bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin Derivative C66 Suppresses Pancreatic Cancer Progression through the Inhibition of JNK-Mediated Inflammation
Authors: Chen Hongjin , Jiang Yuchen , Liu Rongdiao , Deng Jie , Chen Qinbo , Chen Lingfeng , Liang Guang , Chen Xiong , Xu Zheng
Published: May 2022

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1β, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.
Amphotericin B and Curcumin Co-Loaded Porous Microparticles as a Sustained Release System against Candida albicans
Authors: Xue Baiji , Yu Yanhua , Peng Guoqiang , Sun Mengmeng , Lv Peng , Li Xuefeng
Published: May 2022

Amphotericin B (AMB) is an antifungal drug used for serious fungal infections. However, AMB has adverse reactions such as nephrotoxicity, which limit the clinical application of AMB alone or in combination with other antifungal drugs. Nano or micro drug delivery systems (DDS) have been proven to be effective in reducing the toxic and side effects of drugs. Further, the combination of AMB with other compounds with antifungal activity, such as curcumin (CM), may enhance the synergistic effects. Herein, AMB and CM were co-loaded into porous poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) to prepare AMB/CM-PLGA MPs. The AMB/CM-PLGA MPs showed a remarkably reduced hemolysis (62.2 ± 0.6%) compared to AMB (80.9 ± 1.1%). The nephrotoxicity of AMB/CM-PLGA MPs is significantly lower than that of AMB. In vitro, AMB/CM-PLGA MPs had better inhibitory effects on the adhesion and biofilm formation of Candida albicans compared with AMB. Experiments on mice infected with C. albicans showed that AMB/CM-PLGA MPs have a better therapeutic effect than AMB in vivo. In summary, AMB/CM-PLGA MPs may be a novel and promising therapeutic candidate for fungal infection.
The First Silver-Based Plasmonic Nanomaterial for Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy with Magnetic Properties
Authors: Michałowska Aleksandra , Kudelski Andrzej
Published: May 2022

Nanostructures made of magnetic cores (from Fe3O4) with attached silver plasmonic nanostructures were covered with a very thin layer of silica. The (Fe3O4@Ag)@SiO2 magnetic–plasmonic nanomaterial can be manipulated using a magnetic field. For example, one can easily form homogeneous layers from this nanomaterial using a very simple procedure: deposition of a layer of a sol of such a nanostructure and evaporation of the solvent after placing the sample in a strong magnetic field. Due to the rapid magnetic immobilization of the magnetic–plasmonic nanomaterial on the investigated surface, no coffee-ring effect occurs during the evaporation of the solvent. In this contribution, we report the first example of a magnetic, silver-based plasmonic nanomaterial for shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). Nanoresonators based on silver plasmonic nanostructures locally enhance the intensity of the exciting electromagnetic radiation in a significantly broader frequency range than the previously used magnetic SHINERS nanoresonators with gold plasmonic nanostructures. Example applications where the resulting nanomaterial was used for the SHINERS investigation of a monolayer of mercaptobenzoic acid chemisorbed on platinum, and for a standard SERS determination of dopamine, are also presented.
Distinct Role of Mono-2-ethylhexyl Phthalate in Neuronal Transmission in Rat CA3 Hippocampal Neurons: Involvement of Ion Channels
Authors: Lu Yi , Wang Hong , Yang Junqing , Jiang Wengao , Xin Hong , Luo Ying , Loya-López Santiago , Gu Huaiyu , Ran Dongzhi
Published: May 2022

Mono-(2-ethylhexyl) phthalate (MEHP) is one of the main active metabolites of di-(2-ethylhexyl) phthalate (DEHP). In our previous works, by using rat and Drosophila models, we showed a disruption of neural function due to DEHP. However, the exact neural effects of MEHP are still unclear. To explore the effects of MEHP on the central nervous system, the electrophysiological properties of spontaneous action potential (sAP), mini-excitatory postsynaptic currents (mEPSCs), ion channels, including Na+, Ca2+, and K+ channels from rat CA3 hippocampal neurons area were assessed. Our data showed that MEHP (at the concentrations of 100 or 300 μM) decreased the amplitude of sAP and the frequency of mEPSCs. Additionally, MEHP (100 or 300 μM) significantly reduced the peak current density of Ca2+ channels, whereas only the concentration of 300 μM decreased the peak current density of Na+ and K+ channels. Therefore, our results indicate that exposure to MEHP could affect the neuronal excitability and synaptic plasticity of rat CA3 hippocampal neurons by inhibiting ion channels’ activity, implying the distinct role of MEHP in neural transmission.
Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Apremilast: In Vitro Evaluation and Pharmacokinetics Studies
Authors: Abushal Ahad S. , Aleanizy Fadilah S. , Alqahtani Fulwah Y. , Shakeel Faiyaz , Iqbal Muzaffar , Haq Nazrul , Alsarra Ibrahim A.
Published: May 2022

