bluuebunny/crossref_metadata_2025 huggingface dataset:
Rutin Potentially Binds the Gamma Secretase Catalytic Site, Down Regulates the Notch Signaling Pathway and Reduces Sphere Formation in Colonospheres
Authors: Singh Atul Kumar , Shuaib Mohd , Prajapati Kumari Sunita , Kumar Shashank
Published: September 2022

Rutin, a natural flavonol, can modulate molecular signaling pathways and has considerable potential in cancer treatment. However, little is known about the effect of rutin on the notch signaling pathway (NSP) in cancer and cancer stem-like cells. In this study, we explored the effect of rutin on gamma secretase (GS, a putative notch signaling target) inhibition mediated NICD (Notch Intracellular Domain) production in colon cancer cells. Molecular docking, MM-GBSA, and Molecular dynamics (MD) simulation experiments were performed to check rutin’s GS catalytic site binding potential. The HCT-116 colon cancer and cancer stem-like cells (colonospheres) were utilized to validate the in silico findings. The NICD production, notch promoter assay, expression of notch target genes, and cancer stemness/self-renewal markers were studied at molecular levels. The results were compared with the Notch-1 siRNA transfected test cells. The in silico study revealed GS catalytic site binding potential in rutin. The in vitro results showed a decreased NICD formation, an altered notch target gene (E-cad, Hes-1, and Hey-1) expression, and a reduction in stemness/self-renewal markers (CD44, c-Myc, Nanog, and Sox2) in test cells in a time and dose-dependent manner. In conclusion, rutin inhibits the notch signaling pathway and reduces the stemness/self-renewal property in colon cancer cells and the colonospheres by targeting gamma secretase. The clinical efficacy of rutin in combination therapy in colon cancer may be studied in the future.
Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria
Authors: Norman Brendan P. , Davison Andrew S. , Hickton Bryony , Ross Gordon A. , Milan Anna M. , Hughes Andrew T. , Wilson Peter J. M. , Sutherland Hazel , Hughes Juliette H. , Roberts Norman B. , Bou-Gharios George , Gallagher James A. , Ranganath Lakshminarayan R.
Published: September 2022

Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was performed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. In total, we observed 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2–16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2–0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia.
Bayesian Measurement of Diagnostic Accuracy of the RT-PCR Test for COVID-19
Authors: Padhye Nikhil
Published: September 2022

Reverse transcription polymerase chain reaction (RT-PCR) targeting select genes of the SARS-CoV-2 RNA has been the main diagnostic tool in the global response to the COVID-19 pandemic. It took several months after the development of these molecular tests to assess their diagnostic performance in the population. The objective of this study is to demonstrate that it was possible to measure the diagnostic accuracy of the RT-PCR test at an early stage of the pandemic despite the absence of a gold standard. The study design is a secondary analysis of published data on 1014 patients in Wuhan, China, of whom 59.3% tested positive for COVID-19 in RT-PCR tests and 87.6% tested positive in chest computerized tomography (CT) exams. Previously ignored expert opinions in the form of verbal probability classifications of patients with conflicting test results have been utilized here to derive the informative prior distribution of the infected proportion. A Bayesian implementation of the Dawid-Skene model, typically used in the context of crowd-sourced data, was used to reconstruct the sensitivity and specificity of the diagnostic tests without the need for specifying a gold standard. The sensitivity of the RT-PCR diagnostic test developed by China CDC was estimated to be 0.707 (95% Cr I: 0.664, 0.753), while the specificity was 0.861 (95% Cr I: 0.781, 0.956). In contrast, chest CT was found to have high sensitivity (95% Cr I: 0.969, 1.000) but low specificity (95% Cr I: 0.477, 0.742). This estimate is similar to estimates that were found later in studies designed specifically for measuring the diagnostic performance of the RT-PCR test. The developed methods could be applied to assess diagnostic accuracy of new variants of SARS-CoV-2 in the future.
Magnetic Force-Assisted Nonlinear Three-Dimensional Wideband Energy Harvester Using Magnetostrictive/Piezoelectric Composite Transducers
Authors: Lin Zhiming , Li Hongyun , Lv Shaobo , Zhang Binbin , Wu Zhiyi , Yang Jin
Published: September 2022

This paper presents a nonlinear magnetoelectric energy harvester which has the potential to harvest vibrational energy over a wide bandwidth in arbitrary motion directions. Three springs with equal intersection angles are adopted to absorb the multi-directional vibration energy. Magnetic interaction between the magnets and ME transducers allows the nonlinear motion with enhanced harvesting frequency range. Very good agreement is observed between the numerical and experimental open-circuit voltage output frequency response curves. The experimental results show that the harvester can harvest vibrational energy in an arbitrary direction, exhibiting a further bandwidth of 5.2 Hz. This study provides a new solution to effectively use the magnetoelectric energy harvester for multi-directional and bandwidth vibrational energy scavenging in the surrounding environment.
Rapid Fabrication of Low-Cost Thermal Bubble-Driven Micro-Pumps
Authors: Hayes Brandon , Smith Lawrence , Kabutz Heiko , Hayes Austin C. , Whiting Gregory L. , Jayaram Kaushik , MacCurdy Robert
Published: September 2022

