bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of Cotton Fabric with Molecularly Imprinted Polymer-Coated Carbon Dots as a Sensor for 17 α-methyltestosterone
Authors: Lim Monyratanak , Thanasupsin Sudtida Pliankarom , Thongkon Nisakorn
Published: October 2022

Molecularly imprinted polymers@ethylenediamine-modified carbon dots grafted on cotton fabrics (MIPs@EDA-CDs/CF) and smartphone-based fluorescence image analysis were proposed and used for the first time for the detection of 17 α-methyltestosterone (MT). The EDA-CDs were synthesized and grafted on cotton fabric before coating with the MIPs. The MIPs were synthesized using the MT as a template molecule, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, and azobisisobutyronitrile (AIBN) as an initiator. The MIPs@EDA-CDs/CF were characterized using FTIR, SEM-EDS, and RGB fluorescence imaging. The fluorescence images were also taken using a smartphone and the ImageJ program was used for RGB measurement. The Δ red intensity was linearly proportional to MT concentration in the range of 100 to 1000 μg/L (R2 = 0.999) with a detection limit of 44.4 μg/L and quantification limit of 134 μg/L. The MIPs@EDA-CDs/CF could be stored at 4 °C for a few weeks and could be reused twice. The proposed method could apply for the specific determination of MT in water and sediment samples along with satisfactory recoveries of 96–104% and an acceptable relative standard deviation of 1–6% at the ppb level.
Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities
Authors: Zhu Qin-Feng , Xu Guo-Bo , Liao Shang-Gao , Yan Xue-Long
Published: October 2022

The roots of Euphorbia fischeriana have been used as a traditional Chinese medicine for the treatment of tuberculosis and ringworm. In the current study, diterpenoids from the ethyl acetate extract of the roots E. fischeriana and their cytotoxic effects against five cancer lines were investigated. Two new ent-abietane diterpenoids, euphonoids H and I (1–2), as well as their two analogues (3–4) were first isolated from this source. The structures of the two new compounds were elucidated on the basis of spectroscopic data and quantum chemical calculation. Their absolute configurations were assigned via ECD spectrum calculation. The isolated compounds were evaluated for their antiproliferative activities against five cancer cell lines. Compounds 1 and 2 exhibited significant inhibitory effects against human prostate cancers C4-2B and C4-2B/ENZR cell lines with IC50 values ranging from 4.16 ± 0.42 to 5.74 ± 0.45 μM.
In Vivo Evaluation of Anti-Nociceptive Effects of Silver Nanoparticles
Authors: Morsi Shereen , Pittala Valeria , Alqudah Mohammad , Haider Mohamed , Greish Khaled
Published: October 2022

Silver nanoparticles (AgNPs) are widely used commercially due to their antimicrobial effects. Little is known about the effect of AgNPs on neural transmission and pain response. The aim of this study was to assess the anti-nociceptive activity of AgNPs. AgNPs were prepared at 16 ug/mL, white albino rats were injected with various doses of AgNPs, and challenged using a hot-plate test and paw withdrawal latency (PWL) was measured. The chronic constriction injury (CCI) model was utilized to evaluate the pedal withdrawal reflex and tail withdrawal reflex. An electrophysiological study was conducted utilizing colon longitudinal muscle strips. AgNPs increased the latency of PWL in a dose-dependent matter over the duration of 6 h. The paw withdrawal threshold in animals with CCI significantly increased after AgNPs administration. In isolated colon longitudinal muscle strips, AgNPs significantly reduced the colonic migrating motor complexes (MMCs) and contraction. This action was completely reversed after removing the AgNPs and adding acetylcholine to the preparation. In this study, AgNPs showed significant anti-nociception properties. To our knowledge, this is the first report to describe this pharmacological action of AgNPs.
Analysis of In Vivo Existence Forms of Nardosinone in Mice by UHPLC-Q-TOF-MS Technique
Authors: Zhang Jing , Lv Yang , Zhang Jing , Bai Yu-Sha , Li Meng-Yuan , Wang Shun-Qi , Wang Li-Li , Liu Guang-Xue , Xu Feng , Shang Ming-Ying , Cai Shao-Qing
Published: October 2022

