·4DMF]n, [(La2(CA)2(BDC)4)·4DMF]n (pQ—dianion of 2,5-dihydroxy-3,6-di-tert-butyl-para-quinone, CA—dianion of chloranilic acid, BDC-1,4-benzenedicarboxylate, DHBDC-2,5-dihydroxy-1,4-benzenedicarboxylate and DMF-N,N′-dimethylformamide), were synthesized using solvothermal methodology. Coordination polymers demonstrate the rare xah or 4,6T187 topology of a 3D framework. The homoleptic 2D-coordination polymer [(La2(pQ)3)·4DMF]n was obtained as a by-product in the course of synthetic procedure optimization. The thermal stability, spectral characteristics and porosity of coordination polymers were investigated.
iT4SE-EP: Accurate Identification of Bacterial Type IV Secreted Effectors by Exploring Evolutionary Features from Two PSI-BLAST Profiles
Authors: Han Haitao , Ding Chenchen , Cheng Xin , Sang Xiuzhi , Liu Taigang
Published: April 2021

Many gram-negative bacteria use type IV secretion systems to deliver effector molecules to a wide range of target cells. These substrate proteins, which are called type IV secreted effectors (T4SE), manipulate host cell processes during infection, often resulting in severe diseases or even death of the host. Therefore, identification of putative T4SEs has become a very active research topic in bioinformatics due to its vital roles in understanding host-pathogen interactions. PSI-BLAST profiles have been experimentally validated to provide important and discriminatory evolutionary information for various protein classification tasks. In the present study, an accurate computational predictor termed iT4SE-EP was developed for identifying T4SEs by extracting evolutionary features from the position-specific scoring matrix and the position-specific frequency matrix profiles. First, four types of encoding strategies were designed to transform protein sequences into fixed-length feature vectors based on the two profiles. Then, the feature selection technique based on the random forest algorithm was utilized to reduce redundant or irrelevant features without much loss of information. Finally, the optimal features were input into a support vector machine classifier to carry out the prediction of T4SEs. Our experimental results demonstrated that iT4SE-EP outperformed most of existing methods based on the independent dataset test.
Wound Healing Activity of α-Pinene and α-Phellandrene
Authors: Salas-Oropeza Judith , Jimenez-Estrada Manuel , Perez-Torres Armando , Castell-Rodriguez Andres Eliu , Becerril-Millan Rodolfo , Rodriguez-Monroy Marco Aurelio , Jarquin-Yañez Katia , Canales-Martinez Maria Margarita
Published: April 2021

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. Recently, it was shown that the essential oil (EO) of B. morelensis has wound healing activity, accelerating cutaneous wound closure and generating scars with good tensile strength. α-pinene (PIN) and α-phellandrene (FEL) are terpenes that have been found in this EO, and it has been shown in different studies that both have anti-inflammatory activity. The aim of this study was to determine the wound healing activity of these two terpenes. The results of in vitro tests demonstrate that PIN and FEL are not cytotoxic at low concentrations and that they do not stimulate fibroblast cell proliferation. In vivo tests showed that the terpenes produce stress-resistant scars and accelerate wound contraction, due to collagen deposition from the early stages, in wounds treated with both terpenes. Therefore, we conclude that both α-pinene and α-phellandrene promote the healing process; this confirms the healing activity of the EO of B. morelensis, since having these terpenes as part of its chemical composition explains part of its demonstrated activity.
Formulation and Evaluation of a Clove Oil-Encapsulated Nanofiber Formulation for Effective Wound-Healing
Authors: Hameed Misbah , Rasul Akhtar , Waqas Muhammad , Saadullah Malik , Aslam Nosheen , Abbas Ghulam , Latif Sumera , Afzal Hafsa , Inam Sana , Akhtar Shah Pervaiz
Published: April 2021