Thermal bubble-driven micro-pumps are an upcoming actuation technology that can be directly integrated into micro/mesofluidic channels to displace fluid without any moving parts. These pumps consist of high power micro-resistors, which we term thermal micro-pump (TMP) resistors, that locally boil fluid at the resistor surface in microseconds creating a vapor bubble to perform mechanical work. Conventional fabrication approaches of thermal bubble-driven micro-pumps and associated microfluidics have utilized semiconductor micro-fabrication techniques requiring expensive tooling with long turn around times on the order of weeks to months. In this study, we present a low-cost approach to rapidly fabricate and test thermal bubble-driven micro-pumps with associated microfluidics utilizing commercial substrates (indium tin oxide, ITO, and fluorine doped tin oxide, FTO, coated glass) and tooling (laser cutter). The presented fabrication approach greatly reduces the turn around time from weeks/months for conventional micro-fabrication to a matter of hours/days allowing acceleration of thermal bubble-driven micro-pump research and development (R&D) learning cycles.
Recent Progress of Terahertz Spatial Light Modulators: Materials, Principles and Applications
Authors: Guan Shengnan , Cheng Jierong , Chang Shengjiang
Published: September 2022

Terahertz (THz) technology offers unparalleled opportunities in a wide variety of applications, ranging from imaging and spectroscopy to communications and quality control, where lack of efficient modulation devices poses a major bottleneck. Spatial modulation allows for dynamically encoding various spatial information into the THz wavefront by electrical or optical control. It plays a key role in single-pixel imaging, beam scanning and wavefront shaping. Although mature techniques from the microwave and optical band are not readily applicable when scaled to the THz band, the rise of metasurfaces and the advance of new materials do inspire new possibilities. In this review, we summarize the recent progress of THz spatial light modulators from the perspective of functional materials and analyze their modulation principles, specifications, applications and possible challenges. We envision new advances of this technique in the near future to promote THz applications in different fields.
Dynamic Mechanics and Energy Dissipation of Saturated Layered Phyllite
Authors: Liu Guangjin , Peng Yaxiong , Zuo Qingjun , Su Ying , Wu Li
Published: September 2022

This paper is a study of the dynamic mechanics and energy dissipation of saturated layered phyllite. Using the Split-Hopkinson pressure bar system, the mechanical properties and energy dissipation law of the sample during dynamic loading in the test were analyzed. The results show that the weakening effect of water on the phyllite rock body will have a great impact on its mechanical properties, strain rate sensitivity damage mode, and fracture energy dissipation. The values of mechanical parameters such as the modulus of elasticity and compressive strength of the specimens in the test varied with the dip angle of the layer with 0° > 90° > 30° > 60°, and the mechanical parameters of the specimens in the saturated state were smaller than those of the dry specimens. The damage of the sample is mainly in the form of crushing damage at 0° dip angle, shear damage along the laminar surface at 30° and 60°, and destabilization damage of the compression bar at 90° dip angle, with higher fragmentation of the sample in the saturated state. The energy dissipation densities of different inclination samples in the saturated state of schist are greater than those in the dry state, with the highest energy dissipation density in the 0° inclination sample and the lowest in the 90° inclination sample. Both the mean strain rate and compressive strength of the samples showed a multiplicative power relationship with the crushing energy dissipation density of the samples, showing a strong strain rate correlation. These results indicate that the use of rock crushing energy dissipation density can better reflect the strength characteristics of phyllite samples under dynamic loading.
Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator
Authors: Hernández-Caballero Marta Elena , Sierra-Ramírez José Alfredo , Villalobos-Valencia Ricardo , Seseña-Méndez Emmanuel
Published: September 2022

Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy—such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation—through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/β-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment.
Using the Cyclotide Scaffold for Targeting Biomolecular Interactions in Drug Development
Authors: Jacob Binu , Vogelaar Alicia , Cadenas Enrique , Camarero Julio A.
Published: September 2022

This review provides an overview of the properties of cyclotides and their potential for developing novel peptide-based therapeutics. The selective disruption of protein–protein interactions remains challenging, as the interacting surfaces are relatively large and flat. However, highly constrained polypeptide-based molecular frameworks with cell-permeability properties, such as the cyclotide scaffold, have shown great promise for targeting those biomolecular interactions. The use of molecular techniques, such as epitope grafting and molecular evolution employing the cyclotide scaffold, has shown to be highly effective for selecting bioactive cyclotides.
Synthesis of Graphene-Based Nanocomposites for Environmental Remediation Applications: A Review
Authors: Goyat Rohit , Saharan Yajvinder , Singh Joginder , Umar Ahmad , Akbar Sheikh
Published: September 2022