Nardosinone, a sesquiterpene peroxide, is one of the main active constituents of the ethnomedicine Nardostachyos Radix et Rhizoma, and it has many bioactivities, such as antiarrhythmia and cardioprotection. To elucidate its in vivo existence forms, its metabolism is first studied using mice. All urine and feces are collected during the six days of oral dosing of nardosinone, and blood is collected at one hour after the last dose. Besides, to validate some metabolites, a fast experiment is performed, in which nardosinone was orally administered and the subsequent one-hour urine is collected and immediately analyzed by UHPLC-Q-TOF-MS. In total, 76 new metabolites are identified in this study, including 39, 51, and 12 metabolites in urine, plasma, and feces, respectively. Nardosinone can be converted into nardosinone acid or its isomers. The metabolic reactions of nardosinone included hydroxylation, hydrogenation, dehydration, glucuronidation, sulfation, demethylation, and carboxylation. There are 56 and 20 metabolites with the structural skeleton of nardosinone and nardosinone acid, respectively. In total, 77 in vivo existence forms of nardosinone are found in mice. Nardosinone is mainly excreted in urine and is not detected in the feces. These findings will lay the foundation for further research of the in vivo effective forms of nardosinone and Nardostachyos Radix et Rhizoma.
Thermal Activation of Coal Gangue with Low Al/Si Ratio as Supplementary Cementitious Materials
Authors: Yuan Xianli , Wu Hong , Wang Ping , Xu Fen , Ding Shuang
Published: October 2022

To effectively utilize coal gangue (CG) with low Al/Si ratio, the thermal activation method was used. The activated CG, as supplementary cementitious materials (SCMs), was added into ordinary Portland cement (OPC) to study its physical properties. The XRD results show that CG undergoes a phase transition from kaolinite to metakaolinite during activation. The NMR tests reveal that the low polymerization state Q3 is continuously broadened, and the Al coordination gradually changes from Al VI to Al V and Al IV. The CG particles are scale-like and glassy with a loose structure. By mixing the activated CG (under 800 °C) with cement (mass ratio = 3:7), the water demand of normal consistency increases by 7.2% and the initial and final setting times extend by 67 min and 81 min, respectively. The rough surface and loose structure of activated CG are the main factors contributing to the higher water demand of normal consistency. The micro-aggregate effect of the activated CG reduces the contact rate between the cement particles and water, and the interparticles, thus slowing down the process of hydration reaction, and leading to longer setting times.
Anthocyanins Formulated with Carboxymethyl Starch for Gastric and Intestinal Delivery
Authors: De Sousa Sabino Luiz Bruno , Copes Francesco , Saulais Solène , De Brito Edy Sousa , Da Silva Júnior Ivanildo José , Le Tien Canh , Mateescu Mircea Alexandru , Mantovani Diego
Published: October 2022

Anthocyanins obtained from jambolan have been used as active agents in different carboxymethyl starch-based tablet formulations and their release profiles evaluated in simulated gastric fluids (SGF) and simulated intestinal (SIF) fluids. Structural analysis highlighted a strong interaction between anthocyanins and carboxymethyl starch, evidenced by scanning electron microscopy and infrared analysis. Tablet dissolution behavior varied according to the pH of the media, being controlled by the swelling and/or erosion of the polymeric matrix. Various formulations for immediate, fast, and sustained release of anthocyanins for 30 min, 2 h and 12 h of dissolution have been developed. It was found that monolithic carboxymethyl starch tablets loaded with powdered jambolan extract efficiently afforded the complete delivery (100% of anthocyanins) to different sites of the simulated gastrointestinal tract and ensured the stability of these pigments, which maintained their antioxidant activity.
Immunosuppressive Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii Hook. f.
Authors: Wang Yadan , Yan Jiangong , Zhang Zhongmou , Chen Minghui , Wu Xianfu , Ma Shuangcheng
Published: October 2022

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A–J (1–10), were isolated from the roots of T. wilfordii, along with ten known analogues (11–20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9–16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 μg/mL, 8.75 μM, 0.74 μM, and 15.66 μM, respectively, and no influence on the cell viability at a concentration of 100 μg/mL (TA) or 100 μM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.
Proteomic Analysis of the Effect of Salmonella Challenge on Broiler Chicken
Authors: Adetunji Adedeji , Casey Theresa , Franco Jackeline , Shah Devendra , Fasina Yewande
Published: October 2022

