bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanotechnology-Based Bioactive Antifeedant for Plant Protection
Authors: Melanie Melanie , Miranti Mia , Kasmara Hikmat , Malini Desak Made , Husodo Teguh , Panatarani Camellia , Joni I Made , Hermawan Wawan
Published: February 2022

The productivity of vegetable crops is constrained by insect pests. The search for alternative insect pest control is becoming increasingly important and is including the use of plant-derived pesticides. Plant-derived pesticides are reported as effective in controlling various insect pests through natural mechanisms, with biodegradable organic materials, diverse bioactivity, and low toxicity to non-target organisms. An antifeedant approach for insect control in crop management has been comprehensively studied by many researchers, though it has only been restricted to plant-based compounds and to the laboratory level at least. Nano-delivery formulations of biopesticides offer a wide variety of benefits, including increased effectiveness and efficiency (well-dispersion, wettability, and target delivery) with the improved properties of the antifeedant. This review paper evaluates the role of the nano-delivery system in antifeedant obtained from various plant extracts. The evaluation includes the research progress of antifeedant-based nano-delivery systems and the bioactivity performances of different types of nano-carrier formulations against various insect pests. An antifeedant nano-delivery system can increase their bioactivities, such as increasing sublethal bioactivity or reducing toxicity levels in both crude extracts/essential oils (EOs) and pure compounds. However, the plant-based antifeedant requires nanotechnological development to improve the nano-delivery systems regarding properties related to the bioactive functionality and the target site of insect pests. It is highlighted that the formulation of plant extracts creates a forthcoming insight for a field-scale application of this nano-delivery antifeedant due to the possible economic production process.
Crystallization and Electrical Properties of Ge-Rich GeSbTe Alloys
Authors: Cecchi Stefano , Lopez Garcia Iñaki , Mio Antonio M. , Zallo Eugenio , Abou El Kheir Omar , Calarco Raffaella , Bernasconi Marco , Nicotra Giuseppe , Privitera Stefania M. S.
Published: February 2022

Enrichment of GeSbTe alloys with germanium has been proposed as a valid approach to increase the crystallization temperature and therefore to address high-temperature applications of non-volatile phase change memories, such as embedded or automotive applications. However, the tendency of Ge-rich GeSbTe alloys to decompose with the segregation of pure Ge still calls for investigations on the basic mechanisms leading to element diffusion and compositional variations. With the purpose of identifying some possible routes to limit the Ge segregation, in this study, we investigate Ge-rich Sb2Te3 and Ge-rich Ge2Sb2Te5 with low (<40 at %) or high (>40 at %) amounts of Ge. The formation of the crystalline phases has been followed as a function of annealing temperature by X-ray diffraction. The temperature dependence of electrical properties has been evaluated by in situ resistance measurements upon annealing up to 300 °C. The segregation and decomposition processes have been studied by scanning transmission electron microscopy (STEM) and discussed on the basis of density functional theory calculations. Among the studied compositions, Ge-rich Ge2Sb2Te5 is found to be less prone to decompose with Ge segregation.
Instantaneous Property Prediction and Inverse Design of Plasmonic Nanostructures Using Machine Learning: Current Applications and Future Directions
Authors: Xu Xinkai , Aggarwal Dipesh , Shankar Karthik
Published: February 2022

Advances in plasmonic materials and devices have given rise to a variety of applications in photocatalysis, microscopy, nanophotonics, and metastructures. With the advent of computing power and artificial neural networks, the characterization and design process of plasmonic nanostructures can be significantly accelerated using machine learning as opposed to conventional FDTD simulations. The machine learning (ML) based methods can not only perform with high accuracy and return optical spectra and optimal design parameters, but also maintain a stable high computing efficiency without being affected by the structural complexity. This work reviews the prominent ML methods involved in forward simulation and inverse design of plasmonic nanomaterials, such as Convolutional Neural Networks, Generative Adversarial Networks, Genetic Algorithms and Encoder–Decoder Networks. Moreover, we acknowledge the current limitations of ML methods in the context of plasmonics and provide perspectives on future research directions.
Cytotoxicity and Genotoxicity of Nanomaterials
Authors: Valdiglesias Vanessa
Published: February 2022

Nanomaterials (NMs) are of significant relevance due to their unique physicochemical properties, which have been extensively exploited for widespread applications in human healthcare and consumer goods, such as cosmetics and textiles [...]
Eating Speed Is Associated with the Presence of Sarcopenia in Older Patients with Type 2 Diabetes: A Cross-Sectional Study of the KAMOGAWA-DM Cohort
Authors: Hashimoto Yoshitaka , Takahashi Fuyuko , Kaji Ayumi , Sakai Ryosuke , Okamura Takuro , Kitagawa Noriyuki , Okada Hiroshi , Nakanishi Naoko , Majima Saori , Senmaru Takafumi , Ushigome Emi , Asano Mai , Hamaguchi Masahide , Yamazaki Masahiro , Fukui Michiaki
Published: February 2022

