bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Methionine Restriction Alleviates Choline-Induced Tri-Methylamine-N-Oxide (TMAO) Elevation by Manipulating Gut Microbiota in Mice
Authors: Lu Manman , Yang Yuhui , Xu Yuncong , Wang Xiaoyue , Li Bo , Le Guowei , Xie Yanli
Published: January 2023

Dietary methionine restriction (MR) has been shown to decrease plasma trimethylamine-N-oxide (TMAO) levels in high-fat diet mice; however, the specific mechanism used is unknown. We speculated that the underlying mechanism is related with the gut microbiota, and this study aimed to confirm the hypothesis. In this study, we initially carried out an in vitro fermentation experiment and found that MR could reduce the ability of gut microbiota found in the contents of healthy mice and the feces of healthy humans to produce trimethylamine (TMA). Subsequently, mice were fed a normal diet (CON, 0.20% choline + 0.86% methionine), high-choline diet (H-CHO, 1.20% choline + 0.86% methionine), or high-choline + methionine-restricted diet (H-CHO+MR, 1.20% choline + 0.17% methionine) for 3 months. Our results revealed that MR decreased plasma TMA and TMAO levels in H-CHO-diet-fed mice without changing hepatic FMO3 gene expression and enzyme activity, significantly decreased TMA levels and expression of choline TMA-lyase (CutC) and its activator CutD, and decreased CutC activity in the intestine. Moreover, MR significantly decreased the abundance of TMA-producing bacteria, including Escherichia-Shigella (Proteobacteria phylum) and Anaerococcus (Firmicutes phylum), and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels. Furthermore, both MR and sodium butyrate supplementation significantly inhibited bacterial growth, down-regulated CutC gene expression levels in TMA-producing bacteria, including Escherichia fergusonii ATCC 35469 and Anaerococcus hydrogenalis DSM 7454 and decreased TMA production from bacterial growth under in vitro anaerobic fermentation conditions. In conclusion, dietary MR alleviates choline-induced TMAO elevation by manipulating gut microbiota in mice and may be a promising approach to reducing circulating TMAO levels and TMAO-induced atherosclerosis.
Protective Role of Chronic Exercise Training in Modulating the Impact of Hyperglycemia on Vascular Sensitivity to Ischemia-Reperfusion
Authors: Grandperrin Antoine , Bourgoin Mathilde , Gayrard Sandrine , Boulghobra Doria , Walther Guillaume , Reboul Cyril , Meyer Grégory
Published: January 2023

Hyperglycemia (HG) is associated with increased mortality and morbidity in acute ischemic events. Regardless of the tissue or organs involved, the vascular endothelium is a key target of ischemia-reperfusion (I/R) injury severity. Among endothelium-protective strategies, exercise has been widely described as useful. However, whether this strategy is able to impact the deleterious effect of HG on endothelial function during I/R has never been challenged. For this, 48 male Wistar rats were randomized into 4 groups: sedentary (Sed) or exercised (Ex, 45 min/day, 5 days/week for 5 weeks) rats, treated (hyperglycemic, HG) or not (normoglycemic, NG) with streptozotocin (40 mg/kg, 48 h before procedure). Vascular I/R (120/15 min) was performed by clamping the femoral artery. Arterial and downstream muscular perfusions were assessed using laser speckle contrast imaging. Vascular endothelial function was assessed in vivo 15 min after reperfusion. HG was responsible for impairment of reperfusion blood flow as well as endothelial function. Interestingly exercise was able to prevent those impairments in the HG group. In agreement with the previous results, HG increased reactive oxygen species production and decreased nitric oxide bioavailability whereas exercise training normalized these parameters. It, therefore, appears that exercise may be an effective prevention strategy against the exacerbation of vascular and muscular damage by hyperglycemia during I/R.
Reproducibility and Validity of a Self-Administered Food Safety Assessment Tool on Children and Adolescent’s Risk Perception, Knowledge, and Practices
Authors: Batista Sueny Andrade , Ginani Verônica Cortez , Stedefeldt Elke , Nakano Eduardo Yoshio , Botelho Raquel Braz Assunção
Published: January 2023

The present study aimed to verify the instrument’s reliability and validity for assessing children and adolescents’ risk perception, knowledge, and food safety practices in the school context. Moreover, it aimed to test the hypothesis that both application methods (paper and pencil (PAPI) and online) are valid. The instrument comprised three questionnaires and followed a strict protocol to combine online and PAPI models, resulting in five application forms. The sample consisted of 439 Brazilian students from 10 to 14 years old (y/o). The results related to reliability and validity indicated that the knowledge questionnaire presented adequate stability and discriminant validity coefficients. The self-reported practices questionnaire obtained acceptable coefficients of stability and internal consistency. Regarding risk perception data, it was observed that students attribute a low probability of Foodborne Diseases (FBD) outbreaks occurrence and low severity of possible symptoms. In addition, students demonstrated insufficient knowledge and inadequate practices on issues related to failures associated with the time and temperature of preparation, storage, and exposure of food, contamination of food, and consumption of unsafe food. In this context, the reproducibility and validity indices need to be interpreted and discussed correctly, and young people in food safety actions are a priority in facing FBD.
Variation in the Early Life and Adult Intestinal Microbiome of Intra-Uterine Growth Restricted Rat Offspring Exposed to a High Fat and Fructose Diet
Authors: Maggiotto Liesbeth V. , Ghosh Shubhamoy , Shin Bo-Chul , Ganguly Amit , Lagishetty Venu , Jacobs Jonathan P. , Devaskar Sherin U.
Published: January 2023