Salmonella enteritidis is a foodborne pathogen that causes high morbidity in poultry. Proteomic analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to study the effects of Salmonella infection on spleen proteome in broiler chickens. Day-old broilers were assigned to control (CON; n = 60) or Salmonella challenge (CON−SE; n = 60), and gavaged with Tryptic soy agar broth or SE. A subset of chicks was euthanized on D3 and D7 (n = 4/group/day) and the spleen was removed, and rapidly frozen, subsequently proteome was measured using label-free LC-MS/MS. Protein spectra were mapped to Gallus gallus Uniprot database. Differentially abundant proteins (DAP; FDR < 0.05) between days and treatments were identified using ANOVA. Cecal content of Salmonella in CON−SE was 3.37 log10 CFU/g and CON were negative. Across the 16 samples, 2625 proteins were identified. Proteins that decreased in abundance between days mediated cell cycle progression, while those that increased in abundance function in cytoskeleton and mRNA processing. SE infection caused an increase in proteins that mediated redox homeostasis, lysosomal activities, and energy production, while proteins decreased in abundance-mediated developmental progression. Proteomic signatures of spleen suggest SE infection was metabolically costly, and energy was diverted from normal developmental processes to potentiate disease resistance mechanisms.
Lab-in-Syringe, a Useful Technique for the Analysis and Detection of Pollutants of Emerging Concern in Environmental and Food Samples
Authors: Cerdà Víctor , Ferreira Sergio L. C. , Phansi Piyawan
Published: October 2022

Lab-in-syringe is a new approach for the integration of various analytical extraction steps inside a syringe. Fully automated dispersive liquid–liquid microextraction is carried out in-syringe using a very simple instrumental setup. Dispersion is achieved by aspiration of the organic phase and then the watery phase into the syringe as rapidly as possible. After aggregation of the solvent droplets, the organic phase is pushed towards the detector allowing a highly sensitive spectrophotometric or fluorimetric detection. This technique is very useful not only for the preconcentration of analyte, but also for the elimination of their interferences. In this work, its application is described using solvents that are lighter and denser than water. The magnetically assisted variant and its coupling to different instruments has been also described with the aim of increasing the resolution of complex samples, especially useful for the determination of emerging contaminants.
Prodigiosin from Serratia Marcescens in Cockroach Inhibits the Proliferation of Hepatocellular Carcinoma Cells through Endoplasmic Reticulum Stress-Induced Apoptosis
Authors: Wang Jie , Liu Hancong , Zhu Liuchong , Wang Jingyi , Luo Xiongming , Liu Wenbin , Ma Yan
Published: October 2022

Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor, and the targeted therapy for HCC is very limited. Our previous study demonstrated that prodigiosin(PG), a secondary metabolite from Serratia marcescens found in the intestinal flora of cockroaches, inhibits the proliferation of HCC and increases the expression of CHOP, a marker protein for endoplasmic reticulum stress (ERS)-mediated apoptosis, in a dose-dependent manner. However, the mechanisms underlying the activity of PG in vivo and in vitro are unclear. This study explored the molecular mechanisms of PG-induced ERS against liver cancer in vitro and in vivo. The apoptosis of hepatocellular carcinoma cells induced by PG through endoplasmic reticulum stress was observed by flow cytometry, colony formation assay, cell viability assay, immunoblot analysis, and TUNEL assay. The localization of PG in cells was observed using laser confocal fluorescence microscopy. Flow cytometry was used to detect the intracellular Ca2+ concentration after PG treatment. We found that PG could promote apoptosis and inhibit the proliferation of HCC. It was localized in the endoplasmic reticulum of HepG2 cells, where it induces the release of Ca2+. PG also upregulated the expression of key unfolded response proteins, including PERK, IRE1α, Bip, and CHOP, and related apoptotic proteins, including caspase3, caspase9, and Bax, but down-regulated the expression of anti-apoptotic protein Bcl-2 in liver cancer. Alleviating ERS reversed the above phenomenon. PG had no obvious negative effects on the functioning of the liver, kidney, and other main organs in nude mice, but the growth of liver cancer cells was inhibited by inducing ERS in vivo. The findings of this study showed that PG promotes apoptosis of HCC by inducing ERS.
Anticancer, Cardio-Protective and Anti-Inflammatory Potential of Natural-Sources-Derived Phenolic Acids
Authors: Afnan  , Saleem Ammara , Akhtar Muhammad Furqan , Sharif Ali , Akhtar Bushra , Siddique Rida , Ashraf Ghulam Md , Alghamdi Badrah S. , Alharthy Saif A.
Published: October 2022