The term graphene was coined using the prefix “graph” taken from graphite and the suffix “-ene” for the C=C bond, by Boehm et al. in 1986. The synthesis of graphene can be done using various methods. The synthesized graphene was further oxidized to graphene oxide (GO) using different methods, to enhance its multitude of applications. Graphene oxide (GO) is the oxidized analogy of graphene, familiar as the only intermediate or precursor for obtaining the latter at a large scale. Graphene oxide has recently obtained enormous popularity in the energy, environment, sensor, and biomedical fields and has been handsomely exploited for water purification membranes. GO is a unique class of mechanically robust, ultrathin, high flux, high-selectivity, and fouling-resistant separation membranes that provide opportunities to advance water desalination technologies. The facile synthesis of GO membranes opens the doors for ideal next-generation membranes as cost-effective and sustainable alternative to long existing thin-film composite membranes for water purification applications. Many types of GO–metal oxide nanocomposites have been used to eradicate the problem of metal ions, halomethanes, other organic pollutants, and different colors from water bodies, making water fit for further use. Furthermore, to enhance the applications of GO/metal oxide nanocomposites, they were deposited on polymeric membranes for water purification due to their relatively low-cost, clear pore-forming mechanism and higher flexibility compared to inorganic membranes. Along with other applications, using these nanocomposites in the preparation of membranes not only resulted in excellent fouling resistance but also could be a possible solution to overcome the trade-off between water permeability and solute selectivity. Hence, a GO/metal oxide nanocomposite could improve overall performance, including antibacterial properties, strength, roughness, pore size, and the surface hydrophilicity of the membrane. In this review, we highlight the structure and synthesis of graphene, as well as graphene oxide, and its decoration with a polymeric membrane for further applications.
Effect of Substrates Performance on the Microstructure and Properties of Phosphate Chemical Conversion Coatings on Metal Surfaces
Authors: Du Chunmiao , Zuo Kangqing , Ma Zongliang , Zhao Minru , Li Yibo , Tian Shuai , Lu Yupeng , Xiao Guiyong
Published: September 2022

Phosphate chemical conversion (PCC) technology has attracted extensive attention for its ability to regulate the surface properties of biomedical metals. However, titanium (Ti)-based alloys exhibit inertia because of the native passive layer, whereas zinc (Zn)-based alloys show high activity in acidic PCC solutions. The substrate performance affects the chemical reaction in the phosphating solution, which further leads to diversity in coating properties. In this work, the zinc-phosphate (ZnP) coatings are prepared on Ti alloy (TA) and Zn alloy (ZA) substrates using the PCC method, respectively. The coatings prepared herein are detected by a scanning electron microscope (SEM), X-ray diffractometer (XRD), laser scanning confocal microscope (LSCM), universal testing machine, contact angle goniometer, and electrochemical workstation system. The results show that the substrate performance has little effect on the phase composition but can significantly affect the crystal microstructure, thickness, and bonding strength of the coatings. In addition, the ZnP coatings improve the surface roughness of the substrates and show good hydrophilicity and electrochemical corrosion resistance. The formation mechanism of the ZnP coating is revealed using potential-time curves, indicating that the metal–solution interfacial reaction plays a dominant role in the deposition process.
Electrolyte Analysis in Blood Serum by Laser-Induced Breakdown Spectroscopy Using a Portable Laser
Authors: Feng Zhongqi , Li Shuaishuai , Gu Tianyu , Zhou Xiaofei , Zhang Zixu , Yang Zhifu , Hou Jiajia , Zhu Jiangfeng , Zhang Dacheng
Published: September 2022

The fast and reliable analysis of electrolytes such as K, Na, Ca in human blood serum has become an indispensable tool for diagnosing and preventing diseases. Laser-induced breakdown spectroscopy (LIBS) has been demonstrated as a powerful analytical technique on elements. To apply LIBS to the quantitative analysis of electrolyte elements in real time, a self-developed portable laser was used to measure blood serum samples supported by glass slides and filter paper in this work. The partial least squares regression (PLSR) method was employed for predicting the concentrations of K, Na, Ca from serum LIBS spectra. Great prediction accuracies with excellent linearity were obtained for the serum samples, both on glass slides and filter paper. For blood serum on glass slides, the prediction accuracies for K, Na, Ca were 1.45%, 0.61% and 3.80%. Moreover, for blood serum on filter paper, the corresponding prediction accuracies were 7.47%, 1.56% and 0.52%. The results show that LIBS using a portable laser with the assistance of PLSR can be used for accurate quantitative analysis of elements in blood serum in real time. This work reveals that the handheld LIBS instruments will be an excellent tool for real-time clinical practice.
Recent Progress in Identifying Bacteria with Fluorescent Probes
Authors: Ji Yuefeng , Li Guanhao , Wang Juan , Piao Chunxiang , Zhou Xin
Published: September 2022