Intra-Uterine Growth Restriction (IUGR) is a risk factor for many adult-onset chronic diseases, such as diabetes and obesity. These diseases are associated with intestinal microbiome perturbations (dysbiosis). The establishment of an intestinal microbiome begins in utero and continues postnatally (PN). Hypercaloric diet-induced dysbiosis is a major driver of childhood obesity. We hypothesized that different postnatal diets superimposed on IUGR will alter the postnatal intestinal microbiome. We compared four experimental rat groups: (1) Ad lib fed regular chow diet pre- and postnatally (CON), (2–3) IUGR induced by maternal caloric restriction prenatally followed postnatally (PN) by either (2) the control diet (IUGR-RC) or (3) High-Fat-high-fructose (IUGR-HFhf) diet, and lastly (4) HFhf ad lib pre- and postnatally (HFhf). Fecal samples were collected from dams and male and female rat offspring at postnatal day 2, 21, and adult day 180 for 16S rRNA gene sequencing. Maternal diet induced IUGR led to dysbiosis of the intestinal microbiome at PN21. Postnatal HFhf diet significantly reduced microbial diversity and worsened dysbiosis reflected by an increased Gammaproteobacteria/Clostridia ratio. Dysbiosis arising from a mismatch between IUGR and a postnatal HFhf diet may contribute to increased risk of the IUGR offspring for subsequent detrimental health problems.
Old, Nonagenarians, and Centenarians in Cilento, Italy and the Association of Lifespan with the Level of Some Physicochemical Elements in Tap Drinking Water
Authors: Aliberti Silvana Mirella , Funk Richard H. W. , Ciaglia Elena , Gonnella Joseph , Giudice Aldo , Vecchione Carmine , Puca Annibale Alessandro , Capunzo Mario
Published: January 2023

Longevity, as a complex life-history trait, shares an ontogenetic relationship with other quantitative traits, such as epigenetic and environmental factors. Therefore, it is important to identify environmental factors that may modify the epigenome to establish healthy aging. This study explored the association between tap drinking water and longevity in Cilento, Italy, to understand whether trace elements in local drinking water may have an influence on old, nonagenarian, and centenarian people and promote their health and longevity. Data on population and water sources were collected through the National Demographic Statistics, the Cilento Municipal Archives, and the Cilento Integrated Water Service. Ordinary least squares (OLS) regression and a geographically weight regression (GWR) model were used to study the spatial relationship between the explanatory and outcome variables of longevity. The results of the study showed that the prevalence of longevity is concentrated in the central, northern and southeastern areas of the territory and that some trace elements present in tap water may contribute to local longevity in Cilento. Specifically, all Cilento municipalities had alkaline tap water, and the municipalities with the highest longevity concentrations had higher alkalinity levels than the other municipalities, soft to medium-hard water hardness, an amount of total dissolved solids equivalent to the level of excellent water, lower amounts of sodium, adequate iron concentration, and adequate dietary intake of manganese per day.
Association between Dietary Inflammatory Index and Sarcopenia: A Meta-Analysis
Authors: Diao Houze , Yan Feifei , He Qingzhen , Li Mingyuan , Zheng Qingzhao , Zhu Qing , Fang Fang , Cui Weiwei
Published: January 2023

Background: The dietary inflammatory index (DII) is thought to be related to many healthy events. However, the association between the DII and sarcopenia remains unclear. Methods: The meta-analysis was conducted to evaluate the effects of the DII on the risk of sarcopenia utilizing available studies. Up to September 2022, Cochrane, PubMed, Web of Science, Medline, and EMBASE databases were searched to evaluate the relationships between the DII and sarcopenia. A random‒effects model was used to calculate the effect size and 95% confidence intervals (CIs). Result: Eleven studies with 19,954 participants were included in our meta-analysis. The results indicated that a high DII increased the risk of sarcopenia (OR = 1.16, 95%CI [1.06, 1.27], p < 0.05). The result of the dose–response analysis showed that the risk of sarcopenia increased by 1.22 times for each 1-point increase in the DII score (OR = 1.22, 95%CI [1.12, 1.33], p < 0.05). Conclusion: The meta-analysis demonstrated that the DII is associated with sarcopenia. Considering some limitations in this study, more studies are needed to verify this relationship.
Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway
Authors: Zhang Feng , Wang Mengyao , Zha Yang , Zhou Jie , Han Jihong , Zhang Shuang
Published: January 2023

Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti−inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF−κB)/NOD−like receptor protein−3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF−κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD.
Update on Anti-Inflammatory Molecular Mechanisms Induced by Oleic Acid
Authors: Santa-María Consuelo , López-Enríquez Soledad , Montserrat-de la Paz Sergio , Geniz Isabel , Reyes-Quiroz María Edith , Moreno Manuela , Palomares Francisca , Sobrino Francisco , Alba Gonzalo
Published: January 2023

In 2010, the Mediterranean diet was recognized by UNESCO as an Intangible Cultural Heritage of Humanity. Olive oil is the most characteristic food of this diet due to its high nutraceutical value. The positive effects of olive oil have often been attributed to its minor components; however, its oleic acid (OA) content (70–80%) is responsible for its many health properties. OA is an effective biomolecule, although the mechanism by which OA mediates beneficial physiological effects is not fully understood. OA influences cell membrane fluidity, receptors, intracellular signaling pathways, and gene expression. OA may directly regulate both the synthesis and activities of antioxidant enzymes. The anti-inflammatory effect may be related to the inhibition of proinflammatory cytokines and the activation of anti-inflammatory ones. The best-characterized mechanism highlights OA as a natural activator of sirtuin 1 (SIRT1). Oleoylethanolamide (OEA), derived from OA, is an endogenous ligand of the peroxisome proliferator-activated receptor alpha (PPARα) nuclear receptor. OEA regulates dietary fat intake and energy homeostasis and has therefore been suggested to be a potential therapeutic agent for the treatment of obesity. OEA has anti-inflammatory and antioxidant effects. The beneficial effects of olive oil may be related to the actions of OEA. New evidence suggests that oleic acid may influence epigenetic mechanisms, opening a new avenue in the exploration of therapies based on these mechanisms. OA can exert beneficial anti-inflammatory effects by regulating microRNA expression. In this review, we examine the cellular reactions and intracellular processes triggered by OA in T cells, macrophages, and neutrophils in order to better understand the immune modulation exerted by OA.
Effect of Mid-Adolescent Dietary Practices on Eating Behaviors and Attitudes in Adulthood
Authors: Wu Miao , Wu Lin , Ishida Akira
Published: January 2023

This paper aimed to clarify the association of mid-adolescent dietary practices and experiences with adult eating behavior and attitudes using individual data from the “Survey of Attitudes toward Shokuiku (food and nutrition education), 2019” put forth by the Ministry of Agriculture, Forestry and Fisheries of Japan. We applied conditional mixed-process models to estimate the parameters simultaneously, and used them to predict current eating consciousness, current eating behaviors in a balanced diet, dietary behavior, and attitudes toward preventing or improving lifestyle-related diseases as dependent variables. As a result, compared to those who did not have good dietary practices and experiences in mid-adolescence, participants who had good dietary practices and experiences in the same period displayed greater interest in practicing a healthier diet. These participants frequently consumed a combination of staple foods, main dishes, and side dishes, and were more concerned about preventing or improving lifestyle-related diseases. In conclusion, mid-adolescent dietary practices and experiences had a lasting influence on adult eating behaviors and attitudes in Japanese participants.
Family Household Characteristics and Stunting: An Update Scoping Review
Authors: Yani Desy Indra , Rahayuwati Laili , Sari Citra Windani Mambang , Komariah Maria , Fauziah Sherllina Rizqi
Published: January 2023

Stunting remains a public health concern in developing countries. Factors related to stunting have been categorized using various frameworks. Family plays an important role in providing nutrients for children; however, no review specifies this aspect for identifying family characteristics related to stunting. This study aimed to identify family household characteristics related to stunting among children aged less than 5 years. A scoping review was undertaken with sources from PubMed, CINAHL, and Scopus, using the keywords “family characteristics” AND “growth”. Inclusion criteria were (1) correlational study; (2) published between 2018 and 31 July 2022; (3) families with children under the age of 5 years; and (4) independent variable any measure of stunting factors from family and household factors. Of 376 articles, only 20 met the inclusion criteria of the study. The family household characteristics included individual factors (sex age, history of diarrhea, and birthplace), family factors (family headship, primary caregiver/mother, social-cultural orientation, and family system factors), and environmental factors. Various child variables, family factors, and environmental factors (the type of home, floor type, water access, source of drinking water, and household electricity) were identified as being associated with stunting. Therefore, these factors should be evaluated to prevent and control stunting, and they should be incorporated into health programs targeting stunting.
Elliptic Flow and Its Fluctuations from Transport Models for Au+Au Collisions at sNN = 7.7 and 11.5 GeV
Authors: Luong Vinh Ba , Idrisov Dim , Parfenov Petr , Taranenko Arkadiy
Published: January 2023

The elliptic flow v2 is one of the key observables sensitive to the transport properties of the strongly interacting matter formed in relativistic heavy-ion collisions. In this work, we report on the calculations of v2 and its fluctuations of charged hadrons produced in Au+Au collisions at center-of-mass energy per nucleon pair sNN = 7.7 and 11.5 GeV from several transport models and provide a direct comparison with published results from the STAR experiment. This study motivates further experimental investigations of v2 and its fluctuations with the Multi-Purpose Detector (MPD) at the NICA Collider.
Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis
Authors: Salem Heba F. , Abd El-Maboud Marwa Mohamed , Said Amira S. A. , Salem Mohamed Nabil , Sabry Dina , Hussain Nadia , El-Ghafar Omnia A. M. Abd , Hussein Raghda R. S.
Published: January 2023

Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation’s release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.
Enteric-Coated Cologrit Tablet Exhibit Robust Anti-Inflammatory Response in Ulcerative Colitis-like In-Vitro Models by Attuning NFκB-Centric Signaling Axis
Authors: Balkrishna Acharya , Singh Rani , Gohel Vivek , Arora Sagar , Dev Rishabh , Bhattacharya Kunal , Varshney Anurag
Published: January 2023

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the patients’ colorectal area culminating in an inflamed ‘leaky gut.’ The majority of UC treatments only provide temporary respite leading to its relapse. Therefore, this study investigated the efficacy of the enteric-coated ‘Cologrit’ (EC) tablet in alleviating UC-like inflammation. Cologrit is formulated using polyherbal extracts that have anti-inflammatory qualities according to ancient Ayurveda scriptures. Phytochemical profiling revealed the presence of gallic acid, rutin, ellagic acid, and imperatorin in Cologrit formulation. Cologrit treatment decreased inflammation in LPS-induced transformed THP-1 macrophages, and TNF-α-stimulated human colorectal (HT-29) cells through the modulation of NFκB activity, IL-6 production, and NFκB, IL-1β, IL-8, and CXCL5 mRNA expression levels. Cologrit also lessened human monocytic (U937) cell adhesion to HT29 cells. Methacrylic acid-ethylacrylate copolymer-coating of the enteric Cologrit tablets (EC) supported their dissolution, and the release of phytochemicals in the small intestine pH 7.0 environment in a simulated gastrointestinal digestion model. Small intestine EC digestae effectively abridged dextran sodium sulfate (2.5% w/v)-induced cell viability loss and oxidative stress in human colon epithelial Caco-2 cells. In conclusion, the enteric-coated Cologrit tablets demonstrated good small intestine-specific phytochemical delivery capability, and decreased UC-like inflammation, and oxidative stress through the regulation of TNF-α/NFκB/IL6 signaling axis.
Current Treatment Options in Homozygous Familial Hypercholesterolemia
Authors: Kayikcioglu Meral , Tokgozoglu Lale
Published: January 2023

Homozygous familial hypercholesterolemia (HoFH) is the rare form of familial hypercholesterolemia causing extremely high low-density lipoprotein cholesterol (LDL-C) levels, leading to atherosclerotic cardiovascular disease (ASCVD) in the first decades of life, if left untreated. Early diagnosis and effective lipid lowering therapy (LLT) are crucial for the prevention of early ASCVD in patients with HoFH. On-treatment LDL-C levels are the best predictor of survival. However, due to the absent or defective LDL-receptor activity, most individuals with HoFH are resistant to conventional LLT, that leads to LDL-C clearance by upregulating LDL-receptors. We are at the dawn of a new era of effective pharmacotherapies for HoFH patients, with new agents providing an LDL-receptor independent cholesterol reduction. In this context, the present review provides a summary of the currently available therapies and emerging therapeutic agents for the management of patients with HoFH, in light of recent evidence and guideline recommendations.
Role of Herbal Extracts of Catechu from Uncaria gambir in the Treatment of Chronic Diabetic Wounds
Authors: Ho Tsung-Jung , Tsai Pei-Hsuan , Hsieh Chia-Ho , Lin Jung-Hsing , Lin Yu-Wei , Wu Jia-Ru , Chen Hao-Ping
Published: January 2023

Catechu is a dried decoction from twigs with the leaves of Uncaria gambir. Its antioxidant, anti-inflammatory, and antimicrobial activities have been previously reported because of its high catechin and epicatechin content (>21%). It is also one of the components used in traditional Chinese herbal medicine, “Jinchuang Ointment,” which has excellent efficacy in treating chronic diabetic wounds. An in vivo zebrafish embryo platform and an in vitro cell-based tube formation assay were used to measure the angiogenic activity of catechu extracts. Interestingly, for the first time, catechu extracts stimulated angiogenic activity on both platforms. The expression of the IL-8 gene was induced in HMEC1 cells after treatment with catechu extracts for 1 h only. In contrast, the upregulation of FGFR2, FGFR3, NF-κB, STAT3, and vimentin persisted for 24 h. A summary of the possible mechanisms underlying the angiogenic activity of catechu extracts in HMEC1 cells is shown. Unexpectedly, catechu extracts inhibited the migration of HaCaT cells. These results can account for the intense blood flow flux in porcine excisional wound sites in our previous studies, which provides insights into the therapeutic activity of catechu extract in chronic diabetic wounds.
Psilocybin for Depression: From Credibility to Feasibility, What’s Missing?
Authors: Munafò Antonio , Arillotta Davide , Mannaioni Guido , Schifano Fabrizio , Bernardini Renato , Cantarella Giuseppina
Published: January 2023