Phenolic acids (PAs) are one of the utmost prevalent classes of plant-derived bioactive chemicals. They have a specific taste and odor, and are found in numerous medicinal and food plants, such as Cynomorium coccineum L., Prunus domestica (L.), and Vitis vinifera L. Their biosynthesis, physical and chemical characteristics and structure–activity relationship are well understood. These phytochemicals and their derivatives exert several bioactivities including but not limited to anticancer, cardioprotective, anti-inflammatory, immune-regulatory and anti-obesity properties. They are strong antioxidants because of hydroxyl groups which play pivotal role in their anticancer, anti-inflammatory and cardioprotective potential. They may play significant role in improving human health owing to anticarcinogenic, anti-arthritis, antihypertensive, anti-stroke, and anti-atherosclerosis activities, as several PAs have demonstrated biological activities against these disease during in vitro and in vivo studies. These PAs exhibited anticancer action by promoting apoptosis, targeting angiogenesis, and reducing abnormal cell growth, while anti-inflammatory activity was attributed to reducing proinflammatory cytokines. Pas exhibited anti-atherosclerotic activity via inhibition of platelets. Moreover, they also reduced cardiovascular complications such as myocardial infarction and stroke by activating Paraoxonase 1. The present review focuses on the plant sources, structure activity relationship, anticancer, anti-inflammatory and cardioprotective actions of PAs that is attributed to modulation of oxidative stress and signal transduction pathways, along with highlighting their mechanism of actions in disease conditions. Further, preclinical and clinical studies must be carried out to evaluate the mechanism of action and drug targets of PAs to understand their therapeutic actions and disease therapy in humans, respectively.
Portable Colorimetric Hydrogel Test Kits and On-Mobile Digital Image Colorimetry for On-Site Determination of Nutrients in Water
Authors: Wongniramaikul Worawit , Kleangklao Bussakorn , Boonkanon Chanita , Taweekarn Tarawee , Phatthanawiwat Kharittha , Sriprom Wilasinee , Limsakul Wadcharawadee , Towanlong Wanchitra , Tipmanee Danai , Choodum Aree
Published: October 2022

Portable colorimetric hydrogel test kits are newly developed for the on-site detection of nitrite, nitrate, and phosphate in water. Griess-doped hydrogel was prepared at the bottom of a 1.5 mL plastic tube for nitrite detection, a nitrate reduction film based on zinc powder was placed on the inner lid of a second 1.5 mL plastic tube for use in conjunction with the Griess-doped hydrogel for nitrate detection, and a molybdenum blue-based reagent was entrapped within a poly(vinyl alcohol) hydrogel matrix placed at the bottom of a third 1.5 mL plastic tube to detect phosphate. These test kits are usable with on-mobile digital image colorimetry (DIC) for the on-site determination of nutrients with good analytical performance. The detection limits were 0.02, 0.04, and 0.14 mg L−1 for nitrite, nitrate, and phosphate, respectively, with good accuracy (<4.8% relative error) and precision (<1.85% relative standard deviation). These test kits and on-mobile DIC were used for the on-site determination of nutrients in the Pak Bang and Bang Yai canals, the main canals in Phuket, Thailand. The concentrations of nitrite, nitrate, and phosphate were undetectable to 0.60 mg L−1, undetectable to 2.98 mg L−1, and undetectable to 0.52 mg L−1, respectively.
The Effects of Nettle Extract Consumption on Liver PPARs, SIRT1, ACOX1 and Blood Lipid Levels in Male and Female C57Bl6 Mice
Authors: Domjanić Drozdek Sandra , Odeh Dyana , Đikić Domagoj , Gračan Romana , Oršolić Nada , Dragović-Uzelac Verica , Feher-Turković Lana , Dragičević Petar , Landeka Jurčević Irena
Published: October 2022