Wound-healing is complicated process that is affected by many factors, especially bacterial infiltration at the site and not only the need for the regeneration of damaged tissues but also the requirement for antibacterial, anti-inflammatory, and analgesic activity at the injured site. The objective of the present study was to develop and evaluate the natural essential oil-containing nanofiber (NF) mat with enhanced antibacterial activity, regenerative, non-cytotoxic, and wound-healing potential. Clove essential oil (CEO) encapsulated in chitosan and poly-ethylene oxide (PEO) polymers to form NFs and their morphology was analyzed using scanning electron microscopy (SEM) that confirmed the finest NFs prepared with a diameter of 154 ± 35 nm. The successful incorporation of CEO was characterized by Fourier transform infra-red spectroscopy (FTIR) and X-ray diffractometry (XRD). The 87.6 ± 13.1% encapsulation efficiency and 8.9 ± 0.98% loading of CEO was observed. A total of 79% release of CEO was observed in acidic pH 5.5 with 117% high degree of swelling. The prepared NF mat showed good antibacterial activity against Staphylococcus aureus and Escherichia coli and non-cytotoxic behavior against human fibroblast cell lines and showed good wound-healing potential.
Neuroprotective Effects of Curcumin in Methamphetamine-Induced Toxicity
Authors: Ryskalin Larisa , Puglisi-Allegra Stefano , Lazzeri Gloria , Biagioni Francesca , Busceti Carla L. , Balestrini Linda , Fornasiero Andrea , Leone Stefano , Pompili Elena , Ferrucci Michela , Fornai Francesco
Published: April 2021

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophagy.
The Role of Resveratrol in Human Male Fertility
Authors: Mongioì Laura M. , Perelli Sarah , Condorelli Rosita A. , Barbagallo Federica , Crafa Andrea , Cannarella Rossella , La Vignera Sandro , Calogero Aldo E.
Published: April 2021

Resveratrol (RSV) (3,4′,5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer’s disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.
Broadband Absorption Based on Thin Refractory Titanium Nitride Patterned Film Metasurface
Authors: Huo Dewang , Ma Xinyan , Su Hang , Wang Chao , Zhao Hua
Published: April 2021

In this paper, a thin metasurface perfect absorber based on refractory titanium nitride (TiN) is proposed. The size parameter of the metasurface is investigated based on the finite difference time domain method and transfer matrix method. With only a 15-nm-thick TiN layer inside the silica/TiN/silica stacks standing on the TiN substrate, the near-perfect absorption throughout the visible regime is realized. The cross-talk between the upper and lower dielectric layers enables the broadening of the absorption peak. After patterning the thin film into a nanodisk array, the resonances from the nanodisk array emerge to broaden the high absorption bandwidth. As a result, the proposed metasurface achieves perfect absorption in the waveband from 400 to 2000 nm with an average absorption of 95% and polarization-insensitivity under the normal incidence. The proposed metasurface maintains average absorbance of 90% up to 50-degree oblique incidence for unpolarized light. Our work shows promising potential in the application of solar energy harvesting and other applications requiring refractory metasurfaces.
Structural and Electrochemical Analysis of CIGS: Cr Crystalline Nanopowders and Thin Films Deposited onto ITO Substrates
Authors: Saber Suzan , Marí Bernabé , Andrio Andreu , Escorihuela Jorge , Khattab Nagwa , Eid Ali , Nahrawy Amany El , Abo Aly Mohamed , Compañ Vicente
Published: April 2021

A new approach for the synthesis of nanopowders and thin films of CuInGaSe2 (CIGS) chalcopyrite material doped with different amounts of Cr is presented. The chalcopyrite material CuInxGa1 − xSe2 was doped using Cr to form a new doped chalcopyrite with the structure CuInxCryGa1 − x − ySe2, where x = 0.4 and y = 0.0, 0.1, 0.2, or 0.3. The electrical properties of CuInx CryGa1 − x − ySe2 are highly dependent on the Cr content and results show these materials as promising dopants for the fabrication thin film solar cells. The CIGS nano-precursor powder was initially synthesized via an autoclave method, and then converted into thin films over transparent substrates. Both crystalline precursor powders and thin films deposited onto ITO substrates following a spin-coating process were subsequently characterized using XRD, SEM, HR-TEM, UV–visible and electrochemical impedance spectroscopy (EIS). EIS measurement was performed to evaluate the dc-conductivity of these novel materials as conductive films to be applied in solar cells.
Influence of Cu on the Improvement of Magnetic Properties and Structure of L10 FePt Nanoparticles
Authors: Zhang Luran , Du Xinchen , Lu Hongjie , Gao Dandan , Liu Huan , Lin Qilong , Cao Yongze , Xie Jiyang , Hu Wanbiao
Published: April 2021