The development of new techniques to rapidly and accurately detect bacteria has drawn continuous attention due to the potential threats posed by bacteria to human health and safety. Recently, a novel strategy based on fluorescent probes has drawn considerable interest for the detection of bacteria due to its high selectivity, fast response, and simple operation. In this review, we summarize the recent progress on fluorescent probes for the specific recognition and discrimination of Gram-negative and Gram-positive bacteria. In particular, we outline current design strategies, such as targeting of the differences in surface components, cell wall components, endogenous enzymes, surface charge, and hydrophobicity of various kinds of bacteria to develop various fluorescent sensors (organic small-molecule fluorescent probes, nanoprobes, and metal ion probes). We also emphasize the application of organic molecules in probe recognition elements. We hope that this review can stimulate this research area in bacterial detection and imaging in the future.
A Box–Behnken Extraction Design and Hepatoprotective Effect of Isolated Eupalitin-3-O-β-D-Galactopyranoside from Boerhavia diffusa Linn.
Authors: Thajudeen Kamal Y. , Asiri Yahya I. , Salam Shahana , Thorakkattil Shabeer Ali , Rahamathulla Mohamed , Uoorakkottil Ilyas
Published: September 2022

The objectives of this study were to optimize and quantify the maximum percentage yield of eupalitin-3-O-β-D-galactopyranosidefrom Boerhavia diffusa leaves using response surface methodology (RSM), as well as to demonstrate the hepatoprotective benefits of the bioactive compound. The Box–Behnken experimental design was utilized to optimize the eupalitin-3-O-β-D-galactopyranoside extraction procedure, which also looked at the extraction duration, temperature, and solvent concentration as independent variables. Boerhaviadiffusa leaves were extracted, and n-hexane, chloroform, ethyl acetate, and water were used to fractionate the dried extracts. The dried ethyl acetate fraction was thoroughly mixed in hot methanol and stored overnight in the refrigerator. The cold methanol was filtered, the solid was separated, and hot methanol was used many times to re-crystallize the solid to obtain pure eupalitin-3-O-β-D-galactopyranoside (0.1578% w/w). The proposed HPTLC method for the validation and quantification of eupalitin-3-O-β-D-galactopyranosidewassuccessfully validated and developed. The linearity (R2 = 0.994), detection limit (30 ng), and quantification limit (100 ng) of the method, as well as its range (100–5000 ng), inter and intraday precision (0.67% and 0.991% RSD), specificity, and accuracy (99.78% RSD), were all validated as satisfactory. The separation of the eupalitin-3-O-β-D-galactopyranoside band was achieved on an HPTLC plate using toluene:acetone:water (5:15:1 v/v) as a developing system. The Box–Behnken statistical design was used to determine the best optimization method, which was found to be extraction time (90 min), temperature (45 °C), and solvent ratio (80% methanol in water v/v) for eupalitin-3-O-β-D-galactopyranoside. Standard silymarin ranged from 80.2% at 100 µg/mL to 86.94% at 500 µg/mL in terms of significant high hepatoprotection (cell induced with carbon tetrachloride 0.1%), whereas isolated eupalitin-3-O-β-D-galactopyranoside ranged from 62.62% at 500 µg/mL to 70.23% at 1000 µg/mL. More recently, it is a source of structurally unique flavonoid compounds that may offer opportunities for developing novel semi-synthetic molecules.
Effect of the Addition of Corn Husk Cellulose Nanocrystals in the Development of a Novel Edible Film
Authors: Choque-Quispe David , Choque-Quispe Yudith , Ligarda-Samanez Carlos A. , Peralta-Guevara Diego E. , Solano-Reynoso Aydeé M. , Ramos-Pacheco Betsy S. , Taipe-Pardo Fredy , Martínez-Huamán Edgar L. , Aguirre Landa John Peter , Agreda Cerna Henrry W. , Loayza-Céspedes Julio C. , Zamalloa-Puma Miluska M. , Álvarez-López Genaro Julio , Zamalloa-Puma Alan , Moscoso-Moscoso Elibet , Quispe-Quispe Yadyra
Published: September 2022

The cellulose from agroindustrial waste can be treated and converted into nanocrystals or nanofibers. It could be used to produce biodegradable and edible films, contributing to the circular economy and being environmentally friendly. This research aimed to develop an edible film elaborated with activated cellulose nanocrystals, native potato starch, and glycerin. The activated cellulose nanocrystals were obtained by basic/acid digestion and esterification with citric acid from corn husks. The starch was extracted from the native potato cultivated at 3500 m of altitude. Four film formulations were elaborated with potato starch (2.6 to 4.4%), cellulose nanocrystals (0.0 to 0.12%), and glycerin (3.0 to 4.2%), by thermoforming at 60 °C. It was observed that the cellulose nanocrystals reported an average size of 676.0 nm. The films mainly present hydroxyl, carbonyl, and carboxyl groups that stabilize the polymeric matrix. It was observed that the addition of cellulose nanocrystals in the films significantly increased (p-value < 0.05) water activity (0.409 to 0.447), whiteness index (96.92 to 97.27), and organic carbon content. In opposition to gelatinization temperature (156.7 to 150.1 °C), transparency (6.69 to 6.17), resistance to traction (22.29 to 14.33 N/mm), and solubility in acidic, basic, ethanol, and water media decreased. However, no significant differences were observed in the thermal decomposition of the films evaluated through TGA analysis. The addition of cellulose nanocrystals in the films gives it good mechanical and thermal resistance qualities, with low solubility, making it a potential food-coating material.
Effects of Cardiac Rehabilitation and Diet Counselling on Adherence to the Mediterranean Lifestyle in Patients after Myocardial Infarction
Authors: Novaković Marko , Rajkovič Uroš , Košuta Daniel , Tršan Jure , Fras Zlatko , Jug Borut
Published: September 2022