To determine the relationship between eating speed and the presence of sarcopenia in older patients with type 2 diabetes (T2D), in this cross-sectional study, patient eating speeds were classified as “fast-”, “normal-” and “slow-speed eating.” A multifrequency impedance analyzer was used to evaluate patient body compositions. Sarcopenia was defined as having both low muscle strength, a handgrip strength <28 kg for men and <18 kg for women, and low skeletal muscle mass as a skeletal muscle mass index <7.0 kg/m2 for men and <5.7 kg/m2 for women. Among 239 individuals, the frequencies of fast-, normal-, and slow-speed eating were 47.3%, 32.2%, and 20.5%, respectively; and the prevalence of sarcopenia was 15.9%. Patients with a slow eating speed had greater prevalence of low skeletal muscle mass, low muscle strength, and sarcopenia than those with a fast or normal eating speed. After adjusting for covariates, compared to slow eaters, the odds ratio of having sarcopenia among fast- and normal-speed eaters was 0.31 [95% CI: 0.12–0.80] and 0.18 [95% CI: 0.06–0.53], respectively. Having a slow eating speed is associated with a heightened risk of sarcopenia in older patients with T2D.
Beneficial Effects of Partly Milled Highland Barley on the Prevention of High-Fat Diet-Induced Glycometabolic Disorder and the Modulation of Gut Microbiota in Mice
Authors: Li Siqi , Wang Mengqian , Li Chang , Meng Qingjia , Meng Yantong , Ying Jian , Bai Shuqun , Shen Qun , Xue Yong
Published: February 2022

The nutritional functions of highland barley (HB) are superior to those of regular cereals and have attracted increasing attention in recent years. The objective of this study was to investigate whether partly milled highland barley (PHB) can regulate the serum glucose and lipid disorders of mice fed a high-fat diet (HFD) and to further explore their potential gut microbiota modulatory effect. Our results showed that PHB supplementation significantly reduced fasting blood glucose (FBG) and improved oral glucose tolerance. Histological observations confirmed the ability of PHB to alleviate liver and intestine damage. Furthermore, the results of 16S amplicon sequencing revealed that PHB prevented a HFD-induced gut microbiota dysbiosis, enriching some beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Ileibacterium, and reducing several HFD-dependent taxa (norank_f_Desulfovibrionaceae, Blautia, norank_f_Lachnospiraceae, unclassified_f_Lachnospiraceae, and Colidextribacter). In addition, the increase of Lactobacillus and Bifidobacterium presence has a slightly dose-dependent relationship with the amount of the added PHB. Spearman correlation analysis revealed that Lactobacillus and Bifidobacterium were negatively correlated with the blood glucose level of the oral glucose tolerance test. Overall, our results provide important information about the processing of highland barley to retain its hypoglycemic effect and improve its acceptability and biosafety.
Pasteurized Akkermansia muciniphila Ameliorate the LPS-Induced Intestinal Barrier Dysfunction via Modulating AMPK and NF-κB through TLR2 in Caco-2 Cells
Authors: Shi Mengxuan , Yue Yunshuang , Ma Chen , Dong Li , Chen Fang
Published: February 2022

Akkermansia muciniphila is well known for the amelioration of inflammatory responses and restoration of intestinal barrier function. The beneficial effect of A. muciniphila occurred through contacting Toll-like receptor 2 (TLR2) on intestinal epithelial cells by wall components. In this case, the downstream mechanism of pasteurized A. muciniphila stimulating TLR2 for ameliorated intestinal barrier function is worth investigating. In this study, we evaluated the effect of live and pasteurized A. muciniphila on protecting the barrier dysfunction of Caco-2 intestinal epithelial cells induced by lipopolysaccharide (LPS). We discovered that both live and pasteurized A. muciniphila could attenuate an inflammatory response and improve intestinal barrier integrity in Caco-2 monolayers. We demonstrated that A. muciniphila enhances AMP-activated protein kinase (AMPK) activation and inhibits Nuclear Factor-Kappa B (NF-κB) activation through the stimulation of TLR2. Overall, we provided a specific mechanism for the probiotic effect of A. muciniphila on the intestinal barrier function of Caco-2 cells.
Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats
Authors: Rodríguez Romina M. , Cortés-Espinar Antonio J. , Soliz-Rueda Jorge R. , Feillet-Coudray Christine , Casas François , Colom-Pellicer Marina , Aragonès Gerard , Avila-Román Javier , Muguerza Begoña , Mulero Miquel , Salvadó Maria Josepa
Published: February 2022

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to “standard”, “cafeteria” and “cafeteria diet + GSPE” treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.
Preliminary Report on Intestinal Flora Disorder, Faecal Short-Chain Fatty Acid Level Decline and Intestinal Mucosal Tissue Weakening Caused by Litchi Extract to Induce Systemic Inflammation in HFA Mice
Authors: Sun Dongfang , Wang Chen , Sun Lijun , Hu Lianhua , Fang Zhijia , Deng Qi , Zhao Jian , Gooneratne Ravi
Published: February 2022