L10 ordered FePt and FePtCu nanoparticles (NPs) with a good dispersion were successfully fabricated by a simple, green, one-step solid-phase reduction method. Fe (acac)3, Pt (acac)2, and CuO as the precursors were dispersed in NaCl and annealed at different temperatures with an H2-containing atmosphere. As the annealing temperature increased, the chemical order parameter (S), average particle size (D), coercivity (Hc), and saturation magnetization (Ms) of FePt and FePtCu NPs increased and the size distribution range of the particles became wider. The ordered degree, D, Hc, and Ms of FePt NPs were greatly improved by adding 5% Cu. The highest S, D, Hc, and Ms were obtained when FePtCu NPs annealed at 750 °C, which were 0.91, 4.87 nm, 12,200 Oe, and 23.38 emu/g, respectively. The structure and magnetic properties of FePt and FePtCu NPs at different annealing temperatures were investigated and the formation mechanism of FePt and FePtCu NPs were discussed in detail.
Hemocompatibility of Nanotitania-Nanocellulose Hybrid Materials
Authors: Svensson Fredric G. , Manivel Vivek Anand , Seisenbaeva Gulaim A. , Kessler Vadim G. , Nilsson Bo , Ekdahl Kristina N. , Fromell Karin
Published: April 2021

In order to develop a new type of improved wound dressing, we combined the wound healing properties of nanotitania with the advantageous dressing properties of nanocellulose to create three different hybrid materials. The hemocompatibility of the synthesized hybrid materials was evaluated in an in vitro human whole blood model. To our knowledge, this is the first study of the molecular interaction between hybrid nanotitania and blood proteins. Two of the hybrid materials prepared with 3 nm colloidal titania and 10 nm hydrothermally synthesized titania induced strong coagulation and platelet activation but negligible complement activation. Hence, they have great potential as a new dressing for promoting wound healing. Unlike the other two, the third hybrid material using molecular ammonium oxo-lactato titanate as a titania source inhibited platelet consumption, TAT generation, and complement activation, apparently via lowered pH at the surface interface. It is therefore suitable for applications where a passivating surface is desired, such as drug delivery systems and extracorporeal circuits. This opens the possibility for a tailored blood response through the surface functionalization of titania.
High-Performance Non-Volatile InGaZnO Based Flash Memory Device Embedded with a Monolayer Au Nanoparticles
Authors: Naqi Muhammad , Kwon Nayoung , Jung Sung , Pujar Pavan , Cho Hae , Cho Yong , Cho Hyung , Lim Byungkwon , Kim Sunkook
Published: April 2021

Non-volatile memory (NVM) devices based on three-terminal thin-film transistors (TFTs) have gained extensive interest in memory applications due to their high retained characteristics, good scalability, and high charge storage capacity. Herein, we report a low-temperature (<100 °C) processed top-gate TFT-type NVM device using indium gallium zinc oxide (IGZO) semiconductor with monolayer gold nanoparticles (AuNPs) as a floating gate layer to obtain reliable memory operations. The proposed NVM device exhibits a high memory window (ΔVth) of 13.7 V when it sweeps from −20 V to +20 V back and forth. Additionally, the material characteristics of the monolayer AuNPs (floating gate layer) and IGZO film (semiconductor layer) are confirmed using transmission electronic microscopy (TEM), atomic force microscopy (AFM), and x-ray photoelectron spectroscopy (XPS) techniques. The memory operations in terms of endurance and retention are obtained, revealing highly stable endurance properties of the device up to 100 P/E cycles by applying pulses (±20 V, duration of 100 ms) and reliable retention time up to 104 s. The proposed NVM device, owing to the properties of large memory window, stable endurance, and high retention time, enables an excellent approach in futuristic non-volatile memory technology.
Effects of Ipriflavone-Loaded Mesoporous Nanospheres on the Differentiation of Endothelial Progenitor Cells and Their Modulation by Macrophages
Authors: Casarrubios Laura , Polo-Montalvo Alberto , Serrano María , Feito María , Vallet-Regí María , Arcos Daniel , Portolés María
Published: April 2021