Psilocybin has been suggested as a promising transdiagnostic treatment strategy for a wide range of psychiatric disorders. Recent findings showed that psychedelic-assisted/”psycholitic” psychotherapy should provide significant and sustained alleviation of depressive symptoms. However, to date, there have been several study limitations (e.g., small sample sizes, blinding, limited follow-up, highly screened treatment populations) and some health/political issues, including practitioners’ experience, lack of standardized protocols, psychedelics’ legal status, ethical concerns, and potential psychological/psychopathological/medical untoward effects. The focus here is on a range of clinical and methodological issues, also aiming at outlining some possible suggestions. We are confident that newer evidence, more precise protocols, and eventual reclassification policies may allow a better understanding of the real potential of psilocybin as a transdiagnostic therapeutic molecule.
Combining 3D Printing and Microfluidic Techniques: A Powerful Synergy for Nanomedicine
Authors: Sommonte Federica , Denora Nunzio , Lamprou Dimitrios A.
Published: January 2023

Nanomedicine has grown tremendously in recent years as a responsive strategy to find novel therapies for treating challenging pathological conditions. As a result, there is an urgent need to develop novel formulations capable of providing adequate therapeutic treatment while overcoming the limitations of traditional protocols. Lately, microfluidic technology (MF) and additive manufacturing (AM) have both acquired popularity, bringing numerous benefits to a wide range of life science applications. There have been numerous benefits and drawbacks of MF and AM as distinct techniques, with case studies showing how the careful optimization of operational parameters enables them to overcome existing limitations. Therefore, the focus of this review was to highlight the potential of the synergy between MF and AM, emphasizing the significant benefits that this collaboration could entail. The combination of the techniques ensures the full customization of MF-based systems while remaining cost-effective and less time-consuming compared to classical approaches. Furthermore, MF and AM enable highly sustainable procedures suitable for industrial scale-out, leading to one of the most promising innovations of the near future.
Preparation and Evaluation of 64Cu-Radiolabled Dual-Ligand Multifunctional Gold Nanoparticles for Tumor Theragnosis
Authors: Mhanna Karim , Qian Wei , Zhong Ziyun , Brooks Allen F. , Ouchi Erika , Stauff Jenelle , Arteaga Janna , Papachristou Maria , Datseris Ioannis E. , Liu Bing , Shao Xia , Scott Peter J. H.
Published: January 2023

Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto the AuNPs can be tunable between 0% and 100% coverage. By taking advantage of this property, AuNPs functionalized by two different types of active targeting ligands with predetermined ratios were fabricated. The quantitatively controllable conjugation to construct a mixed monolayer of multiple biological molecules at a certain ratio onto the surface of AuNPs was achieved and a chelator-free 64Cu-labeling method was developed. We report here the manufacture, radiosynthesis and bioevaluation of three different types of dual-ligand AuNPs functionalized with two distinct ligands selected from glucose, arginine–glycine–aspartate (RGD) peptide, and methotrexate (MTX) for tumor theragnosis. The preclinical evaluation demonstrated that tumor uptakes and retention of two components AuNP conjugates were higher than that of single-component AuNP conjugates. Notably, the glucose/MT- modified dual-ligand AuNP conjugates showed significant improvement in tumor uptake and retention. The novel nanoconjugates prepared in this study make it possible to integrate several modalities with a single AuNP for multimodality imaging and therapy, combining the power of chemo-, thermal- and radiation therapies together.
Antioxidant and Cytotoxic Activity of New Polyphenolic Derivatives of Quinazolin-4(3H)-one: Synthesis and In Vitro Activities Evaluation
Authors: Pele Raluca , Marc Gabriel , Ionuț Ioana , Nastasă Cristina , Fizeșan Ionel , Pîrnău Adrian , Vlase Laurian , Palage Mariana , Oniga Smaranda , Oniga Ovidiu
Published: January 2023

The development of hybrid molecules with significant human therapeutic properties is one of the main approaches of pharmaceutical research. One of the most important pharmacophores is the quinazolin-4(3H)-one heterocycle moiety, due to its wide range of biological activities. By its derivatization with polyphenolic compounds, in our previous research, it proved to possess a good antiradical activity of ortho-diphenolic derivatives of quinazolin-4(3H)-one. In this study, we developed two new series of compounds, with an additional phenolic group or with a methyl group on the thioacetohydrazone fragment. The methods used to evaluate the activity of the compounds were radical scavenging, reduction of oxidizing reagents and transition metals’ ions chelation assays. Quantum descriptors were also calculated in order to evaluate the influence of substituents and their position on the activity of the compounds. The cytotoxic activity was evaluated using normal human foreskin fibroblast cells (BJ) and two cancerous cell lines, lung adenocarcinoma cells (A549) and prostate carcinoma cells (LNCaP). The results obtained for the pyrogallol derivatives showed a high antioxidant activity compared to ascorbic acid and Trolox. All the synthesized compounds displayed a higher cytotoxicity against the cancerous cell types and a high cytocompatibility with the normal cells. The antioxidant activity was deeply influenced by the addition of the third phenolic group in the synthesized molecules.
Targeting Tumor-Associated Macrophages for Imaging
Authors: Hu Jiahao , Xu Xiaoling , Du Yongzhong
Published: January 2023