Certain foods are known as “heating” foods in Chinese medicine. Over-consumption of these foods can lead to symptoms known as “heating up”. These symptoms have been shown to be symptoms of systemic low-grade inflammation. However, the mechanism by which these foods cause inflammation is not clear. In this preliminary study, we investigated dysbacteriosis of the gut microbiota as a possible cause of inflammation by litchi, a typical “heating” food. A human flora-associated (HFA) mouse model (donor: n = 1) was constructed. After gavaging the mice with litchi extract suspension at low, medium and high doses (400, 800, 1600 mg/kg·d−1, respectively) (n = 3) for 7 days, the serum levels of inflammatory cytokines, gut microbiota, the concentration of SCFAs and the integrity of the intestinal mucosal barrier were measured. The results revealed significant increases in the abundance of Prevotella and Bacteroides. A significant increase in the abundance of Bilophila and a decrease in Megasomonas was observed in the high-dose group. High-dose litchi intervention led to a decrease of most SCFA levels in the intestine. It also caused a more than two-fold increase in the serum TNF-α level and LPS level but a decrease in the IL-1β and IL-6 levels. Medium- and high-dose litchi intervention caused widening of the intestinal epithelial cell junction complex and general weakening of the intestinal mucosal barrier as well as reduced energy conversion efficiency of the gut microbiota. These data suggest that litchi, when consumed excessively, can lead to a low degree of systematic inflammation and this is linked to its ability to cause dysbacteriosis of the gut microbiota, decrease SCFAs and weaken the intestinal mucosal tissues.
Effects of Zn-Enriched Bifidobacterium longum on the Growth and Reproduction of Rats
Authors: Han Xinran , Liu Fei , Zhang Qiuxiang , Mao Bingyong , Tang Xin , Huang Jie , Guo Renmei , Zhao Jianxin , Zhang Hao , Cui Shumao , Chen Wei
Published: February 2022

Zn is an essential trace element required for maintaining normal growth and development. Zn deficiency can cause growth retardation and reproductive system dysplasia, while Zn supplementation for treating Zn deficiency requires the use of high-quality Zn preparations. In this study, Bifidobacterium longum CCFM1195 was screened for its high Zn enrichment capacity, and the effects of different Zn supplementation regimens and doses on the growth and development of rats after Zn supplementation were investigated by supplementing Zn-deficient rat pups with different doses of various Zn supplements (ZnO, CCFM1195 + ZnO, and Zn-enriched CCFM1195). It was shown that the bioavailability of Zn was positively correlated with indicators of recovery after Zn supplementation, with Zn-enriched CCFM1195 having the best effect, followed by CCFM1195 + ZnO, while ZnO had the worst effect. Significant differences were also observed between the gut microbiota of control, model, and Zn-supplemented rats. Overall, administration of Zn-enriched CCFM1195 was more effective than the other approaches in restoring physical indicators of Zn deficiency after Zn supplementation, and this advantage was more significant at low-dose Zn supplementation.
Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice
Authors: Nguyen Long T. , Larkin Benjamin P. , Wang Rosy , Faiz Alen , Pollock Carol A. , Saad Sonia
Published: February 2022

Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild–moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease’s prognostication.
Cancer Cell Inhibiting Sea Cucumber (Holothuria leucospilota) Protein as a Novel Anti-Cancer Drug
Authors: Ru Ruizhen , Guo Yanzheng , Mao Juanxuan , Yu Zonghe , Huang Wen , Cao Xudong , Hu Huijian , Meng Minjie , Yuan Lihong
Published: February 2022

Cancer remains the primary cause of death worldwide. To develop less toxic anti-cancer drugs to relieve the suffering and improve the survival of cancer patients is the major focus in the anti-cancer field. To this end, marine creatures are being extensively studied for their anti-cancer effects, since extracts from at least 10% of the marine organisms have been shown to possess anti-tumor activities. As a classic Chinese traditional medicine, sea cucumbers and compounds extracted from the sea cucumbers, such as polysaccharides and saponins, have recently been shown to exhibit anti-cancer, anti-inflammatory, and anti-oxidant effects. Holothuria leucospilota (H. leucospilota) is a tropical edible sea cucumber species that has been successfully cultivated and farmed in large scales, providing a readily available source of raw materials to support the development of novel marine anti-cancer drugs. However, very few studies have so far been performed on the biological activities of H. leucospilota. In this study, we first investigated the anti-cancer effect of H. leucospilota protein on three cancer cell lines (i.e., HepG2, A549, Panc02) and three normal cell lines (NIH-3T3, HaCaT, 16HBE). Our data showed that H. leucospilota protein decreased the cell viabilities of HepG2, A549, HaCaT, 16HBE in a concentration-dependent manner, while Panc02 and NIH-3T3 in a time- and concentration-dependent manner. We also found that the inhibitory effect of H. leucospilota protein (≥10 μg/mL) on cell viability is near or even superior to EPI, a clinical chemotherapeutic agent. In addition, our data also demonstrated that H. leucospilota protein significantly affected the cell cycle and induced apoptosis in the three cancer cell lines investigated; in comparison, it showed no effects on the normal cell lines (i.e., NIH-3T3, HaCaT and 16HBE). Finally, our results also showed that H. leucospilota protein exhibited the excellent performance in inhibiting cell immigrations. In conclusion, H. leucospilota protein targeted the cancer cell cycles and induced cancer cell apoptosis; its superiority to inhibit cancer cell migration compared with EPI, shows the potential as a promising anti-cancer drug.
Food Security, Dietary Diversity, Dietary Patterns and the Double Burden of Malnutrition among School-Aged Children and Adolescents in Two Nigerian States
Authors: Adeomi Adeleye Abiodun , Fatusi Adesegun , Klipstein-Grobusch Kerstin
Published: February 2022