Psoriatic arthritis is an autoimmune disease of the joints that can lead to persistent inflammation, irreversible joint damage and disability. The current treatments are of limited efficacy and inconvenient. Apremilast (APR) immediate release tablets Otezla® have 20–33% bioavailability compared to the APR absolute bioavailability of 73%. As a result, self-nanoemulsifying drug delivery systems (SNEDDS) of APR were formulated to enhance APR’s solubility, dissolution, and oral bioavailability. The drug assay was carried out using a developed and validated HPLC method. Various thermodynamic tests were carried out on APR-SNEDDS. Stable SNEDDS were characterized then subjected to in vitro drug release studies via dialysis membrane. The optimum formulation was F9, which showed the maximum in vitro drug release (94.9%) over 24 h, and this was further investigated in in vivo studies. F9 was composed of 15% oil, 60% Smix, and 25% water and had the lowest droplet size (17.505 ± 0.247 nm), low PDI (0.147 ± 0.014), low ZP (−13.35 mV), highest %T (99.15 ± 0.131) and optimum increases in the relative bioavailability (703.66%) compared to APR suspension (100%) over 24 h. These findings showed that APR-SNEDDS is a possible alternative delivery system for APR. Further studies are warranted to evaluate the major factors that influence the encapsulation efficiency and stability of APR-containing SNEDDS.
Heterologous Biosynthesis of Health-Promoting Baicalein in Lycopersicon esculentum
Authors: Liao Jingjing , Xie Lei , Liu Tingyao , Mo Changming , Cui Shengrong , Jia Xunli , Huang Xiyang , Luo Zuliang , Ma Xiaojun
Published: May 2022

Baicalein is a valuable flavonoid isolated from the medicinal plant Scutellaria baicalensis Georgi, which exhibits intensive biological activities, such as anticancer and antiviral activities. However, its production is limited in the root with low yield. In this study, In-Fusion and 2A peptide linker were developed to assemble SbCLL-7, SbCHI, SbCHS-2, SbFNSII-2 and SbCYP82D1.1 genes driven by the AtPD7, CaMV 35S and AtUBQ10 promoters with HSP, E9 and NOS terminators, and were used to engineer baicalein biosynthesis in transgenic tomato plants. The genetically modified tomato plants with this construct synthesized baicalein, ranging from 150 ng/g to 558 ng/g FW (fresh weight). Baicalein-fortified tomatoes have the potential to be health-promoting fresh vegetables and provide an alternative source of baicalein production, with great prospects for market application.
Low-Cost Potentiometric Sensor for Chloride Measurement in Continuous Industrial Process Control
Authors: Vizza Martina , Marcantelli Patrick , Giovani Claudia , Giurlani Walter , Giusti Paolo , Fontanesi Claudio , Innocenti Massimo
Published: May 2022

Recently, the new updates in legislation about drinking water control and human health have increased the demand for novel electrochemical low-cost sensors, such as potentiometric ones. Nowadays, the determination of chloride ion in aqueous solutions has attracted great attention in several fields, from industrial processes to drinking water control. Indeed, chloride plays a crucial role in corrosion, also influencing the final taste of beverages, especially coffee. The main goal is to obtain devices suitable for continuous and real-time analysis. For these reasons, we investigated the possibility to develop an easy, low-cost potentiometric chloride sensor, able to perform analysis in aqueous mediums for long immersion time and reducing the need of periodic calibration. We realized a chloride ion selective electrode made of Ag/AgCl sintered pellet and we tested its response in model solutions compatible with drinking water. The sensor was able to produce a stable, reproducible, and accurate quantification of chloride in 900 s, without the need for a preliminary calibration test. This opens the route to potential applications of this sensor in continuous, in situ, and real time measurement of chloride ions in industrial processes, with a reduced need for periodic maintenance.
Predictive Multi Experiment Approach for the Determination of Conjugated Phenolic Compounds in Vegetal Matrices by Means of LC-MS/MS
Authors: Oliva Eleonora , Fanti Federico , Palmieri Sara , Viteritti Eduardo , Eugelio Fabiola , Pepe Alessia , Compagnone Dario , Sergi Manuel
Published: May 2022

Polyphenols (PCs) are a numerous class of bioactive molecules and are known for their antioxidant activity. In this work, the potential of the quadrupole/linear ion trap hybrid mass spectrometer (LIT-QqQ) was exploited to develop a semi-untargeted method for the identification of polyphenols in different food matrices: green coffee, Crocus sativus L. (saffron) and Humulus lupulus L. (hop). Several conjugate forms of flavonoids and hydroxycinnamic acid were detected using neutral loss (NL) as a survey scan coupled with dependent scans with enhanced product ion (EPI) based on information-dependent acquisition (IDA) criteria. The presented approach is focused on a specific class of molecules and provides comprehensive information on the different conjugation models that are related to specific base molecules, thus allowing a quick and effective identification of all possible combinations, such as mono-, di-, or tri-glycosylation or another type of conjugation such as quinic acid esters.
Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one
Authors: Li Xinnan , Jia Yilin , Li Junda , Zhang Pengfei , Li Tiantian , Lu Li , Yao Hequan , Liu Jie , Zhu Zheying , Xu Jinyi
Published: May 2022

Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.
Innovative Freeze-Dried Snacks with Sodium Alginate and Fruit Pomace (Only Apple or Only Chokeberry) Obtained within the Framework of Sustainable Production
Authors: Ciurzyńska Agnieszka , Popkowicz Paulina , Galus Sabina , Janowicz Monika
Published: May 2022

The aim of the work has been to develop freeze-dried fruit snacks in the form of bars with the use of by-products derived from fruit processing. In effect 14 product designs of fruit gels based on: apple pulp, apple juice, water, sodium alginate and only apple or only chokeberry pomace were prepared. The snacks were freeze-dried. The dry matter content, water activity, structure, colour, mechanical properties, as well as organoleptic evaluation were determined. Freeze-dried bares were obtained according to sustainability production which in this case was relied on application of fruit pomace. The freeze-drying process ensures the microbiological safety of the product without the need to use chemical preservatives. Freeze-dried samples obtained low water activity in the range of 0.099–0.159. The increase in pomace concentration (3–9%) boosted the dry matter content to above 98%, and decreased the brightness of the freeze-dried bars about 6 to 10 units. Mechanical properties varied depending on the product design. With the increase in the amount of pomace, the shear force increased at 23% to 41%. Based on the results, the best variant, that has the most delicate structure and the best organoleptic properties, has proven to contain 1% sodium alginate and 2% pomace.
Facile Preparation of Porous Carbon Derived from Pomelo Peel for Efficient Adsorption of Methylene Blue
Authors: Zhang Wenlin , Liu Mingwan , Zhao Yuhong , Liao Qinhong
Published: May 2022

Pomelo peel waste-derived porous carbon (PPPC) was prepared by a facile one-step ZnCl2 activation method. The preparation parameters of PPPC were the mass ratio of ZnCl2 to pomelo peel of 2:1, carbonization temperature of 500 °C, and carbonization time of 1 h. This obtained PPPC possessed abundant macro-,meso-, and micro-porous structures, and a large specific surface area of 939.4 m2 g−1. Surprisingly, it had excellent adsorption ability for methylene blue, including a high adsorption capacity of 602.4 mg g−1 and good reusability. The adsorption isotherm and kinetic fitted with Langmuir and pseudo-second order kinetic models. This work provides a novel strategy for pomelo peel waste utilization and a potential adsorbent for treating dye wastewater.
Assessment of Chemical Composition and Anti-Penicillium Activity of Vapours of Essential Oils from Abies Alba and Two Melaleuca Species in Food Model Systems
Authors: Valková Veronika , Ďúranová Hana , Vukovic Nenad L. , Vukic Milena , Kluz Maciej , Kačániová Miroslava
Published: May 2022

The possibilities of the practical utilization of essential oils (EOs) from various plant species in the food industry have attracted the attention of the scientific community. Following our previous studies, the antifungal activities of three further commercial EOs, Melaleuca armillaris subsp. armillaris (rosalina; REO), Melaleuca quinquenervia (niaouli; NEO), and Abies alba (fir; FEO), were evaluated in the present research in respect to their chemical profiles, over four different concentrations, 62.5 μL/L, 125 μL/L, 250 μL/L, and 500 μL/L. The findings revealed that the major compounds of REO, NEO, and FEO were linalool (47.5%), 1,8-cineole (40.8%), and α-pinene (25.2%), respectively. In vitro antifungal determinations showed that the inhibition zones of a Penicillium spp. mycelial growth ranged from no inhibitory effectiveness (00.00 ± 00.00 mm) to 16.00 ± 1.00 mm, indicating a very strong antifungal activity which was detected against P. citrinum after the highest REO concentration exposure. Furthermore, the in situ antifungal efficacy of all EOs investigated was shown to be dose-dependent. In this sense, we have found that the highest concentration (500 µL/L) of REO, NEO, and FEO significantly reduced (p < 0.05) the growth of all Penicillium strains inoculated on the bread, carrot, and potato models. These results indicate that the investigated EOs may be promising innovative agents in order to extend the shelf life of different types of food products, such as bread, carrot and potato.
Energy Efficient Access Point Placement for Distributed Massive MIMO
Authors: Zhu Yi-Hang , Callebaut Gilles , Çalık Hatice , Van der Perre Liesbet , Rottenberg François
Published: May 2022