Adherence to the Mediterranean lifestyle—as captured by the Medlife Index Questionnaire (i.e., encompassing a Mediterranean diet as well as other aspects of healthy living, such as food preparation, physical activity, and socializing)—has been associated with reduced cardiovascular events in healthy individuals. In the present study, we sought to determine the adherence to, and the effect of comprehensive cardiac rehabilitation on, Mediterranean lifestyle adherence in patients after myocardial infarction. We included 121 patients (mean age, 55 years; women, 37%) undergoing comprehensive cardiac rehabilitation—i.e., exercise training 3 times per week for 12 weeks plus dedicated workshops promoting the Mediterranean lifestyle. Before and after cardiac rehabilitation, patients completed the Medlife Index Questionnaire. High baseline adherence was associated with favourable glucose (5.39 vs. 6.1 mmol/L; p < 0.001), triglycerides (1.1 vs. 1.5 mmol/L; p = 0.002), and HDL cholesterol levels (1.32 vs. 1.12 mmol/L; p = 0.032). More importantly, the Medlife Score significantly improved following comprehensive cardiac rehabilitation in patients with low baseline adherence (from 13.8 to 16.7 points; p < 0.001), but not in patients with high baseline adherence (from 19.4 to 18.8 points; p = 0.205). Our findings suggested that Mediterranean lifestyle promotion during cardiac rehabilitation improved adherence to the Mediterranean lifestyle, especially in low-adherence patients.
Bifidobacterium longum 070103 Fermented Milk Improve Glucose and Lipid Metabolism Disorders by Regulating Gut Microbiota in Mice
Authors: Jiang Tong , Li Ying , Li Longyan , Liang Tingting , Du Mingzhu , Yang Lingshuang , Yang Juan , Yang Runshi , Zhao Hui , Chen Moutong , Ding Yu , Zhang Jumei , Wang Juan , Xie Xinqiang , Wu Qingping
Published: September 2022

Background: Fermented milk is beneficial for metabolic disorders, while the underlying mechanisms of action remain unclear. This study explored the benefits and underlying mechanisms of Bifidobacterium longum 070103 fermented milk (BLFM) in thirteen-week high-fat and high-sugar (HFHS) fed mice using omics techniques. Methods and results: BLFM with activated glucokinase (GK) was screened by a double-enzyme coupling method. After supplementing BLFM with 10 mL/kg BW per day, fasting blood glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and leptin were significantly reduced compared with the HFHS group. Among them, the final body weight (BW), epididymal fat, perirenal fat, and brown fat in BLFM group had better change trends than Lacticaseibacillus rhamnosus GG fermented milk (LGGFM) group. The amplicon and metabolomic data analysis identified Bifibacterium as a key gut microbiota at regulating glycolipid metabolism. BLFM reverses HFHS-induced reduction in bifidobacteria abundance. Further studies showed that BLFM significantly reduces the content of 3-indoxyl sulofphate associated with intestinal barrier damage. In addition, mice treated with BLFM improved BW, glucose tolerance, insulin resistance, and hepatic steatosis. Conclusion: BLFM consumption attenuates obesity and related symptoms in HFHS-fed mice probably via the modulation of gut microbes and metabolites.
Estimation of Left Ventricular Ejection Fraction Using Cardiovascular Hemodynamic Parameters and Pulse Morphological Characteristics with Machine Learning Algorithms
Authors: Liu Shing-Hong , Yang Zhi-Kai , Pan Kuo-Li , Zhu Xin , Chen Wenxi
Published: September 2022

It is estimated that 360,000 patients have suffered from heart failure (HF) in Taiwan, mostly those over the age of 65 years, who need long-term medication and daily healthcare to reduce the risk of mortality. The left ventricular ejection fraction (LVEF) is an important index to diagnose the HF. The goal of this study is to estimate the LVEF using the cardiovascular hemodynamic parameters, morphological characteristics of pulse, and bodily information with two machine learning algorithms. Twenty patients with HF who have been treated for at least six to nine months participated in this study. The self-constructing neural fuzzy inference network (SoNFIN) and XGBoost regression models were used to estimate their LVEF. A total of 193 training samples and 118 test samples were obtained. The recursive feature elimination algorithm is used to choose the optimal parameter set. The results show that the estimating root-mean-square errors (ERMS) of SoNFIN and XGBoost are 6.9 ± 2.3% and 6.4 ± 2.4%, by comparing with echocardiography as the ground truth, respectively. The benefit of this study is that the LVEF could be measured by the non-medical image method conveniently. Thus, the proposed method may arrive at an application level for clinical practice in the future.
Characterization of Choline Nutriture among Adults and Children with Phenylketonuria
Authors: Schoen Meriah S. , Ramakrishnan Usha , Alvarez Jessica A. , Ziegler Thomas R. , Cui Xiangqin , Singh Rani H.
Published: September 2022