Background: Little evidence exists on the relationship between diet-related factors and child/adolescent malnutrition in Nigeria. This study aimed to assess the associations between household food insecurity (HFI), dietary diversity (DD), and dietary patterns (DP) with the double burden of malnutrition (DBM) among 6–19-year-olds in two Nigerian States. Methods: This community-based cross-sectional study was carried out among 1200 respondents (6–19 years in age) in the Gombe and Osun States of Nigeria. HFI was assessed using the HFI access scale. DD was assessed using a 24-h dietary recall. DP were determined by principal component analysis using a 30-day food frequency questionnaire. DP scores were categorized into quartiles (Q) for statistical analysis. Diet-related predictors of DBM were assessed using logistic regression. Results: HFI was experienced by 568 (47.3%) respondents. The median DD score was 7.0 (maximum of 14). Two DPs were identified, diversified DP (DDP) and traditional DP (TDP). TDP was significantly associated with both thinness (Q4:OR: 2.91; 95% CI: 1.52–5.55; Ptrend: 0.002) and overweight/obesity (Q4:OR: 2.50; 95% CI: 1.43–4.35; Ptrend: 0.007), while DDP was inversely related with thinness (Q4:OR: 0.36; 95% CI: 0.21–0.61; Ptrend: 0.008) as compared to Q1. Conclusions: TDP increased the odds for DBM, while the DDP reduced the odds.
Route of Sensitization to Peanut Influences Immune Cell Recruitment at Various Mucosal Sites in Mouse: An Integrative Analysis
Authors: Briard Mélanie , Guinot Marine , Grauso Marta , Guillon Blanche , Hazebrouck Stéphane , Bernard Hervé , Bouchaud Grégory , Michel Marie-Laure , Adel-Patient Karine
Published: February 2022

Symptom occurrence at the first ingestion suggests that food allergy may result from earlier sensitization via non-oral routes. We aimed to characterize the cellular populations recruited at various mucosal and immune sites after experimental sensitization though different routes. BALB/cJ mice were exposed to a major allergenic food (peanut) mixed with cholera toxin via the intra-gastric (i.g.), respiratory, cutaneous, or intra-peritoneal (i.p.) route. We assessed sensitization and elicitation of the allergic reaction and frequencies of T cells, innate lymphoid cells (ILC), and inflammatory and dendritic cells (DC) in broncho-alveolar lavages (BAL), lungs, skin, intestine, and various lymph nodes. All cellular data were analyzed through non-supervised and supervised uni/multivariate analysis. All exposure routes, except cutaneous, induced sensitization, but intestinal allergy was induced only in i.g.- and i.p.-exposed mice. Multivariate analysis of all cellular constituents did not discriminate i.g. from control mice. Conversely, respiratory-sensitized mice constituted a distinct cluster, characterized by high local inflammation and immune cells recruitment. Those mice also evidenced changes in ILC frequencies at distant site (intestine). Despite absence of sensitization, cutaneous-exposed mice evidenced comparable changes, albeit less intense. Our study highlights that the initial route of sensitization to a food allergen influences the nature of the immune responses at various mucosal sites. Interconnections of mucosal immune systems may participate in the complexity of clinical manifestations as well as in the atopic march.
A Dose–Response Relationship of Alcohol Consumption with Risk of Visual Impairment in Korean Adults: The Kangbuk Samsung Health Study
Authors: Han So Young , Chang Yoosoo , Kim Yejin , Choi Chul Young , Ryu Seungho
Published: February 2022