Angiogenic biomaterials are designed to promote vascularization and tissue regeneration. Nanoparticles of bioactive materials loaded with drugs represent an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. In this work, porcine endothelial progenitor cells (EPCs), essential for blood vessel formation, were isolated and characterized to evaluate the in vitro effects of unloaded (NanoMBGs) and ipriflavone-loaded nanospheres (NanoMBG-IPs), which were designed to prevent osteoporosis. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) was studied in EPCs under different culture conditions: (a) treatment with NanoMBGs or NanoMBG-IPs, (b) culture with media from basal, M1, and M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, (c) coculture with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and (d) coculture with M2d angiogenic macrophages. The endocytic mechanisms for nanosphere incorporation by EPCs were identified using six different endocytosis inhibitors. The results evidence the great potential of these nanomaterials to enhance VEGFR2 expression and angiogenesis, after intracellular incorporation by EPCs through clathrin-dependent endocytosis, phagocytosis, and caveolae-mediated uptake. The treatment of EPCs with basal, M1, and M2 macrophage culture media and EPC/macrophage coculture studies also confirmed the angiogenic effect of these nanospheres on EPCs, even in the presence of phagocytic cells.
Impedance Spectroscopic Study of Nickel Sulfide Nanostructures Deposited by Aerosol Assisted Chemical Vapor Deposition Technique
Authors: Iram Sadia , Mahmood Azhar , Ehsan Muhammad Fahad , Mumtaz Asad , Sohail Manzar , Sitara Effat , Bukhari Syeda Aqsa Batool , Gul Sumia , Fatima Syeda Arooj , Khan Muhammad Zarrar , Shaheen Rubina , Malik Sajid Nawaz , Malik Mohammad Azad
Published: April 2021

This research aims to synthesize the Bis(di-isobutyldithiophosphinato) nickel (II) complex [Ni(iBu2PS2)] to be employed as a substrate for the deposition of nickel sulfide nanostructures, and to investigate its dielectric and impedance characteristics for applications in the electronic industry. Various analytical tools including elemental analysis, mass spectrometry, IR, and TGA were also used to further confirm the successful synthesis of the precursor. NiS nanostructures were grown on the glass substrates by employing an aerosol assisted chemical vapor deposition (AACVD) technique via successful decomposition of the synthesized complex under variable temperature conditions. XRD, SEM, TEM, and EDX methods were well applied to examine resultant nanostructures. Dielectric studies of NiS were carried out at room temperature within the 100 Hz to 5 MHz frequency range. Maxwell-Wagner model gave a complete explanation of the variation of dielectric properties along with frequency. The reason behind high dielectric constant values at low frequency was further endorsed by Koops phenomenological model. The efficient translational hopping and futile reorientation vibration caused the overdue exceptional drift of ac conductivity (σac) along with the rise in frequency. Two relaxation processes caused by grains and grain boundaries were identified from the fitting of a complex impedance plot with an equivalent circuit model (Rg Cg) (Rgb Qgb Cgb). Asymmetry and depression in the semicircle having center present lower than the impedance real axis gave solid justification of dielectric behavior that is non-Debye in nature.
Fully Developed Opposing Mixed Convection Flow in the Inclined Channel Filled with a Hybrid Nanofluid
Authors: You Xiangcheng , Li Shiyuan
Published: April 2021

This paper studies the convective heat transfer of a hybrid nanofluid in the inclined channel, whose walls are both heated by the uniform heat flux. The governing ordinary differential equations are made nondimensional and solved analytically, in which explicit distributions of velocity, temperature and pressure are obtained. The effects of flow reversal, wall skin friction and Nusselt number with the hybrid nanofluid depend on the nanoparticle volume fractions and pressure parameters. The obtained results indicate that the nanoparticle volume fractions play a key role in delaying the occurrence of the flow reversal. The hybrid nanofluids hold more delayed range than conventional nanofluids, which is about 2.5 times that of nanofluids. The calculations have been compared with the base fluid, nanofluid and two kinds of hybrid models (type II and type III). The hybrid model of type III is useful and simplified in that it omits the nonlinear terms due to the interaction of different nanoparticle volumetric fractions, with the relative error less than 3%. More results are discussed in the results section below.
Fruit and Vegetable Intake and Telomere Length in a Random Sample of 5448 U.S. Adults
Authors: Tucker Larry A.
Published: April 2021

