bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Highly Sensitive Anti-Mouse HER2 Monoclonal Antibodies for Flow Cytometry
Authors: Ouchida Tsunenori , Suzuki Hiroyuki , Tanaka Tomohiro , Kaneko Mika K. , Kato Yukinari
Published: August 2023

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab–deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate the developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed anti-mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) via flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) values of H2Mab-300 and H2Mab-304 for CHO/mHER2 were 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD values of H2Mab-300 and H2Mab-304 for NMuMG were 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.
Study on the Liquid Cooling Method of Longitudinal Flow through Cell Gaps Applied to Cylindrical Close-Packed Battery
Authors: Li Wei , Shi Wei , Xiong Shusheng , Huang Hai , Chen Guodong
Published: August 2023

The increasing popularity of electric vehicles presents both opportunities and challenges for the advancement of lithium battery technology. A new longitudinal-flow heat dissipation theory for cylindrical batteries is proposed in order to increase the energy density and uniform temperature performance of cylindrical lithium-ion battery packs while also shrinking their size by roughly 10%. First, a genetic algorithm is used to identify a single cell’s thermal properties. Based on this, modeling and simulation are used to examine the thermal properties of the longitudinal-flow-cooled battery pack. It is found that the best coolant flow scheme has one inlet and one outlet from the end face, taking into account the cooling effect of the battery pack and engineering viability. Lastly, thermal dummy cells (TDCs) are used to conduct a validation test of the liquid cooling strategy. Additionally, the simulation and test results demonstrate that the liquid cooling solution can restrict the battery pack’s maximum temperature rise under the static conditions of a continuous, high-current discharge at a rate of 3C to 20 °C and under the dynamic conditions of the New European Driving Cycle (NEDC) to 2 °C. In applications where the space requirements for the battery pack are quite strict, the longitudinal-flow cooling method has some advantages.
In-Vitro Comparison of Fracture Strength of Endocrowns and Overlays in Endodontically Treated Teeth Manufactured with Monolithic Lithium Disilicate and Zirconia
Authors: Veselinova Maya , Diamantopoulou Sofia , Paximada Chariklia , Papazoglou Efstratios
Published: August 2023

To evaluate the fracture strength and the failure mode of endodontically treated molars restored with monolithic lithium disilicate and zirconia endocrowns and overlays. A total of 48 extracted mandibular molars were endodontically treated, decoronated 2 mm above the cementoenamel junction and divided into four 12-specimen groups. Group ELD: lithium disilicate endocrowns. Group EZ: monolithic zirconia endocrowns. Group OLD: lithium disilicate overlays. Group OZ: monolithic zirconia overlays. Overlays did not extend in the pulp chamber and endocrowns extended in the pulp chamber 2 mm. After adhesive bonding of the restorations, the specimens were subjected to thermocycling (×5000 cycles) and then to fracture resistance testing at lateral static loading (1 mm/min) at a universal testing machine. The failure mode of the specimens was qualitatively evaluated. Differences in means were compared using with t-tests for independent samples or Mann–Whitney test (p < 0.05). Weibull distribution analysis was also performed. Group ELD showed significantly higher fracture strength than all other groups (p = 0.001), and the highest Weibull modulus. Conclusions: Lithium disilicate endocrowns exhibit higher fracture strength and are more reliable compared to the other types of restorations examined. Endocrowns had more catastrophic failures compared to overlays.
Nanotheranostics: Platforms, Current Applications, and Mechanisms of Targeting in Breast and Prostate Cancers
Authors: Akpa Paul A. , Peter Ikechukwu E. , Onwuka Akachukwu M. , Obi Bonaventure C. , Akunne Maureen O. , Nworu Chukwuemeka S. , Ejikeme Paul M. , Akunne Theophine C. , Attama Anthony A. , Akah Peter A.
Published: August 2023

Globally, cancer is one of the deadliest diseases, needing a meticulous diagnosis and targeted treatment plan to achieve an initial prognosis, followed by precision and optimization in treatment. Nonselective targeting, difficulty in accurately monitoring treatment end-results, serious drug side-effects, and severity of disease resulting in metastasis are the key flaws of traditional techniques. Nanotechnology and nanoparticles possess special features to completely transform the field of diagnosis and treatment of cancer. A holistic strategy that employs a dual function of diagnosis and therapy while utilizing a nanocarrier is referred to as a nanotheranostic. The nanotheranostic framework was created to surmount a variety of biological and physiological obstacles, effectively delivering the cargo to the intended target location, while simultaneously facilitating therapeutic intervention, surveillance, and validation to demonstrate improved treatment effectiveness. As a result, a nanotheranostic platform can be useful for targeted drug delivery, release, and distribution assessment, in addition to patient classification and survival. Nanotheranostic techniques also lead to reduced drug side-effects compared with conventional therapies. In this review, we outline current studies on nanotheranostics and their advantages over conventional treatment strategies, the applications and challenges/limitations of nanotheranostics, and the mechanisms of targeting in breast and prostate cancers.
Smart Platinum Nanostructures: A Journey from Synthesis to Advanced Theranostic Applications
Authors: Kumar Akash , Das Nabojit , Rayavarapu Raja Gopal
Published: August 2023