The aim of this study was to evaluate how nettle (Urtica dioica L.) water extract consumption would interact with regulators of peroxysomal lipid oxidation, histone deacetylase, and markers of oxidative stress in the liver and blood lipid levels in male and female C57Bl6 mice. Metabolically unchallenged (healthy) mice (n = 5 per sex) were treated with a nettle extract in a dose of 40 mg of total polyphenols in the extract per kg mice body weight. The nettle extract was applied daily along with normal diet for 15 days. The serum triglycerides, cholesterol, HDL, LDL, and liver PPAR-α, PPAR-γ, PGC-1-α, ACOX1, SIRT1, MDA, SOD, CAT, and GSH were compared between exposed and unexposed (control) animals. In males, the PPAR-α, PGC1-α, and ACOX1 levels together with systemic HDL cholesterol were significantly (p ≤ 0.05) increased while the LDL cholesterol decreased (p ≤ 0.05). In females, no changes in PPAR-α and PGC1-α or serum lipids were noted, but the ACOX1 content in the liver was significantly (p ≤ 0.05) increased. The SIRT1 activity increased (p ≤ 0.05) only in females. In both sexes, the PPAR-γ levels were not significantly (p ≤ 0.05) affected in either sex. The results indicate that nettle plant extract has the potential to modulate selected transcriptional factors and histone deacetylase in vivo, with certain sex differences, which should be studied further in similar models.
Parenteral Nutrition Overview
Authors: Berlana David
Published: October 2022

Parenteral nutrition (PN) is a life-saving intervention for patients where oral or enteral nutrition (EN) cannot be achieved or is not acceptable. The essential components of PN are carbohydrates, lipids, amino acids, vitamins, trace elements, electrolytes and water. PN should be provided via a central line because of its hypertonicity. However, peripheral PN (with lower nutrient content and larger volume) can be administered via an appropriate non-central line. There are alternatives for the compounding process also, including hospital pharmacy compounded bags and commercial multichamber bags. PN is a costly therapy and has been associated with complications. Metabolic complications related to macro and micronutrient disturbances, such as hyperglycemia, hypertriglyceridemia, and electrolyte imbalance, may occur at any time during PN therapy, as well as infectious complications, mostly related to venous access. Long-term complications, such as hepatobiliary and bone disease are associated with longer PN therapy and home-PN. To prevent and mitigate potential complications, the optimal monitoring and early management of imbalances is required. PN should be prescribed for malnourished patients or high-risk patients with malnutrition where the feasibility of full EN is in question. Several factors should be considered when providing PN, including timing of initiation, clinical status, and risk of complications.
The Association between Iron and Folic Acid Supplementation and Malaria Prophylaxis and Linear Growth among Children and Neonatal Mortality in Sub-Saharan Africa—A Pooled Analysis
Authors: Godha Deepali , Tharaney Manisha , Nanama Simeon , Sanghvi Tina , Laillou Arnaud , Diop Fanta Touré , Cisse Aita Sarr
Published: October 2022

The majority of research on linear growth among children is confined to South Asia and focuses on iron and folic acid (IFA) supplementation during pregnancy, without considering malaria prophylaxis. Similarly, there is limited evidence on the association of antenatal IFA supplementation and malaria prophylaxis with neonatal mortality in sub-Saharan Africa (SSA). This study aims to address these gaps. A pooled analysis of demographic and health survey (DHS) data from 19 countries in SSA was conducted to study the association between IFA supplementation and malaria prophylaxis and linear growth and neonatal mortality. Multivariate logistic and linear regression models were used. Malaria prophylaxis was significantly associated with stunting, height-for-age Z scores (HAZ scores), and neonatal mortality, but IFA supplementation was not associated with these outcomes. When women’s height and body mass index (BMI) were introduced in the model, a significant association between combined malaria prophylaxis and IFA supplementation was found with HAZ scores only. For severe stunting, no significant association was found with either in the two models. In conclusion, this study underscores the importance of antenatal malaria prophylaxis as a potential intervention for nutrition outcomes (linear growth) and neonatal mortality, as well as the importance of coordinating efforts between malaria and the health and nutrition sectors to improve these outcomes in the countries of SSA.
Effect of an (–)-Epicatechin Intake on Cardiometabolic Parameters—A Systematic Review of Randomized Controlled Trials
Authors: Dicks Lisa , Haddad Zeina , Deisling Stefanie , Ellinger Sabine
Published: October 2022