Visual impairment is a global health problem that leads to poor quality of life. The aim of the study was to examine the dose–response relationship between alcohol consumption and incident visual impairment (VI). This longitudinal cohort study consisted of 287,352 Korean adults who attended health screenings between March 2011 and December 2017 and were followed for up to 8.8 years (median, 4.9 years). Participants were categorized based on their average alcohol consumption. VI was defined as bilateral visual acuity (VA) worse than 0.3 logMAR. We identified 8320 cases of new-onset bilateral VI (incidence rate, 6.0/1000 person-years). Increased alcohol intake was positively and dose-dependently associated with elevated incidence of VI (ptrend < 0.001). With lifetime abstinence (reference), the multivariable-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) for incident VI with alcohol intake of <10, 10 to <20, 20–39.9, and ≥40 g/day were 1.07 (0.96–1.19), 1.15 (1.03–1.30), 1.15 (1.01–1.30), and 1.23 (1.08–1.40), respectively. Frequent binge drinking (≥once/per week) was associated with elevated risk of VI (HRs, 1.22; 95% CIs: 1.13–1.32). Former drinkers, particularly men, were at a higher risk for incident VI than lifetime abstainers. Similar associations were observed on evaluating changes in alcohol consumption and other confounders as time-varying covariates. Alcohol consumption, both in moderation and excess, was associated with increased VI incidence.
Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG
Authors: Hotz Julian Frederic , Peters Lynn , Kapp-Schwörer Silke , Theis Frauke , Eberhardt Nina , Essig Andreas , Grüner Beate , Hagemann Jürgen Benjamin
Published: February 2022

Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.
Transmissible Cancer Evolution: The Under-Estimated Role of Environmental Factors in the “Perfect Storm” Theory
Authors: Tissot Sophie , Gérard Anne-Lise , Boutry Justine , Dujon Antoine M. , Russel Tracey , Siddle Hannah , Tasiemski Aurélie , Meliani Jordan , Hamede Rodrigo , Roche Benjamin , Ujvari Beata , Thomas Frédéric
Published: February 2022

Although the true prevalence of transmissible cancers is not known, these atypical malignancies are likely rare in the wild. The reasons behind this rarity are only partially understood, but the “Perfect Storm hypothesis” suggests that transmissible cancers are infrequent because a precise confluence of tumor and host traits is required for their emergence. This explanation is plausible as transmissible cancers, like all emerging pathogens, will need specific biotic and abiotic conditions to be able to not only emerge, but to spread to detectable levels. Because those conditions would be rarely met, transmissible cancers would rarely spread, and thus most of the time disappear, even though they would regularly appear. Thus, further research is needed to identify the most important factors that can facilitate or block the emergence of transmissible cancers and influence their evolution. Such investigations are particularly relevant given that human activities are increasingly encroaching into wild areas, altering ecosystems and their processes, which can influence the conditions needed for the emergence and spread of transmissible cell lines.
Design, Characterization, and Antimicrobial Evaluation of Copper Nanoparticles Utilizing Tamarixinin a Ellagitannin from Galls of Tamarix aphylla
Authors: Orabi Mohamed A. A. , Salem-Bekhit Mounir M. , Taha Ehab I. , Abdel-Sattar El-Shaymaa , Alqahtani Omaish Salman , Al-Joufi Fakhria A. , Abdel-Wahab Basel A. , Alshabi Ali Mohamed , Alyami Hamad S. , Ahmad Javed , Hatano Tsutomu
Published: February 2022

The application of plant extracts or plant-derived compounds in the green synthesis of metal nanoparticles (NPs) was researched. Determining the exact metabolite implicated in the formation of NPs would necessitate comprehensive investigations. Copper nanoparticles (CuNPs) are gaining a lot of attention because of their unique properties and effectiveness against a wide range of bacteria and fungi, as well as their potential for usage in catalytic, optical, electrical, and microelectronics applications. In the course of this study, we aimed to formulate CuNPs utilizing pure tamarixinin A (TA) ellagitannin isolated from Tamarix aphylla galls. The main particle size of the formed CuNPs was 44 ± 1.7 nm with zeta potential equal to −23.7 mV, which emphasize the stability of the CuNPs. The X-ray diffraction spectroscopy showed a typical centered cubic crystalline structure phase of copper. Scanning electron microscopy images were found to be relatively spherical and homogeneous in shape. The antimicrobial properties of TA, as well as its mediated CuNPs, have been evaluated through well diffusion assays against four bacterial, Bacillus subtilis NCTC 10400, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, and two fungal, Candida albicans and Aspergillus flavus, strains. The distinctive antimicrobial activities were noted against the fungal strains and the Gram-negative bacterial strains P. aeruginosa ATCC 27853, and E. coli ATCC 25922. In conclusion, CuNPs mediated by TA can be applied for combating a wide range of bacterial and fungal species especially C. albicans, Asp. flavus, and P. aeruginosa in a variety of fields.
N-acetylcysteine (NAC) and Its Role in Clinical Practice Management of Cystic Fibrosis (CF): A Review
Authors: Guerini Marta , Condrò Giorgia , Friuli Valeria , Maggi Lauretta , Perugini Paola
Published: February 2022