Choline is an essential nutrient for brain development and function that is attained through high-protein foods, which are limited in the phenylalanine-restricted diet of people with phenylketonuria (PKU). This study compared choline consumption among individuals with PKU to a reference sample from the National Health and Nutrition Examination Survey (NHANES), and identified treatment and diet-related factors that may modulate choline needs. Participants were individuals with PKU (n = 120, 4–61 years) managed with dietary therapy alone (n = 49), sapropterin dihydrochloride for ≥1 year (n = 38), or pegvaliase for ≥1 year with no medical food (n = 33). NHANES participants were not pregnant or nursing and came from the 2015–2018 cycles (n = 10,681, 4–70 years). Dietary intake data were used to estimate total usual intake distributions for choline, and mean probability of adequacy (MPA) was calculated as a summary index of nutrient adequacy for four methyl-donor/co-factor nutrients that impact choline utilization (folate, vitamin B12, vitamin B6, and methionine). Only 10.8% (SE: 2.98) of the total PKU sample (14.7% [SE: 4.03] of children; 6.8% [SE: 2.89] of adults) achieved the adequate intake (AI) for choline, while 12.2% (SE:0.79) of the NHANES sample met the recommended level. Adults receiving pegvaliase were the most likely to exceed the AI for choline (14.82% [SE: 4.48]), while adults who were on diet therapy alone were the least likely (5.59% [SE: 2.95]). Without fortified medical foods, individuals on diet therapy and sapropterin would not be able to achieve the AI, and MPA for other methyl donor/co-factor nutrients would be reduced. More frequent monitoring of choline intake and increased choline fortification of medical foods could benefit this population.
Greater Adherence to Cardioprotective Diet Can Reduce Inflammatory Bowel Disease Risk: A Longitudinal Cohort Study
Authors: Fu Tian , Ye Shuyu , Sun Yuhao , Dan Lintao , Wang Xiaoyan , Chen Jie
Published: September 2022

Background: The cardioprotective diet was reported to be associated with several chronic cardiometabolic diseases through an anti-inflammation effect. However, the association between the cardioprotective diet and the risk of inflammatory bowel disease (IBD) was unclear and deserved to be further explored. Methods: We calculated the cardioprotective diet score based on the consumptions of seven common food groups using the validated food frequency questionnaire data in the UK Biobank. Incident IBD was ascertained from primary care data, inpatient data, and the death registry. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the cardioprotective diet score and the risk of IBD. Results: During a mean follow-up of 12.1 years, we documented 2717 incident IBD cases, including 851 cases of Crohn’s disease and 1866 cases of ulcerative colitis. Compared to participants with a cardioprotective diet score of 0–1, we observed a decreased risk of IBD among participants with cardioprotective diet scores of 3 (HR 0.85, 95% CI 0.73–0.99), 4 (HR 0.84, 95% CI 0.72–0.98), and 5–7 (HR 0.77, 95% CI 0.66–0.89) (p-trend < 0.001). Conclusions: A greater adherence to the cardioprotective diet was associated with a lower risk of IBD. Our finding highlighted the importance of focusing on the cardioprotective diet to prevent IBD.
Development and Validation of a Novel Waist Girth-Based Equation to Estimate Fat Mass in Young Colombian Elite Athletes (F20CA Equation): A STROSA-Based Study
Authors: Bonilla Diego A. , Duque-Zuluaga Leidy T. , Muñoz-Urrego Laura P. , Franco-Hoyos Katherine , Agudelo-Martínez Alejandra , Kammerer-López Maximiliano , Petro Jorge L. , Kreider Richard B.
Published: September 2022

The estimation of body fat percentage (%BF) from anthropometry-related data requires population-specific equations to avoid incorrect interpretations in young athletes. Waist girth (WG) has been described as potential predictor of fat mass (FM) in several populations; however, there are no valid WG-based equations to estimate body composition in young Colombian athletes. The aim of this STandardisierte BerichtsROutine für Sekundärdaten Analysen STROSA-based study was twofold: i) to validate the relative fat mass (RFM) and its pediatric version (RFMp) compared to dual-energy x-ray absorptiometry (DXA) and ii) to develop a new equation (F20CA) to estimate the fat mass in Colombian children and adolescent elite athletes. A total of 114 young athletes that belong to the ‘Team Medellín’ program (58F, 56M; 51 children, 63 adolescents; 14.85 [2.38] years; 55.09 [12.16] kg; 162.38 [11.53] cm) participated in this cross-sectional study. The statistical analysis revealed a poor correlation, agreement and concordance of RFMp and RFM estimations with DXA measurements. After model specification using both Ordinary Least Square method and Bayesian analysis, the regression output revealed that sex, body mass-to-waist ratio, and waist-to-stature ratio were the statistically significant predictor variables that account for variability in FM. The new F20CA equation is expressed as FM (kg) = 5.46 ∗ (Sex) + 0.21 ∗ (BM/W [kg/m]) + 81.7 ∗ (W/Stature [cm/cm]) − 41.8 (R2 = 0.683; SEE = 2.468 kg), where sex is 0 for males and 1 for females. A moderate-to-high correlation and agreement of the F20CA was confirmed within the internal validation data set (R2 = 0.689; ICC [95%CI] = 0.805 [0.615, 0.904]; RMSE = 2.613 kg). The Bland–Altman analysis corroborated the high concordance between the reference method (DXA) and the F20CA-estimated FM (bias [95% LoA] = 1.02 [−3.77, 5.81] kg), indicating the two methods could be considered interchangeable. Even though external validation is needed, practitioners are advised to use the F20CA in young Colombian athletes with similar characteristics to those who participated in this study.
Usnic Acid-Loaded Polymeric Micelles: An Optimal Migrastatic-Acting Formulation in Human SH-SY5Y Neuroblastoma Cells
Authors: Vasarri Marzia , Ponti Linda , Degl’Innocenti Donatella , Bergonzi Maria Camilla
Published: September 2022