Distributed massive multiple-input multiple-output (D-mMIMO) is one of the key candidate technologies for future wireless networks. A D-mMIMO system has multiple, geographically distributed, access points (APs) jointly serving its users. First of all, this paper reports on where to position these APs to minimize the overall transmit power in actual deployments. As a second contribution, we show that it is essential to take into account both the radiation pattern of the antenna array and the environment information when optimizing AP placement. Neglecting the radiation pattern and environment information, as generally assumed in the literature, can lead to a power penalty in the order of 15 dB and 20 dB, respectively. These results have been obtained by formulating the AP placement optimization problem as a combinatorial optimization problem, which can be solved with different approaches where different channel models are applied. The proposed graph-based channel model drastically lowers the computational time with respect to using an ray-tracing simulator (RTS) for channel evaluation. The performance of the graph-based approach is validated via the RTS, showing that it achieves 5 dB power saving on average compared with a Euclidean distance-based approach, which is the most commonly used approach in the literature.
A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier
Authors: Jin Lilan , Deng Lu , Bartlett Mark , Ren Yiping , Lu Jihong , Chen Qian , Pan Yixiao , Wang Hai , Guo Xiaokui , Liu Chang
Published: May 2022

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.
Sex Differences in Vitamin D Status as a Risk Factor for Incidence of Disability in Instrumental Activities of Daily Living: Evidence from the ELSA Cohort Study
Authors: Luiz Mariane Marques , Máximo Roberta de Oliveira , de Oliveira Dayane Capra , Ramírez Paula Camila , de Souza Aline Fernanda , Delinocente Maicon Luís Bicigo , Steptoe Andrew , de Oliveira Cesar , Alexandre Tiago da Silva
Published: May 2022

Vitamin D deficiency compromises elements underlying the disability process; however, there is no evidence demonstrating the association between vitamin D deficiency and the incidence of disability in instrumental activities of daily living (IADL). We investigated the association between vitamin D deficiency and the risk of incidence of IADL disability separately in men and women. A total of 4768 individuals aged ≥50 years from the English Longitudinal Study of Aging (ELSA) and without IADL disability according to the Lawton scale were available. Vitamin D was evaluated at baseline by serum 25(OH)D concentrations and classified as sufficient (>50 nmol/L), insufficient (>30 to ≤50 nmol/L) or deficient serum (≤30 nmol/L). IADL were reassessed after 4 years. Poisson models stratified by sex and controlled by covariates demonstrated that deficient serum 25(OH)D was a risk factor for the incidence of IADL disability in men (IRR: 1.43; 95% CI 1.02, 2.00), but not in women (IRR: 1.23; 95% CI 0.94, 1.62). Men appear to be more susceptible to the effect of vitamin D deficiency on the incidence of IADL disability, demonstrating the importance of early clinical investigation of serum 25(OH)D concentrations to prevent the onset of disability.
Relationship between Dietary Magnesium Intake and Metabolic Syndrome
Authors: Jiao Yingying , Li Weiyi , Wang Liusen , Jiang Hongru , Wang Shaoshunzi , Jia Xiaofang , Wang Zhihong , Wang Huijun , Zhang Bing , Ding Gangqiang
Published: May 2022

Metabolic syndrome (MetS) is increasingly prevalent, and the relationship between dietary magnesium and MetS remains controversial. Therefore, we aimed to explore the association and dose-response relationship between dietary magnesium intake and MetS and its single component. The sample was adults aged 18 years and above who participated in at least two follow-up surveys in 2009, 2015 and 2018. Food consumption data were collected from three consecutive 24-h dietary recalls. The multivariate Cox proportional risk regression model and restricted cubic spline (RCS) model were used to analyze the association and dose-response relationship between dietary magnesium intake and MetS and its components. In our study, 6104 subjects were included, with a total follow-up of 37,173.36 person-years, and the incidence was 33.16%. Cox regression analysis showed that the multivariable-adjusted Hazard Ratio (HR) for MetS comparing the highest to the lowest quintile of dietary magnesium intake was 0.84 (95% confidence intervals [CI] = 0.71–0.99). Central obesity, elevated TG, elevated blood pressure and elevated blood glucose were reduced by 18%, 41%, 20% and 42%, respectively. The risk of decreased HDL-C was reduced by 23% in the third quintile of dietary magnesium intake, with a slightly increased risk in the highest group. RCS analysis showed that the overall and non-linear associations between dietary magnesium and MetS and its components were statistically significant, the risk of them decreased significantly when magnesium intake was lower than 280 mg/day, and then the curve leveled off or slightly increased.
Neuroprotective Effects of Cranberry Juice Treatment in a Rat Model of Parkinson’s Disease
Authors: Witucki Łukasz , Kurpik Monika , Jakubowski Hieronim , Szulc Michał , Łukasz Mikołajczak Przemysław , Jodynis-Liebert Jadwiga , Kujawska Małgorzata
Published: May 2022