A significant paradigm shift has been observed in the past decade in the area of theranostics owing to the development of various isotropic and anisotropic metal nanostructures, simultaneous with improved imaging modalities. Platinum-based nanostructures are advancing in a plethora of clinical applications as theranostics tools owing to their unique behavior concerning their size, shape, and surface chemistry at the nanoscale regime. Platinum nanostructures are optically active and provide significant potential to the field of theranostics by simplifying diagnosis and therapeutics, thus providing key solutions through nano-enabled technologies. The review emphasizes the potential of platinum nanostructures that have immense potential in vitro and in vivo scenarios as nanocarriers. Still, their potential in terms of photothermal active agents has not been well explored or reported. Nanotheranostics has emerged as a platform where various noble metal nanoparticles are effectively efficient as photothermal agents in bringing precision to therapy and diagnostics. Platinum, as an antioxidant and a stable nanocarrier, will enable them to act as photosensitizers when conjugated to affinity molecules and plays a key role in efficient treatment and diagnosis. The review envisions bringing together the possibilities of the safe-by-design synthesis of platinum nanostructures and their potential role in both in vitro and in vivo applications. A roadmap describing the challenges, pitfalls, and possibilities of influencing platinum nanostructures to overcome the existing biological/targeting barriers is elaborated. This review provides a literature survey on platinum nanostructures in theranostics, providing novel strategies in bio-imaging, diagnostics, and nanomedicine.
Tensors Associated with Mean Quadratic Differences Explaining the Riskiness of Portfolios of Financial Assets
Authors: Angelini Pierpaolo , Maturo Fabrizio
Published: August 2023

Bound choices such as portfolio choices are studied in an aggregate fashion using an extension of the notion of barycenter of masses. This paper answers the question of whether such an extension is a natural fashion of studying bound choices or not. Given n risky assets, the question of why it is appropriate to treat only two risky assets at a time inside the budget set of the decision-maker is handled in this paper. Two risky assets are two goods. They are two marginal goods. The question of why they always give rise to a joint good inside the budget set of the decision-maker is addressed by this research work. A single risky asset is viewed as a double one using four nonparametric joint distributions of probability. The variability of a joint distribution of probability always depends on the state of information and knowledge associated with a given decision-maker. For this reason, two variability tensors are defined to identify the riskiness of the same risky asset. A multilinear version of the Sharpe ratio is shown. It is based on tensors. After computing the expected return on an n-risky asset portfolio, its riskiness is obtained using mean quadratic differences developed through tensors.
The Effects of the Combination of Rhein and Platelet-Rich Plasma on Human Articular Chondrocytes
Authors: Simental-Mendía Mario , Lozano-Sepúlveda Sonia Amelia , Garza-Tapia Marsela , Lara-Arias Jorge , Acosta-Olivo Carlos Alberto , Vilchez-Cavazos Félix , Peña-Martínez Víctor Manuel
Published: August 2023

Background: The presence of side effects and low bioavailability of rhein has limited its use in the treatment of osteoarthritis. We aimed to evaluate the in vitro response of human articular chondrocytes to the presence of the combination of platelet-rich plasma (PRP) and rhein. Methods: Solutions of rhein were prepared to assess solubility and select a working concentration. A stimulus with interleukin-1β (IL-β, 10 ng/mL) was induced for 24 h on human chondrocytes. Five treatment groups were established: control, IL-β control, PRP, rhein, and PRP + rhein. Cell viability, cell migration, nitric oxide (NO) production, tumor necrosis factor-α (TNF-α), and gene expression analyses were carried out. Results: A concentration of 50 mg/L was selected after a dose–response curve assay. Both NO and tumor TNF-α production significantly decreased after PRP and PRP + rhein treatments at 24 and 48 h. The wound healing assay revealed a significant stimulation of migration after 72 h with the PRP and PRP + rhein treatments. Expression of IL-1β, IL-6, MMP-13, and ADAMTS-5 was significantly downregulated, particularly after treatment with the combination of PRP + rhein. Conclusions: Much of the determinations denoted a better performance of the combination of PRP and rhein in decreasing the levels of the different targets evaluated; however, this was not great enough to detect a significant difference in comparison with the PRP treatment alone.
Gastroenterological Manifestations of Immunoglobulin G Subclass 4-Related Disease—Epidemiology, Clinical Manifestations, Diagnosis and Treatment
Authors: Moreira Jorge Lucas de Sousa , Barbosa Sarah Maria Bacurau , Meneses Pedro Lucas Gomes Moreira de , Barros Pedro Garcia Dias de , Lima Samuel de Sá Barreto , Gomes Junior Damiao Maroto , Leite Gledson Micael da Silva , Duarte Jacob Oliveira , Alencar Junior Galba Matos Cardoso de , Almino Maria Auxiliadora Ferreira Brito , Cruz José Matos , Batista Hermes Melo Teixeira , Cândido Estelita Lima , Oliveira Gislene Farias de , Cruz Hellen Lúcia Macedo , Gonçalves Júnior Jucier
Published: August 2023