N-acetylcysteine is the acetylated form of the amino acid L-cysteine and a precursor to glutathione (GSH). It has been known for a long time as a powerful antioxidant and as an antidote for paracetamol overdose. However, other activities related to this molecule have been discovered over the years, making it a promising drug for diseases such as cystic fibrosis (CF). Its antioxidant activity plays a key role in CF airway inflammation and redox imbalance. Furthermore, this molecule appears to play an important role in the prevention and eradication of biofilms resulting from CF airway infections, in particular that of Pseudomonas aeruginosa. The aim of this review is to provide an overview of CF and the role that NAC could play in preventing and eliminating biofilms, as a modulator of inflammation and as an antioxidant, restoring the redox balance within the airways in CF patients. To do this, NAC can act alone, but it can also be used as an adjuvant molecule to known drugs (antibiotics/anti-inflammatories) to increase their activity.
Recent Advances in the Biological Activity of s-Triazine Core Compounds
Authors: Maliszewski Dawid , Drozdowska Danuta
Published: February 2022

An effective strategy for successful chemotherapy relies on creating compounds with high selectivity against cancer cells compared to normal cells and relatively low cytotoxicity. One such approach is the discovery of critical points in cancer cells, i.e., where specific enzymes that are potential therapeutic targets are generated. Triazine is a six-membered heterocyclic ring compound with three nitrogen replacing carbon-hydrogen units in the benzene ring structure. The subject of this review is the symmetrical 1,3,5-triazine, known as s-triazine. 1,3,5-triazine is one of the oldest heterocyclic compounds available. Because of its low cost and high availability, it has attracted researcher attention for novel synthesis. s-Triazine has a weak base, it has much weaker resonance energy than benzene, therefore, nucleophilic substitution is preferred to electrophilic substitution. Heterocyclic bearing a symmetrical s-triazine core represents an interesting class of compounds possessing a wide spectrum of biological properties such as anti-cancer, antiviral, fungicidal, insecticidal, bactericidal, herbicidal and antimicrobial, antimalarial agents. They also have applications as dyes, lubricants, and analytical reagents. Hence, the group of 1,3,5-triazine derivatives has developed over the years. Triazine is not only the core amongst them, but is also a factor increasing the kinetic potential of the entire derivatives. Modifying the structure and introducing new substituents makes it possible to obtain compounds with broad inhibitory activity on processes such as proliferation. In some cases, s-triazine derivatives induce cell apoptosis. In this review we will present currently investigated 1,3,5-triazine derivatives with anti-cancer activities, with particular emphasis on their inhibition of enzymes involved in the process of tumorigenesis.
Lipid Nanoparticle Delivery Systems to Enable mRNA-Based Therapeutics
Authors: Semple Sean C. , Leone Robert , Barbosa Christopher J. , Tam Ying K. , Lin Paulo J. C.
Published: February 2022

The world raced to develop vaccines to protect against the rapid spread of SARS-CoV-2 infection upon the recognition of COVID-19 as a global pandemic. A broad spectrum of candidates was evaluated, with mRNA-based vaccines emerging as leaders due to how quickly they were available for emergency use while providing a high level of efficacy. As a modular technology, the mRNA-based vaccines benefitted from decades of advancements in both mRNA and delivery technology prior to the current global pandemic. The fundamental lessons of the utility of mRNA as a therapeutic were pioneered by Dr. Katalin Kariko and her colleagues, perhaps most notably in collaboration with Drew Weissman at University of Pennsylvania, and this foundational work paved the way for the development of the first ever mRNA-based therapeutic authorized for human use, COMIRNATY®. In this Special Issue of Pharmaceutics, we will be honoring Dr. Kariko for her great contributions to the mRNA technology to treat diseases with unmet needs. In this review article, we will focus on the delivery platform, the lipid nanoparticle (LNP) carrier, which allowed the potential of mRNA therapeutics to be realized. Similar to the mRNA technology, the development of LNP systems has been ongoing for decades before culminating in the success of the first clinically approved siRNA-LNP product, ONPATTRO®, a treatment for an otherwise fatal genetic disease called transthyretin amyloidosis. Lessons learned from the siRNA-LNP experience enabled the translation into the mRNA platform with the eventual authorization and approval of the mRNA-LNP vaccines against COVID-19. This marks the beginning of mRNA-LNP as a pharmaceutical option to treat genetic diseases.
Enhanced Differentiation Capacity and Transplantation Efficacy of Insulin-Producing Cell Clusters from Human iPSCs Using Permeable Nanofibrous Microwell-Arrayed Membrane for Diabetes Treatment
Authors: Shim In Kyong , Lee Seong Jin , Lee Yu Na , Kim Dohui , Goh Hanse , Youn Jaeseung , Jang Jinah , Kim Dong Sung , Kim Song Cheol
Published: February 2022