Usnic acid (UA) is one of the most abundant and common metabolites of lichens, known for its numerous pharmacological properties. Nevertheless, it presents some criticalities that severely limit its use in therapy: poor solubility in water and significant hepatotoxicity. Soluplus and Solutol HS15 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) were employed to develop polymeric micelles (UA–PM). The chemical and physical properties of the system were characterized, including the size, homogeneity, zeta potential, critical micellar concentration (CMC), encapsulation efficiency (EE%), and in vitro release. The freeze-drying process was considered to prevent agglomeration and improve the stability of the formulation. The stability of the micelles and the freeze-dried product (UA–PML) was also evaluated. The anti-migratory activity of UA and UA–PM was evaluated in human neuroblastoma SH-SY5Y cells using the wound healing assay. Their effect on the activity of metalloproteinases (MMP)-2/9 involved in the migration process of cells was verified by gelatin zymography. The optimized UA–PM contained Soluplus, Solutol HS15, and TPGS in a 1:4:0.5 weight ratio and increased the aqueous solubility to about 150-fold solubilized, solubilizing 0.5 mg/mL of UA. UA–PM has a small size (45.39 ± 0.31 nm), a polydispersity index (PDI) of 0.26 ± 0.01, and an EE% of 82.13 ± 5.57%. The colloidal dispersion was stable only for 9 days at 4 °C, while the freeze-drying process improved the stability for up to 30 days. UA was released for a prolonged period during the in vitro release study. The in vitro cell-based experiments showed that UA–PM (0.2 µg/mL) inhibited SH-SY5Y cell migration and the gelatinolytic activity of MMP-2/9 in culture media, while free UA at the same concentration exerted no biological activity. This study demonstrates that polymeric micelles are an excellent formulation for UA to manifest inhibitory action on neuroblastoma cell migration.
The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect
Authors: Barbalata Cristina-Ioana , Porfire Alina Silvia , Casian Tibor , Muntean Dana , Rus Iulia , Tertis Mihaela , Cristea Cecilia , Pop Anca , Cherfan Julien , Loghin Felicia , Tomuta Ioan
Published: September 2022

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.e., phospholipid, SIM and DOX concentration, which were assessed in an optimization experimental design with the purpose of designing an optimal formulation. The optimal formulation, meeting the established quality profile, was additionally characterized in terms of the release profile and antiproliferative effects. During dissolution studies, a novel chronoamperometric method was used for the simultaneous quantification of SIM and DOX. The obtained data confirmed the similarity of this method with a validated HPLC method. The anticancer potential of the optimal formulation was tested against two human cancerous cell lines, namely T47D-KBluc human mammary ductal carcinoma cell line and A549 human pulmonary cancer cell line. The results highlighted that the antiproliferative effect of the optimal formulation is concentration dependent and favors a synergistic effect of the two drugs.
Findings on In Vitro Transporter-Mediated Drug Interactions and Their Follow-Up Actions for Labeling: Analysis of Drugs Approved by US FDA between 2017 and 2021
Authors: Lee Kyeong-Ryoon , Chang Ji-Eun , Yoon Jongmin , Jin Hyojeong , Chae Yoon-Jee
Published: September 2022

Understanding possible follow-up actions on in vitro findings helps determine the necessity of labeling for drug interactions. We analyzed information for in vitro findings on transporter-mediated interactions of drugs approved by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research for the last five years (i.e., 2017–2021) and their follow-up actions for labeling. Higher R values than the pre-defined cut-off were observed with 3.7–39.1% inhibitor drugs in a simple prediction. Among these drugs, 16–41.7% were labeled with their potential drug interactions, while results of supporting studies or scientific rationales were submitted for the other drugs leading to no interaction labeling. In vitro transporter substrates were reported with 1.7–67.6% of drugs. The interaction labels for these substrate drugs were observed in up to 40% of drugs, while the other drugs were not labeled on the drug interactions with claims for their low interaction potential, evidenced by clinical studies or scientific rationales. The systematic and comprehensive analysis in this study will provide insight into the management of in vitro findings for transporter substrate or inhibitor drugs.
Mesoporous Silica Particles Functionalized with Newly Extracted Fish Oil (Omeg@Silica) Reducing IL-8 Counteract Cell Migration in NSCLC Cell Lines
Authors: D’Anna Claudia , Di Sano Caterina , Di Vincenzo Serena , Taverna Simona , Cammarata Giuseppe , Scurria Antonino , Pagliaro Mario , Ciriminna Rosaria , Pace Elisabetta
Published: September 2022