Despite causing high morbidity, IgG4-related disease (IgG4-RD) and its gastroenterological manifestations lack better and greater theoretical contributions. Therefore, the objective of this work was to evaluate the clinical–epidemiological, diagnostic and treatment aspects of the gastrointestinal manifestations of this disease. A systematic review was carried out using the PubMed, Scopus and Embase databases between January 2012 and March 2023 with the following descriptors: “Immunoglobulin G4-Related Disease” (MeSH) AND #2 “Gastrointestinal Tract” (MeSH). Our data collection grouped a total of 3607 patients from mostly epidemiological cohort studies and cross-sectional follow-ups. In the subgroup analysis, IgG4-RD was associated with male gender, with an estimated prevalence between 54% and 80%. In our findings, the prevalence by topography was presented in the following ranges: lacrimal glands (17–57%); salivary glands (28–72%); pancreas (19–60%); biliary tract (5–40%); retroperitoneal cavity (9–43%). Longitudinal studies are needed to better map the natural history of the gastrointestinal manifestations of IgG4-RD and enable the formulation of individualized treatments.
Thermodynamic and Ab Initio Design of Multicomponent Alloys Based on (Fe50Mn30Co10Cr10)-xBx (x = 0, 5, 7, 10, and 15 at.%)
Authors: Vargas-Osorio Rodrigo , Torres-Mejia Laura Gabriela , Mujica-Roncery Lais , Aguilar-Hurtado Jose Y. , Paredes-Gil Katherine
Published: August 2023

Multicomponent alloys have attained general interest in recent years due to their remarkable performance. Non-equiatomic alloys with boron addition as an interstitial element are being studied, exhibiting outstanding mechanical properties. In order to estimate the mechanical behavior of potential alloys, thermodynamic and ab initio calculations were utilized in this work to investigate phase stability and stacking fault energy (SFE) for (Fe50Mn30Co10Cr10)-xBx (x = 0, 5, 7, 10, and 15 at.%) systems. Thermodynamic experiments revealed two structural variations of borides, M2B(C16) with a tetragonal structure and M2B(CB) with an orthorhombic structure. Borides precipitate when boron content increases, and the FCC matrix becomes deficient in Mn and Cr. According to ab initio calculations, the presence of boron in the FCC and HCP structures primarily disrupts the surroundings of the Fe and Mn atoms, resulting in an increased distortion of the crystal lattice. This is related to the antiferromagnetic condition of the alloys. Furthermore, for alloys with a low boron concentration, the stacking fault energy was found to be near 20 mJ/m2 and greater than 50 mJ/m2 when 10 and 15 at.% boron was added. As boron concentrations increase, M2B borides are formed, generating changes in the matrix composition prone to fault-induced phase transitions that could modify and potentially impair mechanical properties.
Coloring Effects of Disinfectants on Pure or Nano-TiO2-Incorporated Maxillofacial Silicone Prostheses
Authors: Cevik Pinar
Published: August 2023

Silicone elastomers play a crucial role in the field of maxillofacial prosthodontics. To maintain optimal hygiene, various disinfectants have been reported to clean silicone prostheses. Nevertheless, when selecting a disinfectant, it is important to consider not only its antimicrobial efficacy, but also its compatibility with the materials, to minimize any potential impact on the physical properties of the material surfaces. The coloring effect of such disinfectants on different types of silicone is of interest. A total of 144 silicone specimens (72 pure silicones, 72 nano-TiO2-incorporated silicones, from A-2000 and A-2006 silicones) were fabricated in this study. The spectrophotometric analysis was carried out, and the initial CIE L*a*b* color values were measured prior to disinfection. Specimens in each silicone group (with or without nano-TiO2) were subjected to a 30-h disinfection period simulating 1 year of disinfection with the following disinfectants: Control (tap water), 0.2% chlorhexidine gluconate, 4% chlorhexidine gluconate, 1% NaOCl, neutral soap, and effervescent. After the second color values were recorded, the color change (∆E*) was calculated. Significant differences were observed among the disinfectants for both the A-2000 and A-2006 silicone groups. Nano-TiO2 did not show a color protection effect in A-2000 silicone. In contrast, nano-TiO2 incorporation provided color protection against CHG 0.2%, CHG 4%, and NaOCl in A-2006 silicone. Most of the disinfectants did not show acceptable color stability over time. In pure A-2000 silicone, except for 0.2% chlorhexidine, all disinfectant groups demonstrated a color change within the acceptability threshold of 50:50% (∆E* = 3.0). On the other hand, in nano-TiO2-incorporated A-2006 silicone, only 0.2% and 4% chlorhexidine demonstrated an acceptable color change. Overall, chlorhexidine could be used as a suitable disinfectant in maxillofacial silicone prostheses.
Optical Filters with Asymmetric Transmittance Depending on the Incident Angle, Produced Using Liquid Crystalline Ink (Louver LC Filters)
Authors: Takatoh Kohki , Kobayashi Mika , Ito Masahiro
Published: August 2023