The relationship between fruit and vegetable intake and telomere length was examined using a cross-sectional design and an NHANES random sample of 5448 U.S. adults. Fruit and vegetable (F&V) consumption was assessed using a 24 h recall, and telomere length, an index of cellular aging, was measured using the quantitative polymerase chain reaction method. Telomere length was linearly related to F&V intake when combined (F = 22.7, p < 0.0001) and also when separated as fruit (F = 7.2, p < 0.0121) or vegetables (F = 15.4, p < 0.0005), after adjusting for covariates. Specifically, telomeres were 27.8 base pairs longer for each 100 g (3.5 ounces) of F&V consumed. Because each additional year of chronological age was associated with telomeres that were 14.9 base pairs shorter, when women and men were analyzed together, results indicated that a 100 g (3.5 oz) per day increment in F&V corresponded with 1.9 years less biological aging. When the 75th percentile of F&V intake was compared to the 25th, the difference was 4.4 years of cellular aging. When separated by sex, fruits and vegetables were both related to telomere length in women, but only vegetable intake was predictive of telomere length in men. In conclusion, evidence based on a random sample of U.S. adults indicates that the more the servings of F&V, the longer telomeres tend to be.
Difference and Variance in Nutrient Intake by Age for Older Adults Living Alone in Japan: Comparison of Dietary Reference Intakes for the Japanese Population
Authors: Ishikawa Midori , Yokomichi Hiroshi , Yokoyama Tetsuji
Published: April 2021

This study aimed to estimate the distribution of usual intakes in protein, sodium, potassium, and calcium by age group and assessed whether proportions of deficiencies/excesses of each nutrient would occur more in older age via a comparison with the dietary reference intakes for the Japanese population (DRIs_J). A cross-sectional analysis was conducted using a database of the 2-day nutrient intake of 361 Japanese people aged 65–90 years. The AGEVAR MODE was used to estimate usual intake. Percentile curves using estimated distribution by sex and age and usual nutrient intake were compared to those of the DRIs_J. The usual intake of protein (male and female) and potassium and calcium (female) were lower with older age. Within-individual variance of protein in female (p = 0.037) and calcium in male (p = 0.008) subjects were considerably lower with older age. The proportion of deficiencies in protein (male and female), potassium (female), and calcium (female) were higher with older age. However, the proportion of people with excess salt (converted from sodium; male and female) did not differ by age. The variances found herein could be important for enhancing the understanding of differences in dietary intake by age.
The Effect of Different Postprandial Exercise Types on Glucose Response to Breakfast in Individuals with Type 2 Diabetes
Authors: Bellini Alessio , Nicolò Andrea , Bulzomì Rocco , Bazzucchi Ilenia , Sacchetti Massimo
Published: April 2021

Postprandial exercise represents an important tool for improving the glycemic response to a meal. This study evaluates the effects of the combination and sequence of different exercise types on the postprandial glycemic response in patients with type 2 diabetes. In this repeated-measures crossover study, eight patients with type 2 diabetes performed five experimental conditions in a randomized order: (i) uninterrupted sitting (CON); (ii) 30 min of moderate intensity aerobic exercise (walking) (A); (iii) 30 min of combined aerobic and resistance exercise (AR); (iv) 30 min of combined resistance and aerobic exercise (RA); and (v) 15 min of resistance exercise (R). All the exercise sessions started 30 min after the beginning of a standardized breakfast. All the exercise conditions showed a significant attenuation of the post-meal glycemic excursion (P < 0.003) and the glucose incremental area under the curve at 0–120 min (P < 0.028) and 0–180 min (P < 0.048) compared with CON. A greater reduction in the glycemic peak was observed in A and AR compared to RA (P < 0.02). All the exercise types improved the post-meal glycemic response in patients with type 2 diabetes, with greater benefits when walking was performed alone or before resistance exercise.
Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development
Authors: Vancells Lujan Pau , Viñas Esmel Esther , Sacanella Meseguer Emilio
Published: April 2021

NAFLD is the world’s most common chronic liver disease, and its increasing prevalence parallels the global rise in diabetes and obesity. It is characterised by fat accumulation in the liver evolving to non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead to liver fibrosis and cirrhosis. Currently, there is no effective pharmacotherapeutic treatment for NAFLD. Treatment is therefore based on lifestyle modifications including changes to diet and exercise, although it is unclear what the most effective form of intervention is. The aim of this review, then, is to discuss the role of specific nutrients and the effects of different dietary interventions on NAFLD. It is well established that an unhealthy diet rich in calories, sugars, and saturated fats and low in polyunsaturated fatty acids, fibre, and micronutrients plays a critical role in the development and progression of this disease. However, few clinical trials have evaluated the effects of nutrition interventions on NAFLD. We, therefore, summarise what is currently known about the effects of macronutrients, foods, and dietary patterns on NAFLD prevention and treatment. Most current guidelines recommend low-calorie, plant-based diets, such as the Mediterranean diet, as the most effective dietary pattern to treat NAFLD. More clinical trials are required, however, to identify the best evidence-based dietary treatment approach.
Phase Angle as an Easy Diagnostic Tool of Meta-Inflammation for the Nutritionist
Authors: Barrea Luigi , Muscogiuri Giovanna , Pugliese Gabriella , Laudisio Daniela , de Alteriis Giulia , Graziadio Chiara , Colao Annamaria , Savastano Silvia
Published: April 2021