Rich in polyphenols, cranberry juice (CJ) with high antioxidant activity is believed to contribute to various health benefits. However, our knowledge of the neuroprotective potential of cranberries is limited. Previously, we have demonstrated that CJ treatment controls oxidative stress in several organs, with the most evident effect in the brain. In this study, we examined the capability of CJ for protection against Parkinson’s disease (PD) in a rotenone (ROT) rat model. Wistar rats were administered with CJ in a dose of 500 mg/kg b.w./day (i.g.) and subcutaneously injected with ROT (1.3 mg/kg b.w./day). The experiment lasted 45 days, including 10 days pre-treatment with CJ and 35 days combined treatment with CJ and ROT. We quantified the expression of α-synuclein and apoptosis markers in the midbrain, performed microscopic examination, and assessed postural instability to evaluate the CJ neuroprotective effect. Our results indicate that the juice treatment provided neuroprotection, as evidenced by declined α-synuclein accumulation, Bax and cleaved/active caspase-9 expression, and normalized cytochrome c level that was accompanied by the enhancement of neuronal activity survival and improved postural instability. Importantly, we also found that long-term administration of CJ alone in a relatively high dose may exert a deleterious effect on cell survival in the midbrain.
Secular Trends in Time-of-Day of Energy Intake in a Chinese Cohort
Authors: Song Xiaoyun , Wang Huijun , Su Chang , Wang Zhihong , Zhang Jiguo , Ding Gangqiang , Zhang Bing
Published: May 2022

Few studies have described the status and change of time-of-day of energy intake on a population level. This study aims to investigate the secular trend in time-of-day of energy intake using a Chinese cohort, and to examine demographic disparities in trends. A total of 20,976 adults with at least two waves of dietary data in the China Health and Nutrition Survey (CHNS 1991–2018) were included. A multilevel linear mixed model was applied to the energy proportions of breakfast, lunch and dinner. A multilevel Tobit regression model was applied to the energy proportion of morning snack, afternoon snack and evening snack. Time-demographic interaction terms were tested to examine demographic disparities in the trends. From 1991 to 2018, the marginal mean of the energy proportion of breakfast experienced first a falling and then a rising trend, and the marginal mean of energy proportions of lunch and dinner both presented first a rising and then a falling trend. The marginal means of all snacks took on a rising trend. Significant time-demographic interactions were observed for energy proportion of each eating occasion. On average, female, older and rural people tended to have a higher energy proportion at breakfast and lower energy proportion at lunch and dinner. Female, younger and urban people tended to have higher snack energy proportions. The time-of-day of energy intake has first shifted towards later in the day and then towards a balanced meal pattern in this Chinese cohort. Demographic disparities were observed in both the secular trend and the mean level of energy proportions of eating occasions. The health implications of such meal patterns warrant further investigation.
Ripe Tomato Saponin Esculeoside A and Sapogenol Esculeogenin A Suppress CD4+ T Lymphocyte Activation by Modulation of Th2/Th1/Treg Differentiation
Authors: Zhou Jian-Rong , Yamada Rie , Huruiti Erina , Kitahara Nozomi , Nakamura Honami , Fang Jun , Nohara Toshihiro , Yokomizo Kazumi
Published: May 2022

We report that esculeoside A (EsA), a glycoside and a major component in ripe tomato fruit, ameliorated experimental dermatitis in mice. However, the underlying immunologic molecular mechanisms are unknown. The present study examined its underlying immune nutrition mechanism using concanavalin A (ConA)-blast mouse splenocyte primary culture. We found that EsA and its sapogenol esculeogenin A (Esg-A) concentration-dependently suppressed T-lymphoproliferation using CFSE-labeled flow-cytometry and water-soluble tetrazolium (WST) assay. Using ELISA and q-PCR methods, EsA/Esg-A showed profound decreases in T helper 2 (Th2)-relevant interleukin-4 (IL-4) secretion and mRNA expression, and GATA3 expression. Moreover, EsA/Esg-A suppressed CD4+ T-lymphocyte activation by decreasing IL-2 secretion and mRNA expression and CD25+ cell proportion. Further, EsA/Esg-A alleviated Treg suppressive activity by reducing IL-10 secretion, Foxp3 mRNA expression, and cell numbers. We suggest the immune nutrition function by tomato component, and highlight that EsA/Esg-A are capable of reducing CD4+ T-lymphocyte activation via a reduction in Th2-lymphocyte activity by modulation of Th2/Th1/Treg subunit differentiation.
Ginkgo Biloba Leaf Extract Improves an Innate Immune Response of Peripheral Blood Leukocytes of Alzheimer’s Disease Patients
Authors: Sochocka Marta , Ochnik Michał , Sobczyński Maciej , Gębura Katarzyna , Zambrowicz Aleksandra , Naporowski Piotr , Leszek Jerzy
Published: May 2022