Although pancreatic islet transplantation is a potentially curative treatment for insulin-dependent diabetes, a shortage of donor sources, low differentiation capacity, and transplantation efficacy are major hurdles to overcome before becoming a standard therapy. Stem cell-derived insulin-producing cells (IPCs) are a potential approach to overcoming these limitations. To improve the differentiation capacity of the IPCs, cell cluster formation is crucial to mimic the 3D structure of the islet. This study developed a biodegradable polycaprolactone (PCL) electrospun nanofibrous (NF) microwell-arrayed membrane permeable to soluble factors. Based on the numerical analysis and experimental diffusion test, the NF microwell could provide sufficient nutrients, unlike an impermeable PDMS (polydimethylsiloxane) microwell. The IPC clusters in the NF microwells showed higher gene expression of insulin and PDX1 and insulin secretion than the PDMS microwells. The IPC clusters in the NF microwell-arrayed membrane could be directly transplanted. Transplanted IPC clusters in the microwells survived well and expressed PDX1 and insulin. Additionally, human c-peptide was identified in the blood plasma at two months after transplantation of the membranes. The NF microwell-arrayed membrane can be a new platform promoting IPC differentiation capacity and realizing an in situ transplantation technique for diabetic patients.
Effect of GSTA1 Variants on Busulfan-Based Conditioning Regimen Prior to Allogenic Hematopoietic Stem-Cell Transplantation in Pediatric Asians
Authors: Nguyen Ai-Hoc , Biswas Mohitosh , Puangpetch Apichaya , Prommas Santirhat , Pakakasama Samart , Anurathapan Usanarat , Rachanakul Jiratha , Sukprasong Rattanaporn , Nuntharadtanaphong Nutthan , Jongjitsook Nutcha , Hongeng Suradej , Sukasem Chonlaphat
Published: February 2022

Busulfan is widely used as a chemotherapy treatment before hematopoietic stem-cell transplantation (HSCT). However, the response of busulfan is highly variable and unpredictable, whereby the pharmacogenetic interference of glutathione S-transferase (GST) has strong evidence in Caucasians and some adult Asians but not in pediatric Asian patients. This study was aimed at investigating the associations of GST genetic polymorphisms with variations in the pharmacokinetic (PK) properties of busulfan in pediatric Asian patients. This retrospective cohort study recruited 92 pediatric patients. The polymorphism of GSTA1 was genotyped by Sanger sequencing, and GSTM1 and GSTP1 were genotyped by real-time PCR. Drug concentration and PK estimation were identified using an LC-MS/MS method and a noncompartmental model. Statistical analysis was performed by R software. Out of 92 patients, 48 (53%) were males, the mean age was 8.4 ± 5.12 years old, and the average weight was 26.52 ± 14.75 kg. The allele frequencies of GSTA1*B and of GSTM1 and GSTP1* deletions were 16.9%, 68.5%, and 21.2%, respectively. Patients with GSTA1*B had a statistically significant impact on the PK of busulfan, whereas those with GSTM1 and GSTP1 did not (p > 0.05). The carriers of GSTA1*B showed a significant difference compared to noncarriers in terms of t1/2 (for first dose: 161.9 vs. 134.3 min, p = 0.0016; for second dose: 156.1 vs. 129.8, p = 0.012), CL (88.74 vs. 124.23 mL/min, p = 0.0089), Cmax (4232.6 vs. 3675.5 ng/mL, p = 0.0021), and AUC (5310.6 vs. 4177.1 µM/min, p = 0.00033). The augmentation of AUC was around 27.1% in patients carrying the GSTA1*B variant. The GSTA1 polymorphism was significantly associated with variations of the pharmacokinetic properties of busulfan treatment in pediatric Asian patients.
Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment
Authors: Páez-Franco José C. , Zermeño-Ortega Miriam R. , de la O-Contreras Carmen Myriam , Canseco-González Daniel , Parra-Unda Jesus R. , Avila-Sorrosa Alcives , Enríquez Raúl G. , Germán-Acacio Juan M. , Morales-Morales David
Published: February 2022

Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.
Photosensitive EGFR-Targeted Nanocarriers for Combined Photodynamic and Local Chemotherapy
Authors: de las Heras Elena , Sagristá M. Lluïsa , Agut Montserrat , Nonell Santi
Published: February 2022

The major limitation of any cancer therapy lies in the difficulty of precisely controlling the localization of the drug in the tumor cells. To improve this drawback, our study explores the use of actively-targeted chemo-photo-nanocarriers that recognize and bind to epidermal growth factor receptor-overexpressing cells and promote the local on-demand release of the chemotherapeutic agent doxorubicin triggered by light. Our results show that the attachment of high concentrations of doxorubicin to cetuximab-IRDye700DX-mesoporous silica nanoparticles yields efficient and selective photokilling of EGFR-expressing cells mainly through singlet oxygen-induced release of the doxorubicin from the nanocarrier and without any dark toxicity. Therefore, this novel triply functionalized nanosystem is an effective and safe nanodevice for light-triggered on-demand doxorubicin release.
Physiologically Based Pharmacokinetic (PBPK) Model of Gold Nanoparticle-Based Drug Delivery System for Stavudine Biodistribution
Authors: Zazo Hinojal , Colino Clara I. , Gutiérrez-Millán Carmen , Cordero Andres A. , Bartneck Matthias , Lanao José M.
Published: February 2022