Phase angle (PhA), a noninvasive bioimpedance marker, is a useful tool for nutritional screening in several diseases. C-reactive protein (CRP), a strong risk factor for metabolic and cardiovascular diseases, is a commonly used biomarker of meta-inflammation. As both PhA and CRP are influenced by age, BMI, and nutritional status, and exhibit a clear sex dimorphism, we examined the association between PhA and CRP levels in 1855 subjects (680 males and 1175 females), aged 18–59 years, with BMIs ranging from 19.5 to 69.4 kg/m2, stratified according to sex. PhA values and CRP levels were significantly lower in females than males (p < 0.001), while the adherence to the Mediterranean diet (MD) was lower in males compared to females (p < 0.001). After adjusting for age, physical activity, BMI, waist circumference, and adherence to the MD, PhA remained negatively associated with CRP levels in both genders (p < 0.001). In the ROC analysis, PhA ≤ 5.5° in males and ≤5.4° in females were the threshold values predicting increased hs-CRP levels. These results suggested that PhA might represent a valid predictor of CRP levels in both sexes regardless of body weight and adherence to the MD, which avoids the collection of blood sampling and expensive biochemical assays.
Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer
Authors: Guha Snigdha , Alvarez Sophie , Majumder Kaustav
Published: April 2021

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (Papp) of 1.56 × 10−6 ± 0.7 × 10−6 cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10−6 ± 0.6 × 10−6 cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the Papp of γ-EV to 4.36 × 10−6 ± 0.16 × 10−6 cm/s (p < 0.001), while theaflavin 3′-gallate and Gly-Sar significantly decreased the Papp (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular.
The Effect of Perioperative Administration of Probiotics on Colorectal Cancer Surgery Outcomes
Authors: Pitsillides Louise , Pellino Gianluca , Tekkis Paris , Kontovounisios Christos
Published: April 2021

The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome’s balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.
α-(Imino)pyridyldifluoroethyl Phosphonates: Novel Promising Building Blocks in Synthesis of Biorelevant Aminophosphonic Acids Derivatives
Authors: Shavrina Oksana , Bezgubenko Lyudmyla , Bezdudny Andrii , Onys’ko Petro , Rassukana Yuliya
Published: April 2021

A convenient synthetic approach to previously unknown NH-iminophosphonates bearing 2-, 3-, and 4-pyridyldifluoromethyl groups at the imine carbon atom was developed. The synthetic potential of these novel building blocks was demonstrated by their conversion into highly functionalized acyclic and heterocyclic aminophosphonates and phosphonic acids combining in their structure biorelevant aminophosphonic fragment, difluoromethyl group, and pyridyl, piperidyl, thiazolidin-4-one, or thiazidinan-4-one heterocyclic moieties in a single molecular platform.
Z,E-Isomerism in a Series of Substituted Iminophosphonates: Quantum Chemical Research
Authors: Rozhenko Alexander B. , Kyrylchuk Andrey A. , Lapinska Yuliia O. , Rassukana Yuliya V. , Trachevsky Vladimir V. , Pirozhenko Volodymyr V. , Leszczynski Jerzy , Onysko Petro P.
Published: April 2021