Lung cancer is one of the leading forms of cancer in developed countries. Interleukin-8 (IL-8), a pro-inflammatory cytokine, exerts relevant effects in cancer growth and progression, including angiogenesis and metastasis in lung cancer. Mesoporous silica particles, functionalized with newly extracted fish oil (Omeg@Silica), are more effective than the fish oil alone in anti-proliferative and pro-apoptotic effects in non-small cell lung cancer (NSCLC) cell lines. The mechanisms that explain this efficacy are not yet understood. The aim of the present study is therefore to decipher the anti-cancer effects of a formulation of Omeg@Silica in aqueous ethanol (FOS) in adenocarcinoma (A549) and muco-epidermoid (NCI-H292) lung cancer cells, evaluating cell migration, as well as IL-8, NF-κB, and miRNA-21 expression. Results show that in both cell lines, FOS was more efficient than oil alone, in decreasing cell migration and IL-8 gene expression. FOS reduced IL-8 protein release in both cell lines, but this effect was only stronger than the oil alone in A549. In A549, FOS was able to reduce miRNA-21 and transcription factor NF-κB nuclear expression. Taken together, these data support the potential use of the Omeg@Silica as an add-on therapy for NSCLC. Dedicated studies which prove clinical efficacy are needed.
Cancer Treatment and Immunotherapy during Pregnancy
Authors: Koutras Antonios , Ntounis Thomas , Fasoulakis Zacharias , Papalios Theodoros , Pittokopitou Savia , Prokopakis Ioannis , Syllaios Athanasios , Valsamaki Asimina , Chionis Athanasios , Symeonidis Panagiotis , Samara Athina A. , Pagkalos Athanasios , Pergialiotis Vasilios , Theodora Marianna , Antsaklis Panos , Daskalakis Georgios , Kontomanolis Emmanuel N.
Published: September 2022

Background/aim: Immunotherapy has, in recent years, witnessed an expansion in its indications for the treatment of cancer. Coupled with the fact that, nowadays, even more women choose to postpone parenthood, thus increasing their chances of having some kind of malignancy during pregnancy, more and more women are eligible for receiving immunotherapy during this period of their lives. The cases of cancer diagnosed during pregnancy is an ever-increasing trend nowadays. Materials and methods: The oncologists and clinicians treating women often face a range of ethical and therapeutic dilemmas due to the particularity of the patient’s conditions. The primary concern is the protection of the mother, firstly, and then the fetus (through adjustments to the various treatment regimens) if possible. Results and conclusions: Oncological drugs, radiation therapy, surgery, or a combination of all the above methods are selected, depending on the case. In this project, we studied the oncology drugs used for various types of gestational cancer, their appropriateness and timing, as well as their possible effects on the parent and embryo upon their administration. Various studies have shown that the administration of oncological drugs should be postponed until at least after the first trimester of pregnancy.
Genotyping of UGT1A1*80 as an Alternative to UGT1A1*28 Genotyping in Spain
Authors: Bravo-Gómez Adrián , Salvador-Martín Sara , Zapata-Cobo Paula , Sanjurjo-Sáez María , López-Fernández Luis Andrés
Published: September 2022

Background: The variant rs34983651 (UGT1A1*28) and its genotyping are used to prevent irinotecan-induced toxicity. Several variants are in close linkage disequilibrium. Our objective was to evaluate the potential correlation of genotyping UGT1A1*80 instead of UGT1A1*28 in different populations. Methods: We studied SNPs in linkage disequilibrium with UGT1A1*28 in several populations and selected rs887829 to develop an inexpensive and rapid genotyping method and compare it with the one we currently use for UGT1A1*28 genotyping. Samples from cancer patients (n = 701) already tested using PCR and electrophoresis prior to treatment with irinotecan for rs34983651 (UGT1A1*28) in a Spanish hospital were genotyped for rs887829 (UGT1A1*80) using real-time PCR with a TaqMan probe. Results: We observed a complete match for both genotypes, except in one sample. This method was 100% efficient in correctly genotyping *28/*28 patients, 99.68% efficient for *1/*28, and 100% efficient for *1/*1. Linkage disequilibrium between populations showed the Iberian population to be the most suitable for the clinical use of UGT1A1*80. This method is less expensive and the time to decision is shorter. Conclusion: Genotyping of rs887829 using the proposed method may be used to substitute genotyping of rs34983651 as a pharmacogenetics test in cancer patients prior to starting irinotecan-based treatments, mainly in the Iberian population. In addition, it is less expensive than other conventional methods and easy to implement, with a shorter time to decision than UGT1A1*28.