Background: One of the main features of Alzheimer’s disease (AD) pathology is failure in innate immune response and chronic inflammation. Lack of effective AD treatment means that more attention is paid to alternative therapy and drugs of natural origin, such as extract of Ginkgo biloba (EGb). The purpose of this study was to investigate the effect of EGb on the mechanisms of innate immune response of peripheral blood leukocytes (PBLs) in AD patients. Methods: In AD patients and healthy-age matched controls, the effect of EGb on two of innate immune reactions, i.e., PBLs resistance to viral infection ex vivo and production of cytokines, namely TNF-α, IFN-γ, IL-1β, IL-10, IL-15, and IFN-α, were investigated. The influence of EGb on inflammatory-associated genes expression that regulate innate immune response to viral infection and cytokine production, namely IRF-3, IRF-7, tetherin, SOCS1, SOCS3, NFKB1, p65, and MxA was also examined. Results: A beneficial effect of EGb especially in AD women was observed. EGb decreased production of TNF-α, IFN-γ, and IL-10 and increased IL-15 and IL-1β. The effect was more pronouncement in AD group. EGb also downregulated expression of investigated genes. Conclusions: EGb may have an advantageous properties for health management in elderly and AD sufferers but especially in women with AD. Improving peripheral innate immune cells’ activity by adding EGb as accompanying treatment in AD may be, in the long term, a good course to modify the disease progression.
Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance Breath Test Results
Authors: Schnedl Wolfgang J. , Meier-Allard Nathalie , Michaelis Simon , Lackner Sonja , Enko Dietmar , Mangge Harald , Holasek Sandra J.
Published: May 2022

Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the Kruskal Wallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests.
Prevention of HBV Reactivation in Hemato-Oncologic Setting during COVID-19
Authors: Sagnelli Caterina , Sica Antonello , Creta Massimiliano , Borsetti Alessandra , Ciccozzi Massimo , Sagnelli Evangelista
Published: May 2022

Onco-hematologic patients are highly susceptible to SARS-CoV-2 infection and, once infected, frequently develop COVID-19 due to the immunosuppression caused by tumor growth, chemotherapy and immunosuppressive therapy. In addition, COVID-19 has also been recognized as a further cause of HBV reactivation, since its treatment includes the administration of corticosteroids and some immunosuppressive drugs. Consequently, onco-hematologic patients should undergo SARS-CoV-2 vaccination and comply with the rules imposed by lockdowns or other forms of social distancing. Furthermore, onco-hematologic facilities should be adapted to new needs and provided with numerically adequate health personnel vaccinated against SARS-CoV-2 infection. Onco-hematologic patients, both HBsAg-positive and HBsAg-negative/HBcAb-positive, may develop HBV reactivation, made possible by the support of the covalently closed circular DNA (cccDNA) persisting in the hepatocytic nuclei of patients with an ongoing or past HBV infection. This occurrence must be prevented by administering high genetic barrier HBV nucleo(t)side analogues before and throughout the antineoplastic treatment, and then during a long-term post-treatment follow up. The prevention of HBV reactivation during the SARS-CoV-2 pandemic is the topic of this narrative review.
Colorimetric Kit for Rapid Porcine Circovirus 2 (PCV-2) Diagnosis
Authors: Basso Caroline Rodrigues , Yamakawa Ana Carolina , Cruz Taís Fukuta , Pedrosa Valber Albuquerque , Magro Massimiliano , Vianello Fabio , Araújo Júnior João Pessoa
Published: May 2022

The aim of the current study is to present a low-cost and easy-to-interpret colorimetric kit used to diagnose porcine circovirus 2 (PCV-2) to the naked eye, without any specific equipment. The aforementioned kit used as base hybrid nanoparticles resulting from the merge of surface active maghemite nanoparticles and gold nanoparticles, based on the deposition of specific PCV-2 antibodies on their surface through covalent bonds. In total, 10 negative and 40 positive samples (≥102 DNA copies/µL of serum) confirmed by qPCR technique were tested. PCV-1 virus, adenovirus, and parvovirus samples were tested as interferents to rule out likely false-positive results. Positive samples showed purple color when they were added to the complex, whereas negative samples showed red color; they were visible to the naked eye. The entire color-change process took place approximately 1 min after the analyzed samples were added to the complex. They were tested at different dilutions, namely pure, 1:10, 1:100, 1:1000, and 1:10,000. Localized surface plasmon resonance (LSPR) and transmission electron microscopy (TEM) images were generated to validate the experiment. This new real-time PCV-2 diagnostic methodology emerged as simple and economic alternative to traditional tests since the final price of the kit is USD 4.00.
Mangifera indica ‘Namdokmai’ Prevents Neuronal Cells from Amyloid Peptide Toxicity and Inhibits BACE-1 Activities in a Drosophila Model of Alzheimer’s Amyloidosis
Authors: Temviriyanukul Piya , Kittibunchakul Suwapat , Trisonthi Piyapat , Kunkeaw Thanit , Inthachat Woorawee , Siriwan Dalad , Suttisansanee Uthaiwan
Published: May 2022