In many situations in everyday life, sunlight levels need to be reduced. Optical filters with asymmetric transmittance dependent on the incident angle would be useful for sunglasses and vehicle or architectural windows, among others. Herein, we realized the production of optical filters, called “louver filters”, comprising HAN-type LC film produced using liquid crystalline ink with dichroic dyes. For the formation of the HAN-type LC film, the liquid crystalline ink was aligned on a rubbed polyimide layer and polymerized by UV irradiation. Two kinds of filters are proposed: one is a filter composed of HAN-type LC film and a polarizer, and the other is composed of two HAN-LC films with a half-wave plate between them. The dependence of the asymmetric transmittance on the incident angle was confirmed for these filters. The dependence changed depending on the pretilt angle of the alignment layers. Photographs taken with the optical filters displayed their effectiveness.
DSC Investigation and Thermodynamic Modeling of the Al–Sb–Sn System
Authors: Wei Wenjie , Chen Wei , Wang Yaping , Cao Zhanmin
Published: August 2023

The Al–Sb–Sn ternary system was studied by combining experimental measurement and thermodynamic modeling. The three vertical cross-sections of Al–SnSb, Sn–AlSb, and Sb–AlSn were measured by Differential Scanning Calorimetry (DSC). Based on the Calculation of Phase Diagram (CALPHAD) method, the thermodynamic modeling of the Al–Sb–Sn ternary system was carried out based on the evaluated experimental data by FactSage. A set of thermodynamic model parameters consistent with the experimental data was obtained.
The Influence of Liquid/Solid Ratio and Pressure on the Natural and Accelerated Carbonation of Alkaline Wastes
Authors: Sorrentino Giampiero Pasquale , Guimarães Renato , Valentim Bruno , Bontempi Elza
Published: August 2023

The purpose of this research is to assess the yield and reaction rate potential of carbon dioxide (CO2) sequestration through mineralisation using readily available and inexpensive resources by exploiting waste materials. In this case, a blend of four different kinds of ashes and combustion by-products were used, namely, coal fly ash (CFA), flue gas desulphurization (FGD) residues, municipal solid waste incineration fly ashes (MSWI FA) and bottom ash (MSWI BA), produced at the same location. To highlight the impact of these materials on the carbonation process, various factors were analysed, including particle size distribution, immediately soluble contents, mineralogy, particles’ detailed structure, and chemical composition. After preparing the samples, two carbonation processes were tested: natural carbonation and accelerated carbonation. To evaluate the impact of the water content on the reaction rate and yield of the mineral carbonation, various liquid-to-solid (L/S) ratios were used. The results demonstrate that the water content and pressure play a significant role in the CO2 sequestration during the accelerated carbonation, the higher the L/S, the greater the yields, which can reach up to 152 g CO2/kg with MSWI FA, while no substantial difference seems to emerge in the case of the natural carbonation.
Enhanced Oxygen Storage Capacity of Porous CeO2 by Rare Earth Doping
Authors: Xu Yaohui , Gao Liangjuan , Hou Quanhui , Wu Pingkeng , Zhou Yunxuan , Ding Zhao
Published: August 2023

CeO2 is an important rare earth (RE) oxide and has served as a typical oxygen storage material in practical applications. In the present study, the oxygen storage capacity (OSC) of CeO2 was enhanced by doping with other rare earth ions (RE, RE = Yb, Y, Sm and La). A series of Undoped and RE–doped CeO2 with different doping levels were synthesized using a solvothermal method following a subsequent calcination process, in which just Ce(NO3)3∙6H2O, RE(NO3)3∙nH2O, ethylene glycol and water were used as raw materials. Surprisingly, the Undoped CeO2 was proved to be a porous material with a multilayered special morphology without any additional templates in this work. The lattice parameters of CeO2 were refined by the least–squares method with highly pure NaCl as the internal standard for peak position calibrations, and the solubility limits of RE ions into CeO2 were determined; the amounts of reducible–reoxidizable Cen+ ions were estimated by fitting the Ce 3d core–levels XPS spectra; the non–stoichiometric oxygen vacancy (VO) defects of CeO2 were analyzed qualitatively and quantitatively by O 1s XPS fitting and Raman scattering; and the OSC was quantified by the amount of H2 consumption per gram of CeO2 based on hydrogen temperature programmed reduction (H2–TPR) measurements. The maximum [OSC] of CeO2 appeared at 5 mol.% Yb–, 4 mol.% Y–, 4 mol.% Sm– and 7 mol.% La–doping with the values of 0.444, 0.387, 0.352 and 0.380 mmol H2/g by an increase of 93.04, 68.26, 53.04 and 65.22%. Moreover, the dominant factor for promoting the OSC of RE–doped CeO2 was analyzed.
Untargeted Metabolomic Analysis Combined with Chemometrics Revealed the Effects of Different Cooking Methods on Lentinus edodes
Authors: Zhu Jinrui , Zhou Li , Yao Jiaxu , Hu Yueqi , Li Zhenghui , Liu Jikai , Marchioni Eric
Published: August 2023