As an important component of the tumor immune microenvironment (TIME), tumor-associated macrophages (TAMs) occupy a significant niche in tumor margin aggregation and respond to changes in the TIME. Thus, targeting TAMs is important for tumor monitoring, surgical guidance and efficacy evaluation. Continuously developing nanoprobes and imaging agents paves the way toward targeting TAMs for precise imaging and diagnosis. This review summarizes the commonly used nanomaterials for TAM targeting imaging probes, including metal-based nanoprobes (iron, manganese, gold, silver), fluorine-19-based nanoprobes, radiolabeled agents, near-infrared fluorescence dyes and ultrasonic nanobubbles. Additionally, the prospects and challenges of designing nanomaterials for imaging and diagnosis (targeting efficiency, pharmacokinetics, and surgery guidance) are described in this review. Notwithstanding, TAM-targeting nanoplatforms provide great potential for imaging, diagnosis and therapy with a greater possibility of clinical transformation.
Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes
Authors: Türkez Hasan , Yıldırım Özge Çağlar , Öner Sena , Kadı Abdurrahim , Mete Abdulkadir , Arslan Mehmet Enes , Şahin İrfan Oğuz , Yapça Ömer Erkan , Mardinoğlu Adil
Published: January 2023

Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B4C) nanoparticles (NPs) to enhance wound healing in human dermal fibroblast (HDFa) cell culture and characterize its antimicrobial properties against Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial strains. ALA molecules are integrated onto hBN and C4B NPs through esterification procedure, and molecular characterizations are performed by using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-vis spectroscopy. Wound healing and antimicrobial properties are investigated via the use of cell viability assays, scratch test, oxidative stress, and antimicrobial activity assays. Based on our analysis, we observe that ALA-conjugated hBN NPs have the highest wound-healing feature and antimicrobial activity compared to ALA-B4C. On the other hand, hBN, ALA-B4C, and ALA compounds showed promising regenerative and antimicrobial properties. Also, we find that ALA conjugation enhances wound healing and antimicrobial potency of hBN and B4C NPs. We conclude that the ALA-hBN conjugate is a potential candidate to stimulate regeneration process for injuries.
Biopolymer-Based Nanosystems for siRNA Drug Delivery to Solid Tumors including Breast Cancer
Authors: Subhan Md Abdus , Torchilin Vladimir P.
Published: January 2023

Nanobiopolymers such as chitosan, gelatin, hyaluronic acid, polyglutamic acid, lipids, peptides, exosomes, etc., delivery systems have prospects to help overwhelmed physiological difficulties allied with the delivery of siRNA drugs to solid tumors, including breast cancer cells. Nanobiopolymers have favorable stimuli-responsive properties and therefore can be utilized to improve siRNA delivery platforms to undruggable MDR metastatic cancer cells. These biopolymeric siRNA drugs can shield drugs from pH degradation, extracellular trafficking, and nontargeted binding sites and are consequently suitable for drug internalization in a controlled-release fashion. In this review, the utilization of numerous biopolymeric compounds such as siRNA drug delivery systems for MDR solid tumors, including breast cancers, will be discussed.
Evaluation of pH-Sensitive Polymeric Micelles Using Citraconic Amide Bonds for the Co-Delivery of Paclitaxel, Etoposide, and Rapamycin
Authors: Jo Min Jeong , Shin Hee Ji , Yoon Moon Sup , Kim Seo Yeon , Jin Chae Eun , Park Chun-Woong , Kim Jin-Seok , Shin Dae Hwan
Published: January 2023

Paclitaxel (PTX), etoposide (ETP), and rapamycin (RAPA) have different mechanisms, allowing multiple pathways to be targeted simultaneously, effectively treating various cancers. However, these drugs have a low hydrosolubility, limiting clinical applications. Therefore, we used pH-sensitive polymeric micelles to effectively control the drug release in cancer cells and to improve the water solubility of PTX, ETP, and RAPA. The synergistic effect of PTX, ETP, and RAPA was evaluated in gastric cancer, and the combination index values were evaluated. Thin-film hydration was used to prepare PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles, and various physicochemical properties of these micelles were evaluated. In vitro cytotoxicity, pH-sensitivity, drug release profiles, in vivo pharmacokinetics, and biodistribution studies of PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles were evaluated. In the pH-sensitivity evaluation, the size of the micelles increased more rapidly at a pH of 5.5 than at a pH of 7.4. The release rate of each drug increased with decreasing pH values in PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles. In vitro and in vivo studies demonstrated that PTX/ETP/RAPA-loaded mPEG-pH-PCL micelles exhibit different drug release behaviors depending on the pH of the tumor and normal tissues and increased bioavailability and circulation time in the blood than solutions. Therefore, we propose that PTX/ETP/RAPA- loaded mPEG-pH-PCL micelles are advantageous for gastric cancer treatment in drug delivery systems.
The Effect of Infrared Laser Irradiation on the Surface Morphology and Electrical Properties of Zinc Metal
Authors: Asif Muhammad , Latif Anwar , Ali Ahsan , Rafique Muhammad Shahid , Khan Shakeel Ahmad , Haseeb Abdul , Shahid Muhammad Kashif
Published: January 2023