Alzheimer’s disease (AD) is a progressive neurological illness with few effective treatments. Thus, ameliorating the effects of AD using natural products has attracted global attention with promising efficacy and safety. In this study, ten tropical fruits including Ananas comosus ‘Phulae’, Ananas comosus ‘Pattavia’, Carica papaya ‘Khaekdum’, Carica papaya ‘Khaeknuan’, Durio zibethinus ‘Monthong’, Durio zibethinus ‘Chanee’, Psidium guajava ‘Kimju’, Psidium guajava ‘Keenok’, Mangifera indica ‘Kaew’ and Mangifera indica ‘Namdokmai’ were screened for their inhibitory activities against the key enzymes, cholinesterases and β-secretase (BACE-1), involved in AD pathogenesis. The top three fruit extracts with promising in vitro anti-AD activities were further investigated using rat pheochromocytoma PC-12 neuronal cell line and Drosophila AD model. Data showed that M. indica ‘Kaew’, M. indica ‘Namdokmai’ and P. guajava ‘Kimju’ reduced Aβ1–42-mediated neurotoxicity by promoting glutathione-dependent enzymes, while M. indica ‘Namdokmai’ limited Aβ1–42 peptide formation via BACE-1 inhibition and amended locomotory behavior of the Drosophila AD model. Results indicated the potential anti-AD properties of tropical fruits, particularly M. indica ‘Namdokmai’ in the prevention of Aβ1–42-mediated neurotoxicity and as a BACE-1 blocker.
Targeting the Hematopoietic Stem Cell Niche in β-Thalassemia and Sickle Cell Disease
Authors: Aprile Annamaria , Sighinolfi Silvia , Raggi Laura , Ferrari Giuliana
Published: May 2022

In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality and engraftment of HSCs depend on the BM microenvironment, influencing the outcome of HSC transplantation (HSCT) both in allogeneic and in autologous gene therapy settings. In BThal and SCD, the consequences of severe anemia alter erythropoiesis and cause chronic stress in different organs, including the BM. Here, we discuss the recent findings that highlighted multiple alterations of the BM niche in BThal and SCD. We point out the importance of improving our understanding of HSC biology, the status of the BM niche, and their functional crosstalk in these disorders towards the novel concept of combined therapies by not only targeting the genetic defect, but also key players of the HSC–niche interaction in order to improve the clinical outcomes of transplantation.
Population Pharmacokinetics and Dosing Regimen Optimization of Latamoxef in Chinese Children
Authors: Wang Yang , Sun Dan , Mei Yan , Wu Sanlan , Li Xinlin , Li Sichan , Wang Jun , Gao Liuliu , Xu Hua , Tuo Yali
Published: May 2022

The present study aimed to establish population pharmacokinetic models of latamoxef, as well as its R- and S-epimers, and generate findings to guide the individualized administration of latamoxef in pediatric patients. A total of 145 in-hospital children aged 0.08–10.58 years old were included in this study. Three population pharmacokinetic models of latamoxef and its R- and S-epimers were established. The stability and predictive ability of the final models were evaluated by utilizing goodness-of-fit plots, nonparametric bootstrapping, and normalized prediction distribution errors. The final model of total latamoxef was considered as a basis for the dosing regimen. A two-compartment model with first-order elimination best described the pharmacokinetics of total latamoxef. The population typical values of total latamoxef were as follows: central compartment distribution volume (V1) of 4.84 L, peripheral compartment distribution volume (V2) of 16.18 L, clearance (CL) of 1.00 L/h, and inter-compartmental clearance (Q) of 0.97 L/h. Moreover, R-epimer has a higher apparent volume of distribution and lower clearance than S-epimer. Body surface area (BSA) was identified as the most significant covariate to V, CL, and Q. Specific recommendations are given for dosage adjustment in pediatric patients based on BSA. This study highlights that a BSA-normalized dose of latamoxef was required when treating different bacteria to reach the therapeutic target more effectively.
A Small Peptide Increases Drug Delivery in Human Melanoma Cells
Authors: Tong Shirley , Darwish Shaban , Ariani Hanieh Hossein Nejad , Lozada Kate Alison , Salehi David , Cinelli Maris A. , Silverman Richard B. , Kaur Kamaljit , Yang Sun
Published: May 2022

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa KK-11 significantly increased the stability of the peptide, with 45.3% remaining detectable after 24 h with human serum incubation. Co-treatment of KK-11 with doxorubicin was found to significantly enhance the cytotoxicity of doxorubicin compared to doxorubicin alone, or sequential KK-11 and doxorubicin treatment. In vivo and ex vivo imaging revealed that D-aa KK-11 distributed to xenografted A375 melanoma tumors as early as 5 min and persisted up to 24 h post tail vein injection. When co-administered, D-aa KK-11 significantly enhanced the anti-tumor activity of a novel nNOS inhibitor (MAC-3-190) in an A375 human melanoma xenograft mouse model compared to MAC-3-190 treatment alone. No apparent systemic toxicities were observed. Taken together, these results suggest that KK-11 may be a promising human melanoma-targeted delivery vector for anti-melanoma cargo.
Click-Chemistry Cross-Linking of Hyaluronan Graft Copolymers
Authors: Saletti Mario , Paolino Marco , Ballerini Lavinia , Giuliani Germano , Leone Gemma , Lamponi Stefania , Andreassi Marco , Bonechi Claudia , Donati Alessandro , Piovani Daniele , Schieroni Alberto Giacometti , Magnani Agnese , Cappelli Andrea
Published: May 2022