Esters of iminophosphonic acids (iminophosphonates, or IPs), including a fragment, >P(=O)-C=N, can be easily functionalized, for instance to aminophosphonic acids with a wide range of biological activity. Depending on the character of the substitution, the Z- or E-configuration is favorable for IPs, which in turn can influence the stereochemistry of the products of chemical transformations of IPs. While the Z,E-isomerism in IPs has been thoroughly studied by NMR spectroscopy, the factors stabilizing a definite isomer are still not clear. In the current work, density functional theory (DFT, using M06-2X functional) and ab initio spin-component–scaled second-order Møller–Plesset perturbation theory (SCS-MP2) calculations were carried out for a broad series of IPs. The calculations reproduce well a subtle balance between the preferred Z-configuration inherent for C-trifluoromethyl substituted IPs and the E-form, which is more stable for C-alkyl- or aryl-substituted IPs. The predicted trend of changing activation energy values agrees well with the recently determined experimental ΔG≠298 magnitudes. Depending on the substitution in the aromatic moiety, the Z/E-isomerization of N-aryl-substituted IPs proceeds via two types of close-in energy transition states. Not a single main factor but a combination of various contributions should be considered in order to explain the Z/E-isomerization equilibrium for different IPs.
Exposure to Major Vector-Borne Diseases in Dogs Subjected to Different Preventative Regimens in Endemic Areas of Italy
Authors: Colombo Mariasole , Morelli Simone , Simonato Giulia , Di Cesare Angela , Veronesi Fabrizia , Frangipane di Regalbono Antonio , Grassi Laura , Russi Ilaria , Tiscar Pietro Giorgio , Morganti Giulia , Hattab Jasmine , Rizzo Valeria , Traversa Donato
Published: April 2021

Vector-borne diseases (VBDs) are globally widespread arthropod-transmitted diseases with a significant impact on animal and human health. Many drivers have recently spurred the geographic spread of VBDs in dogs. This study has evaluated the exposure to most important VBDs in dogs under different preventative treatments in different regions of Italy, i.e., Veneto, Friuli Venezia-Giulia, Umbria, Giglio Island (Tuscany), Abruzzo and Latium. Serological analyses were performed to detect antibodies against Leishmania infantum, Babesia canis, Anaplasma phagocytophilum/Anaplasma platys, Ehrlichia canis/Ehrlichia ewingii, Borrelia burgdorferi, Rickettsia conorii and the circulating antigen of Dirofilaria immitis. Dogs were categorized according to the treatment schedule usually received, and the association between seropositivity and possible risk factors was statistically evaluated. Overall, 124/242 (51.2%) dogs tested positive for at least one pathogen, while 34 (14.0%) were exposed to two or more pathogens. The most detected seropositivity was against R. conorii, followed by Anaplasma spp., L. infantum, B. canis, and the other pathogens under study. Significant statistical associations were found according to geographical provenance, history of tick infestation, lifestyle and inadequate prophylactic treatments. Random/irregular treatments have been identified as a clear risk factor. These results show that adequate prophylactic treatment protocols are overlooked by dog owners, despite the availability of several effective products, with possible implications in veterinary medicine and on public health.
In Vitro Susceptibility of Multi-Drug Resistant Klebsiellapneumoniae Strains Causing Nosocomial Infections to Fosfomycin. A Comparison of Determination Methods
Authors: Mączyńska Beata , Paleczny Justyna , Oleksy-Wawrzyniak Monika , Choroszy-Król Irena , Bartoszewicz Marzenna
Published: April 2021

Introduction: Over the past few decades, Klebsiella pneumoniae strains increased their pathogenicity and antibiotic resistance, thereby becoming a major therapeutic challenge. One of the few available therapeutic options seems to be intravenous fosfomycin. Unfortunately, the determination of sensitivity to fosfomycin performed in hospital laboratories can pose a significant problem. Therefore, the aim of the present research was to evaluate the activity of fosfomycin against clinical, multidrug-resistant Klebsiella pneumoniae strains isolated from nosocomial infections between 2011 and 2020, as well as to evaluate the methods routinely used in hospital laboratories to assess bacterial susceptibility to this antibiotic. Materials and Methods: 43 multidrug-resistant Klebsiella strains isolates from various infections were tested. All the strains had ESBL enzymes, and 20 also showed the presence of carbapenemases. Susceptibility was determined using the diffusion method (E-test) and the automated system (Phoenix), which were compared with the reference method (agar dilution). Results: For the reference method and for the E-test, the percentage of strains sensitive to fosfomycin was 65%. For the Phoenix system, the percentage of susceptible strains was slightly higher and stood at 72%. The percentage of fosfomycin-resistant strains in the Klebsiella carbapenemase-producing group was higher (45% for the reference method and E-test and 40% for the Phoenix method) than in carbapenemase-negative strains (25%, 25%, and 20%, respectively). Full (100%) susceptibility categorical agreement was achieved for the E-test and the reference method. Agreement between the automated Phoenix system and the reference method reached 86%. Conclusions: Fosfomycin appears to be the antibiotic with a potential for use in the treatment of infections with multidrug-resistant Klebsiella strains. Susceptibility to this drug is exhibited by some strains, which are resistant to colistin and carbapenems. The E-test, unlike the Phoenix method, can be an alternative to the reference method in the routine determination of fosfomycin susceptibility, as it shows agreement in terms of sensitivity categories and only slight differences in MIC values. The Phoenix system, in comparison to the reference method, shows large discrepancies in the MIC values and in the susceptibility category.
Further Characterization of Glycoform-Selective Prions of Variably Protease-Sensitive Prionopathy
Authors: Zhang Weiguanliu , Xiao Xiangzhu , Ding Mingxuan , Yuan Jue , Foutz Aaron , Moudjou Mohammed , Kitamoto Tetsuyuki , Langeveld Jan P. M. , Cui Li , Zou Wen-Quan
Published: April 2021

Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD.
Microscopic Observation of SARS-Like Particles in RT-qPCR SARS-CoV-2 Positive Sewage Samples
Authors: Brahim Belhaouari Djamal , Wurtz Nathalie , Grimaldier Clio , Lacoste Alexandre , Pires de Souza Gabriel Augusto , Penant Gwilherm , Hannat Sihem , Baudoin Jean-Pierre , La Scola Bernard
Published: April 2021

The ongoing outbreak of novel coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection has spread rapidly worldwide. The major transmission routes of SARS-CoV-2 are recognised as inhalation of aerosol/droplets and person-to-person contact. However, some studies have demonstrated that live SARS-CoV-2 can be isolated from the faeces and urine of infected patients, which can then enter the wastewater system. The currently available evidence indicates that the viral RNA present in wastewater may become a potential source of epidemiological data. However, to investigate whether wastewater may present a risk to humans such as sewage workers, we investigated whether intact particles of SARS-CoV-2 were observable and whether it was possible to isolate the virus in wastewater. Using a correlative strategy of light microscopy and electron microscopy (CLEM), we demonstrated the presence of intact and degraded SARS-like particles in RT-qPCR SARS-CoV-2-positive sewage sample collected in the city of Marseille. However, the viral infectivity assessment of SARS-CoV-2 in the wastewater was inconclusive, due to the presence of other viruses known to be highly resistant in the environment such as enteroviruses, rhinoviruses, and adenoviruses. Although the survival and the infectious risk of SARS-CoV-2 in wastewater cannot be excluded from our study, additional work may be required to investigate the stability, viability, fate, and decay mechanisms of SARS-CoV-2 thoroughly in wastewater.
Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children
Authors: Druszczynska Magdalena , Seweryn Michal , Wawrocki Sebastian , Kowalewska-Pietrzak Magdalena , Pankowska Anna , Rudnicka Wieslawa
Published: April 2021

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.
Diurnal Variation of Plasma Extracellular Vesicle Is Disrupted in People Living with HIV
Authors: Bazié Wilfried Wenceslas , Goyer Benjamin , Boucher Julien , Zhang Yuwei , Planas Delphine , Chatterjee Debashree , Routy Jean-Pierre , Alary Michel , Ancuta Petronela , Gilbert Caroline
Published: April 2021

Background: Several types of extracellular vesicles (EVs) secreted by various immune and non-immune cells are present in the human plasma. We previously demonstrated that EV abundance and microRNA content change in pathological conditions, such as HIV infection. Here, we investigated daily variations of large and small EVs, in terms of abundance and microRNA contents in people living with HIV (PLWH) receiving antiretroviral therapy (HIV+ART) and uninfected controls (HIV−). Methods: Venous blood samples from n = 10 HIV+ART and n = 10 HIV− participants were collected at 10:00 and 22:00 the same day. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-29b, miR-92, miR-155, and miR-223 copies were measured by RT-PCR. Results: Large EVs were significantly bigger in the plasma collected at 10:00 versus 22:00 in both groups. There was a significant day–night increase in the quantity of 5 miRNAs in HIV− large EVs. In HIV+ART, only miR-155 daily variation has been observed in large EVs. Finally, EV-miRNA content permits to distinguish HIV− to HIV+ART in multivariate analysis. Conclusion: These results point that plasma EV amount and microRNA contents are under daily variation in HIV− people. This new dynamic measure is disrupted in PLWH despite viral-suppressive ART. This study highlights a significant difference concerning EV abundance and their content measured at 22:00 between both groups. Therefore, the time of blood collection must be considered in the future for the EV as biomarkers.