Growing evidence exists that consumption of cocoa-rich food improves the parameters of cardiometabolic health. These effects are ascribed to cocoa flavanols, particularly to (–)-epicatechin (EC), a natural ingredient of cocoa. Hence, to evaluate if EC may explain the effects of cocoa, this systematic review aimed to provide an overview on randomized controlled trials (RCTs) investigating the impact of an EC intake on cardiometabolic biomarkers. For this, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement was considered and the risk of bias (RoB) was assessed by using the Cochrane RoB 2 tool. In total, 11 studies were included examining parameters on vascular function, glucose/lipid metabolism, oxidative stress, inflammation, appetite sensations, and body weight before and after EC treatment. Except for a dose-dependent acute increase in flow-mediated dilatation (FMD) and in the peripheral arterial tonometry (PAT) index in healthy young adults, effects by EC treatment were not observed. For most trials, some concerns exist for overall RoB. Thus, EC intake may improve endothelial function in healthy young adults. For further parameters (mostly secondary outcomes), it remains unclear if EC has no effect or if this was not detectable. Unbiased RCTs on the impact of an EC intake are needed, which should also investigate the additive or synergistic effects of EC with other cocoa ingredients.
Slow Drinking of Beer Attenuates Subjective Sedative Feeling in Healthy Volunteers: A Randomized Crossover Pilot Study
Authors: Oshima Shunji , Shiiya Sachie , Kato Yasuhito
Published: October 2022

The change in physiological parameters and subjective feelings according to the speed of drinking alcohol has not been reported to date. The aim of this randomized crossover pilot study was to investigate the objective and subjective effects of different speeds of alcohol ingestion in healthy volunteers. Accordingly, 11 male and 7 female healthy Japanese adults were asked to consume 480 mL of beer at three different drinking speeds (80, 40, and 20 mL/5 min). According to the objective measurement, the transient increase in blood alcohol and serum uric acid concentrations was most inhibited at a drinking speed of 20 mL/5 min. Acetate, lactate, pyruvate, and lactate/pyruvate ratios did not differ between the three drinking speeds. Stimulant feelings measured by the subjective scores of the Brief Biphasic Alcohol Effects Scale did not differ between the three speeds. However, the sedative feeling score obtained at a drinking speed of 20 mL/5 min (the slowest speed of alcohol consumption) was significantly weakened in comparison with those obtained at drinking speeds of 40 and 80 mL/5 min. Therefore, a slower consumption of alcohol mitigated the subjective sedative feeling. The effects of slower alcohol consumption may be caused by the slower slope of the increasing trend of blood alcohol concentration.
Dietary Quality and Relationships with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) among United States Adults, Results from NHANES 2017–2018
Authors: Tian Ting , Zhang Jingxian , Xie Wei , Ni Yunlong , Fang Xinyu , Liu Mao , Peng Xianzhen , Wang Jie , Dai Yue , Zhou Yonglin
Published: October 2022