Cooking methods affect the compositions of Lentinus edodes metabolites. Nevertheless, little information is available on the specific impact of different cooking methods on Lentinus edodes via metabolomic analysis. This study determined the influence of boiling, steaming, air-frying, and roasting on the metabolomic profiles of Lentinus edodes based on UHPLC-Q-Exactive Orbitrap MS/MS in combination with chemometrics. A total of 990 metabolites were detected and classified into 11 super-classes. Subsequently, the metabolites of the four cooking methods were distinguished using multivariate statistical analysis. The results showed that boiling caused a massive loss of metabolites while roasting and air-frying led to an evident upregulation. The upregulation of metabolites in the steaming groups was not as significant as in roasting and air-frying. This study provided reference data for a comprehensive understanding of the metabolites associated with domestic cooking methods and valuable guidance for the development of Lentinus edodes and its products in the future.
Virtual Screening of Different Subclasses of Lignans with Anticancer Potential and Based on Genetic Profile
Authors: Maia Mayara dos Santos , Mendonça-Junior Francisco Jaime Bezerra , Rodrigues Gabriela Cristina Soares , Silva Adriano Soares da , Oliveira Niara Isis Pereira de , Silva Pablo Rayff da , Felipe Cícero Francisco Bezerra , Gurgel Ana Pavla Almeida Diniz , Nayarisseri Anuraj , Scotti Marcus Tullius , Scotti Luciana
Published: August 2023

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. To do so, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epidermal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), serine/threonine-protein kinase mTOR (mTOR) and poly [ADP-ribose] polymerase-1 (PARP1). Then, single nucleotide polymorphisms were mapped, target mutations were designed, and molecular docking was performed with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.
Functional and Bioactive Properties of Wheat Protein Fractions: Impact of Digestive Enzymes on Antioxidant, α-Amylase, and Angiotensin-Converting Enzyme Inhibition Potential
Authors: Gammoh Sana , Alu’datt Muhammad H. , Alhamad Mohammad N. , Tranchant Carole C. , Rababah Taha , Al-U’datt Doa’a , Hussein Neveen , Alrosan Mohammad , Tan Thuan-Chew , Kubow Stan , Alzoubi Haya , Almajwal Ali
Published: August 2023

This research aimed to determine the biofunctional properties of wheat flour (WF) protein fractions and modifications to the antioxidant, anti-α-amylase and anti-angiotensin-I converting enzyme (ACE) activities induced by the action of digestive endopeptidases in vitro. A molecular characterization of the most abundant protein fractions, i.e., albumins, glutelins-1, glutelins-2 and prolamins, showed that low- and high-MW polypeptides rich in cysteine, glutamic acid and leucine were present in albumins and glutelins, whereas low-MW subunits with a high proportion of polar amino acids prevailed in prolamins. Prolamins exhibited the second-highest water holding capacity (54%) after WF (84%), while albumins provided superior foam stability (76%). Prolamins, glutenins-1 and globulins demonstrated the highest antioxidant activity (up to 95%, 68% and 59%, respectively) both before and after hydrolysis with pepsin (P-H) or trypsin–chymotrypsin (TC-H). Prolamins, globulins and WF strongly inhibited α-amylase (>90%) before and after TC-H, and before P-H (55–71%). Moreover, P-H significantly increased α-amylase inhibition by albumins from 53 to 74%. The fractions with strong ACE inhibitory activity (70–89%) included prolamins and globulins after TC-H or P-H, as well as globulins before TC-H and WF before P-H. This novel evidence indicates that WF protein fractions and their peptide-enriched P and TC hydrolysates are excellent sources of multifunctional bioactives with antioxidant, antihyperglycemic and antihypertensive potential.
A New Perspective for the Treatment of Alzheimer’s Disease: Exosome-like Liposomes to Deliver Natural Compounds and RNA Therapies
Authors: Ribeiro Joana , Lopes Ivo , Gomes Andreia Castro
Published: August 2023

With the increment of the aging population in recent years, neurodegenerative diseases exert a major global disease burden, essentially as a result of the lack of treatments that stop the disease progression. Alzheimer’s Disease (AD) is an example of a neurodegenerative disease that affects millions of people globally, with no effective treatment. Natural compounds have emerged as a viable therapy to fill a huge gap in AD management, and in recent years, mostly fueled by the COVID-19 pandemic, RNA-based therapeutics have become a hot topic in the treatment of several diseases. Treatments of AD face significant limitations due to the complex and interconnected pathways that lead to their hallmarks and also due to the necessity to cross the blood–brain barrier. Nanotechnology has contributed to surpassing this bottleneck in the treatment of AD by promoting safe and enhanced drug delivery to the brain. In particular, exosome-like nanoparticles, a hybrid delivery system combining exosomes and liposomes’ advantageous features, are demonstrating great potential in the treatment of central nervous system diseases.
Assessing the Performance of Non-Equilibrium Thermodynamic Integration in Flavodoxin Redox Potential Estimation
Authors: Silvestri Giuseppe , Arrigoni Federica , Persico Francesca , Bertini Luca , Zampella Giuseppe , De Gioia Luca , Vertemara Jacopo
Published: August 2023