This study details the irradiation of pure (99.995%) and immaculate metallic Zinc using Nd: YAG laser (1064 nm, 10 mJ, 9–14 ns). The influence and impact of multiple laser shots on the formation of microstructures and crystal structure orientations is assessed. Arrays of ablated craters are machined on the whole surface of the target to probe the electrical and topographical characteristics of laser-treated surfaces. Irradiated samples are examined by multiple characterizing techniques such as scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and a four-point probe for electrical conductivity measurements. SEM and AFM analysis exhibited the formation of laser-induced ripple structures with periodicity sheerly dependent on laser shots. A comparison of surface topography of the virgin and treated samples disclosed a pronounced modification in surface texture. The XRD patterns of laser shined targets indicate no momentous structural change in the crystal structure, whereas the measurements on the electrical conductivity of the irradiated surfaces exhibit an exponential descending trend with an augmentation in laser shots.
Extraction of Novel Effective Nanocomposite Photocatalyst from Corn Stalk for Water Photo Splitting under Visible Light Radiation
Authors: Barakat Nasser , Gamil Aya , Ashour Ibrahim , Khalil Khalil
Published: January 2023

Novel (Ca, Mg)CO3&SiO2 NPs-decorated multilayer graphene sheets could be successfully prepared from corn stalk pith using a simple alkaline hydrothermal treatment process followed by calcination in an inert atmosphere. The produced nanocomposite was characterized by SEM, EDX, TEM, FTIR, and XRD analytical techniques, which confirm the formation of multilayer graphene sheets decorated by inorganic nanoparticles. The nanocomposite shows efficient activity as a photocatalyst for water-splitting reactions under visible light. The influence of preparation parameter variations, including the alkaline solution concentration, hydrothermal temperature, reaction time, and calcination temperature, on the hydrogen evolution rate was investigated by preparing many samples at different conditions. The experimental work indicated that treatment of the corn stalk pith hydrothermally by 1.0 M KOH solution at 170 °C for 3 h and calcinating the obtained solid at 600 °C results in the maximum hydrogen production rate. A value of 43.35 mmol H2/gcat.min has been obtained associated with the energy-to-hydrogen conversion efficiency of 9%. Overall, this study opens a new avenue for extracting valuable nanocatalysts from biomass wastes to be exploited in hot applications such as hydrogen generation from water photo-splitting under visible light radiation.
Flexible PDMS-Based SERS Substrates Replicated from Beetle Wings for Water Pollutant Detection
Authors: Lu Chen-Hsin , Cheng Ming-Ren , Chen Sheng , Syu Wei-Lin , Chien Ming-Yen , Wang Kuan-Syun , Chen Jeng-Shiung , Lee Po-Han , Liu Ting-Yu
Published: January 2023

The flexible surface-enhanced Raman scattering (SERS) sensor, which has the bionic 3D nanoarray structure of a beetle-wing substrate (BWS), was successfully prepared by replicated technology and thermal evaporation. The bionic structure was replicated with polydimethylsiloxane (PDMS) and then silver (Ag) nanoisland thin films were deposited by thermal evaporation. The deposition times and thicknesses (25–40 nm) of the Ag thin films were manipulated to find the optimal SERS detection capability. The Ag nanoisland arrays on the surface of the bionic replicated PDMS were observed by scanning electron microscope (SEM), X-ray diffraction (XRD), and contact angle, which can generate strong and reproducible three-dimensional hotspots (3D hotspots) to enhance Raman signals. The water pollutant, rhodamine 6G (R6G), was used as a model molecule for SERS detection. The results show that 35 nm Ag deposited on a PDMS-BWS SERS substrate displays the strongest SERS intensity, which is 10 times higher than that of the pristine BWS with 35 nm Ag coating, due to the excellent 3D bionic structure. Our results demonstrate that bionic 3D SERS sensors have the potential to be applied in wearable devices and sensors to detect biomolecules and environmental pollutants, such as industrial wastewater, in the future.
Experimental Study on Mechanical Properties of Basalt Fiber Concrete after Cryogenic Freeze−Thaw Cycles
Authors: Li Yang , Gu Zhicong , Zhao Ben , Zhang Jiangkun , Zou Xu
Published: January 2023