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new definition for the evidence of hepatic steatosis and metabolic dysfunctions. The specific role of the dietary factors in the development and progress of the disease are not well illuminated. Thus, we conducted this study on the associations between dietary quality assessed by five dietary quality indexes (Dietary Inflammatory Index, DII; Mediterranean diet, MED; Dietary Approach to Stop Hypertension, DASH; Alternate Healthy Eating Index diet, AHEI; Healthy Eating Indices, HEI) and MAFLD phenotypes. This study was extracted from the latest NHANES 2017–2018 wave. Demographic information, health status, lifestyles, and dietary habits were reported in the questionnaire. Multivariate logistic regression and multivariate ordinal logistic regression methods were applied to explore the associations between dietary quality indexes and MAFLD or MAFLD with liver fibrosis. The weighted prevalence of Non-MAFLD, MAFLD without fibrosis, and MAFLD with fibrosis were 47.05%, 36.67%, and 16.28%, respectively, at the cutoff value of a median Controlled Attenuation Parameter (CAP) 248 dB/m and a median Liver Stiffness Measurement (LSM) 6.3 kPa. When the diagnostic cutoff values of CAP changed to 285 dB/m, the weighted prevalence of Non-MAFLD, MAFLD without liver fibrosis, and MAFLD with fibrosis turned to 64.62%, 22.08%, and 13.30%, respectively. All five dietary quality indexes, including DII, HEI-2015, AHEI, DASH, and MED, were all significantly associated with MAFLD phenotypes. DII was positively associated with MAFLD phenotypes, while other four dietary quality indexes, including HEI-2015, AHEI, DASH, and MED, were significantly associated with lower risk of MAFLD phenotypes. MAFLD is becoming a threatening public health concern among adult Americans and dietary quality is markedly associated with MAFLD phenotypes.
The Fitter I Am, the Larger I Feel—The Vicious Circle of Physical Exercise in Anorexia Nervosa
Authors: Di Lodovico Laura , Hanachi Mouna , Duriez Philibert , Gorwood Philip
Published: October 2022

Introduction: Body image distortion is a core symptom of anorexia nervosa (AN), embodying dissatisfaction and overvaluation of body appearance and weight. Body image distortion is an important factor in the maintenance of weight loss behaviours such as compulsive physical exercise. Conversely, physical exercise seems to have an aggravating effect on body image in patients with AN, but the evidence is still poor. The aim of this study was to examine the relationship between body image distortion and physical exercise in AN in order to understand whether physical exercise may play a specific role in body image distortion beyond psychopathological severity. Methods: Forty patients with AN and 21 healthy controls were tested for body image distortion and different proxies of physical exercise. Univariate correlations tested the relationship between body image distortion and physical exercise in AN and control groups. Then, to experimentally assess the effect of exercise on body image distortion, participants were invited to rate their body image before and after a standardised effort test. Results: In the AN group, a correlation was found between physical activity and body image distortion (p < 0.01), which was still significant after controlling for psychopathological severity. No correlation was found in healthy controls. After a standardised effort, patients with AN had higher increases in body image distortion than healthy controls (almost 4 kg/m2 vs. 0.8 kg/m2) (p < 0.01). Discussion: Physical exercise may contribute to the distortion of body image in anorexia nervosa and explain the paradoxical augmentation of unhealthy exercise despite ongoing weight loss.
Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors
Authors: Hou Xixi , Gong Xiaoqing , Mao Longfei , Zhao Jie , Yang Jianxue
Published: October 2022

Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designed a series of compounds with urea and 1,2,3-triazole structures. Organic synthesis and IDO1 enzymatic activity experiments verified the molecular-level activities of the designed compounds, and the IC50 value of compound 3a was 0.75 μM. Molecular docking and quantum mechanical studies further explained the binding mode and reaction potential of compound 3a with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases.
Small-Molecule Fluorescent Probe for Detection of Sulfite
Authors: Li Ting , Chen Xuyang , Wang Kai , Hu Zhigang
Published: October 2022

Sulfite is widely used as an antioxidant additive and preservative in food and beverages. Abnormal levels of sulfite in the body is related to a variety of diseases. There are strict rules for sulfite intake. Therefore, to monitor the sulfite level in physiological and pathological events, there is in urgent need to develop a rapid, accurate, sensitive, and non-invasive approach, which can also be of great significance for the improvement of the corresponding clinical diagnosis. With the development of fluorescent probes, many advantages of fluorescent probes for sulfite detection, such as real time imaging, simple operation, economy, fast response, non-invasive, and so on, have been gradually highlighted. In this review, we enumerated almost all the sulfite fluorescent probes over nearly a decade and summarized their respective characteristics, in order to provide a unified platform for their standardized evaluation. Meanwhile, we tried to systematically review the research progress of sulfite small-molecule fluorescent probes. Logically, we focused on the structures, reaction mechanisms, and applications of sulfite fluorescent probes. We hope that this review will be helpful for the investigators who are interested in sulfite-associated biological procedures.
The Improved Brain-Targeted Drug Delivery of Edaravone Temperature-Sensitive Gels by Ultrasound for γ-ray Radiation-Induced Brain Injury
Authors: Li Qian , Zhang Yizhi , Hu Jinglu , Yuan Bochuan , Zhang Pengcheng , Wang Yaxin , Jin Xu , Du Lina , Jin Yiguang
Published: October 2022