Flavodoxins are enzymes that contain the redox-active flavin mononucleotide (FMN) cofactor and play a crucial role in numerous biological processes, including energy conversion and electron transfer. Since the redox characteristics of flavodoxins are significantly impacted by the molecular environment of the FMN cofactor, the evaluation of the interplay between the redox properties of the flavin cofactor and its molecular surroundings in flavoproteins is a critical area of investigation for both fundamental research and technological advancements, as the electrochemical tuning of flavoproteins is necessary for optimal interaction with redox acceptor or donor molecules. In order to facilitate the rational design of biomolecular devices, it is imperative to have access to computational tools that can accurately predict the redox potential of both natural and artificial flavoproteins. In this study, we have investigated the feasibility of using non-equilibrium thermodynamic integration protocols to reliably predict the redox potential of flavodoxins. Using as a test set the wild-type flavodoxin from Clostridium Beijerinckii and eight experimentally characterized single-point mutants, we have computed their redox potential. Our results show that 75% (6 out of 8) of the calculated reaction free energies are within 1 kcal/mol of the experimental values, and none exceed an error of 2 kcal/mol, confirming that non-equilibrium thermodynamic integration is a trustworthy tool for the quantitative estimation of the redox potential of this biologically and technologically significant class of enzymes.
Fluoroquinolone Analogs, SAR Analysis, and the Antimicrobial Evaluation of 7-Benzimidazol-1-yl-fluoroquinolone in In Vitro, In Silico, and In Vivo Models
Authors: Medellín-Luna Mitzzy Fátima , Hernández-López Hiram , Castañeda-Delgado Julio Enrique , Martinez-Gutierrez Fidel , Lara-Ramírez Edgar , Espinoza-Rodríguez Joan Jair , García-Cruz Salvador , Portales-Pérez Diana Patricia , Cervantes-Villagrana Alberto Rafael
Published: August 2023

Structure–activity relationship (SAR) studies allow the evaluation of the relationship between structural chemical changes and biological activity. Fluoroquinolones have chemical characteristics that allow their structure to be modified and new analogs with different therapeutic properties to be generated. The objective of this research is to identify and select the C-7 heterocycle fluoroquinolone analog (FQH 1–5) with antibacterial activity similar to the reference fluoroquinolone through in vitro, in silico, and in vivo evaluations. First, SAR analysis was conducted on the FQH 1–5, using an in vitro antimicrobial sensibility model in order to select the best compound. Then, an in silico model mechanism of action analysis was carried out by molecular docking. The non-bacterial cell cytotoxicity was evaluated, and finally, the antimicrobial potential was determined by an in vivo model of topical infection in mice. The results showed antimicrobial differences between the FQH 1–5 and Gram-positive and Gram-negative bacteria, identifying the 7-benzimidazol-1-yl-fluoroquinolone (FQH-2) as the most active against S. aureus. Suggesting the same mechanism of action as the other fluoroquinolones; no cytotoxic effects on non-bacterial cells were found. FQH-2 was demonstrated to decrease the amount of bacteria in infected wound tissue.
Aloe-Emodin Overcomes Anti-Cancer Drug Resistance to Temozolomide and Prevents Colony Formation and Migration in Primary Human Glioblastoma Cell Lines NULU and ZAR
Authors: Staffieri Sabrina , Russo Veronica , Oliva Maria Antonietta , Alborghetti Marika , Russo Miriam , Arcella Antonietta
Published: August 2023

Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a significant additive inhibitory effect on cell growth and a promising cytotoxic effect on both cell lines compared to treatment with single agents. We also examined the effect of combined AE and TMZ treatment on the drug-resistance protein MGMT. The results suggest that using AE combined with traditional drugs restores drug resistance in both primary resistant cell lines (NULU and ZAR). Furthermore, migration assays and scratch tests showed that the combined use of AE and TMZ can slow down the colony formation and migration of glioblastoma cells. These convincing results suggest that AE could be a natural adjuvant agent to potentiate the effects of traditional drugs (TMZ) and overcome drug resistance in glioblastoma cells.
Microemulsions of Nonionic Surfactant with Water and Various Homologous Esters: Preparation, Phase Transitions, Physical Property Measurements, and Application for Extraction of Tricyclic Antidepressant Drugs from Aqueous Media
Authors: Racovita Radu C. , Ciuca Maria D. , Catana Daniela , Comanescu Cezar , Ciocirlan Oana
Published: August 2023

Microemulsions are nanocolloidal systems composed of water, an oil, and a surfactant, sometimes with an additional co-surfactant, which have found a wide range of practical applications, including the extractive removal of contaminants from polluted water. In this study, microemulsion systems, including a nonionic surfactant (Brij 30), water, and esters selected from two homologous series of C1–C6 alkyl acetates and ethyl C1–C4 carboxylates, respectively, were prepared by the surfactant titration method. Phase transitions leading to the formation of Winsor II and Winsor IV microemulsions were observed and phase diagrams were constructed. The dependences of phase transitions on the salinity and pH and the addition of isopropanol as a co-surfactant were also investigated. Some physical properties, namely density, refractive index, electrical conductivity, dynamic viscosity, and particle size, were measured for a selection of Winsor IV microemulsions, providing further insight into some other phase transitions occurring in the monophasic domains of phase diagrams. Finally, Winsor II microemulsions were tested as extraction solvents for the removal of four tricyclic antidepressant drugs from aqueous media. Propyl acetate/Brij 30/H2O microemulsions provided the best extraction yields (>90%), the highest Nernst distribution coefficients (~40–88), and a large volumetric ratio of almost 3 between the recovered purified water and the resulting microemulsion extract. Increasing the ionic strength (salinity) or the pH of the aqueous antidepressant solutions led to an improvement in extraction efficiencies, approaching 100%. These results could be extrapolated to other classes of pharmaceutical contaminants and suggest ester- and nonionic surfactant-based microemulsions are a promising tool for environmental remediation.
Protection of Inonotus hispidus (Bull.) P. Karst. against Chronic Alcohol-Induced Liver Injury in Mice via Its Relieving Inflammation Response
Authors: Jin Xinghui , Li Zhige , Zhang Yongfeng , Zhu Yanfeng , Su Ling , Song Jiyu , Hao Jie , Wang Di
Published: August 2023