An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields.
3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity
Authors: Ding Huifen , Jambunathan Kalyani , Jiang Guochun , Margolis David M. , Leng Iris , Ihnat Michael , Ma Jian-Xing , Mirsalis Jon , Zhang Yuanyuan
Published: May 2022

Mitochondrial toxicity (Mito-Tox) risk has increased due to the administration of several classes of drugs, particularly some life-long antiretroviral drugs for HIV+ individuals. However, no suitable in vitro assays are available to test long-term Mito-Tox (≥4 weeks). The goal of this study is to develop a 3D spheroid system of human primary urine-derived stem cells (USC) for the prediction of drug-induced delayed Mito-Tox. The cytotoxicity and Mito-Tox were assessed in 3D USC spheroids 4 weeks after treatment with antiretroviral drugs: zalcitabine (ddC; 0.1, 1 and 10 µM), tenofovir (TFV; 3, 30 and 300 µM) or Raltegravir (RAL; 2, 20 and 200 µM). Rotenone (RTNN, 10 µM) and 0.1% DMSO served as positive and negative controls. Despite only mild cytotoxicity, ddC significantly inhibited the expression of oxidative phosphorylation enzyme Complexes I, III, and IV; and RAL transiently reduced the level of Complex IV. A significant increase in caspase 3 and ROS/RNS level but a decrease in total ATP were observed in USC treated with ddC, TFV, RAL, and RTNN. Levels of mtDNA content and mitochondrial mass were decreased in ddC but minimally or not in TFV- and RAL-treated spheroids. Thus, 3D USC spheroid using antiretroviral drugs as a model offers an alternative platform to assess drug-induced late Mito-Tox.
Chitooligosaccharides Improve the Efficacy of Checkpoint Inhibitors in a Mouse Model of Lung Cancer
Authors: Johansen Astrid Zedlitz , Carretta Marco , Thorseth Marie-Louise , Khan Shawez , Fjæstad Klaire Yixin , Brøchner Christian Beltoft , Linder Hannes , Ankjærgaard Christina , Donia Marco , Chen Inna , Nielsen Dorte Lisbet , Behrens Claus Preibisch , Madsen Daniel Hargbøl
Published: May 2022

YKL-40 (also named chitinase 3 like-1 protein [CHI3L1]) is a secreted chitinase-like protein which is upregulated in cancers and suggested to have pro-tumorigenic activity. YKL-40 lacks enzymatic function, but it can bind carbohydrates such as chitin. Chitooligosaccharides (COS) derived from deacetylation and hydrolysis of chitin might be used for the blockade of YKL-40 function. Here, public single-cell RNA sequencing datasets were used to elucidate the cellular source of YKL-40 gene expression in human tumors. Fibroblasts and myeloid cells were the primary sources of YKL-40. Screening of YKL-40 gene expression in syngeneic mouse cancer models showed the highest expression in the Lewis lung carcinoma (LL2) model. LL2 was used to investigate COS monotherapy and combinations with immune checkpoint inhibitors (anti-PD-L1 and anti-CTLA-4) (ICIs) and radiotherapy (8 Gy × 3) (RT). COS tended to reduce plasma YKL-40 levels, but it did not affect tumor growth. LL2 showed minimal responses to ICIs, or to RT alone. Interestingly, ICIs combined with COS led to delayed tumor growth. RT also enhanced the efficacy of ICIs; however, the addition of COS did not further delay the tumor growth. COS may exert their anti-tumorigenic effects through the inhibition of YKL-40, but additional functions of COS should be investigated.
Transcranial Photobiomodulation Therapy for Sexual Dysfunction Associated with Depression or Induced by Antidepressant Medications
Authors: Salehpour Farzad , Khademi Mahsa , Vahedifard Farzan , Cassano Paolo
Published: May 2022

Sexual dysfunction (SD) is frequently encountered in patients suffering from depression. There is a bidirectional relationship between various types of SD and depression, so the presence or treatment of one condition may exacerbate or improve the other condition. The most frequent sexual problem in untreated depressed patients is declining sexual desire, while in treated depressed patients it is difficulties with erection/ejaculation and with orgasm. Numerous classes of neuropsychiatric medications, commonly used in depressed patients—such as antidepressant, antipsychotic, alpha sympathetic, and opioid drugs—may cause SD. Photobiomodulation (PBM) therapy, also called low-level light/laser therapy, is a novel neuromodulation technique for neuropsychiatric conditions, such as depression. Transcranial PBM (tPBM) targets the cellular metabolism—through the mitochondrial respiratory enzyme, cytochrome c oxidase—and has numerous cellular and physiological beneficial effects on the central nervous system. This paper represents a comprehensive review of the application of tPBM to SD, coexisting with depression or induced by antidepressant medications.