Basalt fiber (BF) has received much attention in recent years for engineering practice and scientific research related to basalt fiber reinforced concrete (BFRC) due to its advantageous mechanical properties and cost-effectiveness. By researching its performance characteristics after cryogenic freeze–thaw cycles, the advantages of BFRC’s mechanical properties can be further exploited in order to expand its application scope. The effects of the fiber volume fraction, temperature gradient, and number of freeze–thaw cycles on the compressive strength, toughness index, splitting tensile strength, flexural strength, etc., of BFRC were investigated. Additionally, the damage mechanism of BFRC after freeze–thaw cycles was analyzed via scanning electron microscopy (SEM). The results show that the compressive strength of BFRC reaches its peak value when the fraction reaches 0.1% under the conditions of freezing and thawing cycles from room temperature to −80 °C. When the fraction of BFRC is 0.1%, and the maximum reduction is 17.1%, the splitting tensile strength decreased most sharply when the fraction was 0.1%, and the decrease amplitude was 40.9%, and the flexural strength decreased most acutely when the fraction was 0.3%, and the maximum decrease was 44.62%. The addition of basalt fibers can reduce the damage to the microstructure of concrete and improve its plastic degradation characteristics to a certain extent. With a decrease in the minimum temperature of the cryogenic freeze–thaw cycle, the optimal fiber content for compressive strength increases. Nevertheless, the splitting tensile strength and flexural strength of BFRC is improved as the fiber content increases under the cryogenic freeze–thaw environment.
Jeziorny Method Should Be Avoided in Avrami Analysis of Nonisothermal Crystallization
Authors: Vyazovkin Sergey
Published: January 2023

The Jeziorny method treats nonisothermal crystallization data by replacing the variable temperature (T) values with the corresponding values of time and substituting them into the isothermal Avrami plot, ln[−ln(1 − α)] vs. lnt. For isothermal data, the slope of this plot is the Avrami exponent, n and the intercept is the rate constant, kA. This does not hold for nonisothermal data. Theoretical analysis suggests that in the case of nonisothermal data the intercept cannot be interpreted as kA, and its “correction” by dividing over the temperature change rate β is devoid of any meaning. In turn, the slope cannot be interpreted as n. It is demonstrated that the slope changes with time and its value depends not only on n but also on the temperature, temperature range, and activation energy of crystallization. Generally, the value of the slope is likely to markedly exceed the n value. The theoretical results are confirmed by analysis of simulated data. Overall, the Jeziorny method as well as other techniques that substitute nonisothermal data into the isothermal Avrami plot should be avoided as invalid and useless for any reasonable Avrami analysis. It is noted that n can be estimated from the nonlinear plot of ln[−ln(1 − α)] vs. T.
Self-Healing Performance of Asphalt Concrete with Ca-Alginate Capsules under Low Service Temperature Conditions
Authors: Wang Huoming , Liu Quantao , Wu Jie , Wan Pei , Zhao Feiyang
Published: January 2023

Calcium alginate capsules containing rejuvenators represent a promising method for asphalt concrete premaintenance, but their healing capacities under lower temperature conditions are still unknown. This paper investigated the healing performance of asphalt concrete containing calcium alginate capsules at low service temperatures. The Ca-alginate capsules were synthesized, and their morphology, compressive strength, thermal resistance, and relative oil content were evaluated. Besides, evaluations for the healing of asphalt concrete and the rejuvenator-release ratio of the capsules were determined via fracture-healing-refracture testing and Fourier-transform infrared spectrum experiments. Meanwhile, the glass transition temperature and rheological property of asphalt binder after compressive loading under different temperatures were explored via a differential scanning calorimeter and dynamic shear rheometer. The results showed that the capsules had good thermal resistance and mechanical strength. The capsules released less oil under −15, −10, and −5 °C than at 20 °C, and the healing ratios of the asphalt concrete with the capsules at −15, −10, and −5 °C were obviously lower than that at 20 °C. The released rejuvenator from the capsules could decrease the complex modulus and glass transition temperature of the asphalt binder. When compared with low service temperatures, the asphalt binder containing the capsules and serving at a high temperature has a better softening effect and low-temperature performance due to more oil being released.
Spin Trapping Analysis of Radical Intermediates on the Thermo-Oxidative Degradation of Polypropylene
Authors: Nguyen Thu Anh , Lim Hui Ming , Kinashi Kenji , Sakai Wataru , Tsutsumi Naoto , Okubayashi Satoko , Hosoda Satoru , Sato Tetsu
Published: January 2023

The purpose of this study is to investigate the thermo-oxidative degradation behavior of polypropylene (PP) by comparing three types of pristine PP granules (consisting of homopolymer, random copolymer, and block copolymer) with their corresponding oxidized analogues. These analogues were intensely oxidized under oxygen at 90 °C for 1000 h by using the electron spin resonance (ESR) spin trapping method that can detect short-lived radical intermediates during the degradation. The degrees of oxidation could be evaluated by chemiluminescence (CL) intensity, which was related to the concentration of hydroperoxide groups generated in the PP chain. In the pristine PP samples, a small amount of hydroperoxides were found to be formed unintentionally, and their homolysis produces alkoxy radicals, RO•, which then undergo β-scission to yield chain-end aldehydes or chain-end ketones. These oxidation products continue to take part in homolysis to produce their respective carbonyl and carbon radicals. On the other hand, in the oxidized PP granules, because of their much higher hydroperoxide concentration, the two-stage cage reaction and the bimolecular decomposition of hydroperoxides are energetically favorable. Carbonyl compounds are formed in both reactions, which are then homolyzed to form the carbonyl radical species, •C(O)–. PP homopolymer produced the largest amount of carbonyl radical spin adduct; thus, it was found that the homopolymer is most sensitive to oxygen attack, and the presence of ethylene units in copolymers enhances the oxidation resistance of PP copolymers.