Alcoholic liver disease (ALD) can be induced by excessive alcohol consumption, and has a worldwide age-standardized incidence rate (ASIR) of approximately 5.243%. Inonotus hispidus (Bull.) P. Karst. (IH) is a mushroom with pharmacological effects. In ALD mice, the hepatoprotective effects of IH were investigated. IH strongly ameliorated alcohol-induced pathological changes in the liver, including liver structures and its function-related indices. Intestinal microbiota and serum metabolomics analysis showed that IH altered the associated anti-inflammatory microbiota and metabolites. According to results obtained from Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA), IH downregulated the levels of pro-inflammation factors interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), enhanced the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and 15-hydroxprostaglandin dehydrogenase (15-PGDH), and inhibited the phosphorylated activation of Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3, confirming the hepatoprotection of IH against alcohol damage via anti-inflammation. This study provides the experimental evidence for the hepatoprotective effects of IH in chronic ALD.
Effects on Fetal Metabolic Programming and Endocannabinoid System of a Normocaloric Diet during Pregnancy and Lactation of Female Mice with Pregestational Obesity
Authors: Barrera Cynthia , Castillo Valeska , Valenzuela Rodrigo , Valenzuela Carina A. , Garcia-Diaz Diego F. , Llanos Miguel
Published: August 2023

Fetal programming provides explanatory mechanisms for the currently high prevalence of gestational obesity. The endocannabinoid system (ECS) participates in the regulation of energy balance, and with a high-fat diet (HFD), it is overactivated. The aim of this study was to determine the effects of a nutritional intervention during pregnancy and lactation on obese female progenitors, on metabolic alterations of the offspring and on the involvement of ECS. Female mice (C57/BL/6-F0), 45 days old, and their offspring (males) were separated according to type of diet before and during gestation and lactation: CON-F1: control diet; HFD-F1 group: HFD (fat: 60% Kcal); INT-F1 group: HFD until mating and control diet (fat: 10% Kcal) afterward. Glucose tolerance and insulin sensitivity (IS) were tested at 2 and 4 months. At 120 days, mice were sacrificed, plasma was extracted for the determination of hormones, and livers for gene expression and the protein level determination of ECS components. INT-F1 group presented a lower IS compared to CON-F1, and normal levels of adiponectin and corticosterone in relation to the HFD-F1 group. The intervention increased hepatic gene expression for fatty-acid amide hydrolase and monoacylglycerol lipase enzymes; however, these differences were not observed at the protein expression level. Our results suggest that this intervention model normalized some hormonal parameters and hepatic mRNA levels of ECS components that were altered in the offspring of progenitors with pre-pregnancy obesity.
Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Long-Term Results of a Prospective Phase II Study
Authors: Keizman Daniel , Frenkel Moshe , Peer Avivit , Rosenbaum Eli , Sarid David , Leibovitch Ilan , Mano Roy , Yossepowitch Ofer , Wolf Ido , Geva Ravit , Margel David , Rouvinov Keren , Stern Anat , Dresler Hadas , Kushnir Igal , Eliaz Isaac
Published: August 2023

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.
Whey Protein Dietary Supplements: Metal Exposure Assessment and Risk Characterization
Authors: Bethencourt-Barbuzano Elena , González-Weller Dailos , Paz-Montelongo Soraya , Gutiérrez-Fernández Ángel J. , Hardisson Arturo , Carrascosa Conrado , Cámara Montaña , Rubio-Armendáriz Carmen
Published: August 2023

Protein supplements (PS) are trendy foods, especially those made from whey. In addition to providing protein, these products are a source of metals, providing essential elements (Na, K, Mg, Ca, Mo, Mn, Fe, Co, Cu, and Zn) and other potentially toxic elements (Al, B, Sr, V Ba, and Ni). In this study, 47 whey PS samples were analyzed for mineral elements by ICP-OES, and their dietary exposures were assessed for three consumption scenarios. Elements found in higher concentrations were K (4689.10 mg/kg) and Ca (3811.27 mg/kg). The intake of 30 g PS (average recommended amount/day) provides about 20% of the established reference value (NRI) for Cr (18.30% for men and 25.63% for women) and Mo (26.99%). In a high daily consumption scenario (100 g PS/day) and when the maximum concentrations are considered, Cr, Zn, Fe, Mo, and Mg dietary intakes of these metals exceed the daily recommended intakes and could pose a risk. The daily intake of 30, 60, and 100 g of whey PS for 25 years does not pose a health risk since the hazard index (HI) is less than one in these consumption scenarios, and the essential elements contributing most to HI are Co, followed by Mo and Cr. It is recommended to improve the information to the consumers of these new products. Furthermore, to help in the management and prevention of these potential health risks, it would be advisable to improve the regulation of these dietary supplements and their labeling.
More Nutritional Support on the Wards after a Previous Intensive Care Unit Stay: A nutritionDay Analysis in 136,667 Patients
Authors: Fischer Arabella , Veraar Cecilia , Worf Isabella , Tarantino Silvia , Kiss Noemi , Schuh Christian , Hiesmayr Michael
Published: August 2023