Computational modelling has gained attention for evaluating nanoparticle-based drug delivery systems. Physiologically based pharmacokinetic (PBPK) modelling provides a mechanistic approach for evaluating drug biodistribution. The aim of this work is to develop a specific PBPK model to simulate stavudine biodistribution after the administration of a 40 nm gold nanoparticle-based drug delivery system in rats. The model parameters used have been obtained from literature, in vitro and in vivo studies, and computer optimization. Based on these, the PBPK model was built, and the compartments included were considered as permeability rate-limited tissues. In comparison with stavudine solution, a higher biodistribution of stavudine into HIV reservoirs and the modification of pharmacokinetic parameters such as the mean residence time (MRT) have been observed. These changes are particularly noteworthy in the liver, which presents a higher partition coefficient (from 0.27 to 0.55) and higher MRT (from 1.28 to 5.67 h). Simulated stavudine concentrations successfully describe these changes in the in vivo study results. The average fold error of predicted concentrations after the administration of stavudine-gold nanoparticles was within the 0.5–2-fold error in all of the tissues. Thus, this PBPK model approach may help with the pre-clinical extrapolation to other administration routes or the species of stavudine gold nanoparticles.
PEGylated Chitosan Nanoparticles Encapsulating Ascorbic Acid and Oxaliplatin Exhibit Dramatic Apoptotic Effects against Breast Cancer Cells
Authors: Fahmy Sherif Ashraf , Ramzy Asmaa , Mandour Asmaa A. , Nasr Soad , Abdelnaser Anwar , Bakowsky Udo , Azzazy Hassan Mohamed El-Said
Published: February 2022

This study aims to design a pH-responsive dual-loaded nanosystem based on PEGylated chitosan nanoparticles loaded with ascorbic acid (AA) and oxaliplatin (OX) for the effective treatment of breast cancer. In this regard, non-PEGylated and PEGylated chitosan nanoparticles (CS NPs) loaded with either ascorbic acid (AA), oxaliplatin (OX), or dual-loaded with AA-OX were fabricated using the ionotropic gelation method. The hydrodynamic diameters of the fabricated AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs were 157.20 ± 2.40, 188.10 ± 9.70, and 261.10 ± 9.19 nm, respectively. While the hydrodynamic diameters of the designed AA/PEG-CS NPs, OX/PEG-CS NPs, and AA-OX/PEG-CS NPs were 152.20 ± 2.40, 156.60 ± 4.82, and 176.00 ± 4.21 nm, respectively. The ζ-potential of the prepared nanoparticles demonstrated high positive surface charges of +22.02 ± 1.50, +22.58 ± 1.85 and +40.4 ± 2.71 mV for AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs, respectively. The ζ-potential of the PEGylated CS NPs was reduced owing to the shielding of the positive charges by the PEG chains. Additionally, all the prepared nanoparticles exhibited high entrapment efficiencies (EE%) and spherical-shaped morphology. The chemical features of the prepared nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy. Release studies showed the capability of the prepared non-PEGylated and PEGylated chitosan NPs to release their cargo in the acidic environment of cancer tissue (pH 5.5). Furthermore, the AA/CS NPs, AA/PEG-CS NPs, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs and AA-OX/PEG-CS NPs exhibited remarkable cytotoxic activities against breast adenocarcinoma (MCF-7) cells with IC50 values of 44.87 ± 11.49, 23.3 ± 3.73, 23.88 ± 6.29, 17.98 ± 3.99, 18.69 ± 2.22, and 7.5 ± 0.69 µg/mL, respectively; as compared to free AA and OX (IC50 of 150.80 ± 26.50 and 147.70 ± 63.91 µg/mL, respectively). Additionally, treatment of MCF-7 cells with IC50 concentrations of AA, AA/CS NPs, AA/PEG-CS NPs, OX, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs or AA-OX/PEG-CS NPs increased the percentages of early apoptotic cells to 5.28%, 9.53%, 11.20%, 5.27%, 13.80%, 8.43%, 2.32%, and 10.10%, respectively, and increased the percentages of late apoptotic cells to 0.98%, 0.37%, 2.41%, 2.06%, 0.97%, 9.66%, 56%, and 81.50%, respectively. These results clearly indicate that PEGylation enhances the apoptotic effect of AA and OX alone, in addition to potentiating the apoptotic effect of AA and OX when combined on MCF-7 cells. In conclusion, PEGylated chitosan nanoparticles encapsulating AA, OX, or AA and OX represent an effective formula for induction of apoptosis in MCF-7 cells.