ICU (intensive care unit) patients are exposed to nutritional risks such as swallowing problems and delayed gastric emptying. A previous ICU stay may affect nutritional support upon transfer to the ward. The aim was to study the use of enteral (EN), parenteral nutrition (PN), and oral nutritional supplements (ONS) in ward patients with and without a previous ICU stay, also referred to as post- and non-ICU patients. In total, 136,667 adult patients from the nutritionDay audit 2010–2019 were included. A previous ICU stay was defined as an ICU stay during the current hospitalisation before nutritionDay. About 10% of all patients were post-ICU patients. Post-ICU patients were more frequently exposed to risk factors such as a BMI < 18.5 kg/m2, weight loss, decreased mobility, fair or poor health status, less eating and a longer hospital length of stay before nDay. Two main results were shown. First, both post- and non-ICU patients were inadequately fed: About two thirds of patients eating less than half a meal did not receive EN, PN, or ONS. Second, post-ICU patients had a 1.3 to 2.0 higher chance to receive EN, PN, or ONS compared to non-ICU patients in multivariable models, accounting for sex, age, BMI, weight change, mobility, health status, amount eaten on nutritionDay, hospital length of stay, and surgical status. Based on these results, two future goals are suggested to improve nutritional support on the ward: first, insufficient eating should trigger nutritional therapy in both post- and non-ICU patients; second, medical caregivers should not neglect nutritional support in non-ICU patients.
Poultry Consumption and Human Cardiometabolic Health-Related Outcomes: A Narrative Review
Authors: Connolly Gavin , Campbell Wayne W.
Published: August 2023

Poultry meats, in particular chicken, have high rates of consumption globally. Poultry is the most consumed type of meat in the United States (US), with chicken being the most common type of poultry consumed. The amounts of chicken and total poultry consumed in the US have more than tripled over the last six decades. This narrative review describes nutritional profiles of commonly consumed chicken/poultry products, consumption trends, and dietary recommendations in the US. Overviews of the scientific literature pertaining to associations between, and effects of consuming chicken/poultry on, body weight and body composition, cardiovascular disease (CVD), and type II diabetes mellitus (T2DM) are provided. Limited evidence from randomized controlled trials indicates the consumption of lean unprocessed chicken as a primary dietary protein source has either beneficial or neutral effects on body weight and body composition and risk factors for CVD and T2DM. Apparently, zero randomized controlled feeding trials have specifically assessed the effects of consuming processed chicken/poultry on these health outcomes. Evidence from observational studies is less consistent, likely due to confounding factors such as a lack of a description of and distinctions among types of chicken/poultry products, amounts consumed, and cooking and preservation methods. New experimental and observational research on the impacts of consuming chicken/poultry, especially processed versions, on cardiometabolic health is sorely needed.
Serum Iodine as a Potential Individual Iodine Status Biomarker: A Cohort Study of Mild Iodine Deficient Pregnant Women in China
Authors: Li Xueqing , Tu Pengcheng , Gu Simeng , Mo Zhe , Wu Lizhi , Xing Mingluan , Chen Zhijian , Wang Xiaofeng
Published: August 2023

Iodine deficiency during pregnancy is a widespread public health concern, but indicators and methods for assessing iodine nutritional status are lacking. Serum iodine concentration (SIC) is an important iodine metabolism biomarker and can, to some extent, predict the risk of thyroid diseases, making it a potential biomarker for assessing individual iodine nutrition levels. Our study aimed to analyze the relationship between SIC and thyroid function in a cohort of mild iodine deficient pregnant women in China in order to explore the potential of SIC as a biomarker of individual iodine status in pregnancy. A total of 1540 early pregnant women (gestation < 10 weeks) aged 18 to 45 years old were included in the final study from a Zhejiang multicenter population-based mother and child cohort. Repeated measures of SIC, urinary iodine concentration (UIC), and thyroid function were taken at approximately 10, 17, and 32 weeks of gestation. The SIC was statistically correlated with all thyroid function indexes in the first trimester, and a very strong positive correlation with FT4 over three trimesters (r = 0.449, 0.550, and 0.544, respectively). Pregnant women with an SIC < 72.4 µg/L were at a higher risk of hypothyroxinemia (adjusted OR = 8.911, 95% CI = 5.141–15.447) and iodine deficiency (adjusted OR = 1.244, 95% CI = 1.031–1.502), while those with an SIC > 93.9 µg/L were at a higher risk of thyrotoxicosis (adjusted OR = 11.064, 95% CI = 6.324–19.357) and excessive iodine (adjusted OR = 11.064, 95% CI = 6.324–19.357). In contrast, the UIC was not correlated with thyroid diseases (p > 0.05). These findings indicate that the SIC is a potential biomarker for assessing individual iodine nutrition and thyroid dysfunction in pregnant women.