Radiation-induced brain injury (RBI) is a common neurological disease caused by ionizing radiation (IR). Edaravone (EDA) is a free radical scavenger, has the potential to treat RBI. EDA loaded temperature-sensitive gels (TSGs) were prepared for subcutaneous injection to improve inconvenient administration of intravenous infusion. RBI mice model was established by irradiation of 60Co γ-ray on head. EDA TSGs could improve spontaneous behavior, learning and memory and anxiety of RBI mice by behavior tests, including the open field test, the novel object recognition test, the elevated plus maze test and the fear conditioning test. The therapeutic effects were enhanced with the assistance of ultrasound. Alleviative pathological changes, decreased the expression of Molondialdehyde (MDA) and Interleukin-6 (IL-6) in the hippocampus of brain, indicated reduced oxidative stress and inflammatory response with the treatment of EDA TSGs and ultrasound. Moreover, ultrasound was superior to the use of EDA TSGs. Safe and effective EDA TSGs were prepared for RBI, and the feasibility of brain-targeted drug delivery enhanced by ultrasound was preliminarily demonstrated in this study.
Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines
Authors: Abdelkader Hamdy , Fatease Adel Al , Fathalla Zeinab , Shoman Mai E. , Abou-Taleb Heba A. , Abourehab Mohammed A. S.
Published: October 2022

Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native β-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether β-CD), hydroxypropyl β-cyclodextrin, and hydroxyethyl β-cyclodextrin were investigated for inclusion complexes with curcumin using two preparation methods (physical mixing and solvent evaporation). The prepared complexes were studied for docking, solubility, FTIR, DSC, XRD, and dissolution rates. The best-fitting curcumin: cyclodextrins (the latter of the two CDs) were evaluated for cytotoxicity using human breast cell lines (MCF-7). Dose-dependent cytotoxicity was recorded as IC50% for curcumin, curcumin: hydroxyethyl β-cyclodextrin, and curcumin: hydroxypropyl β-cyclodextrin were 7.33, 7.28, and 19.05 µg/mL, respectively. These research findings indicate a protective role for the curcumin: hydroxypropyl β-cyclodextrin complex on the direct cell lines of MCF-7.
Immunotherapeutic Implications of Toll-like Receptors Activation in Tumor Microenvironment
Authors: Zheng Run , Ma Jian
Published: October 2022

Toll-like receptors (TLRs) play an important role between innate and adaptive immunity as one of the pattern recognition receptors (PRRs). Both immune cells and tumor cells express TLRs, and the same TLR molecule is expressed in different cells with different roles. TLR activation in the tumor microenvironment mostly has a dual role in tumor progression during chronic inflammation. Clinically, the therapeutic efficacy of most cancer immunotherapy strategies is restricted by the suppressive immune infiltrative environment within the tumor. Therefore, activation of TLRs in innate immune cells has the potential to eradicate tumors lacking T-cell infiltration. TLR agonists have served as important immunomodulators of cancer immunotherapy through immune responses and reprogramming the tumor suppressive microenvironment. Meanwhile, considering the complex interaction of TLRs with the tumor microenvironment, a combined approach of cancer immunotherapy and nanotechnology has been adopted to improve cancer immunotherapy not only by combining multiple drug combinations, but also by targeting the tumor microenvironment using nanoparticles. Many clinical trials are underway to improve antitumor activity through combination with other immunotherapies. In this review, we provide a comprehensive and detailed overview of the immunotherapeutic implications of TLRs activation in tumor microenvironment, highlighting its great potential to be an important tool for cancer immunotherapy.
Synthesis & Evaluation of Novel Mannosylated Neoglycolipids for Liposomal Delivery System Applications
Authors: Mousavifar Leila , Lewicky Jordan D. , Taponard Alexis , Bagul Rahul , Rivat Madleen , Abdullayev Shuay , Martel Alexandrine L. , Fraleigh Nya L. , Nakamura Arnaldo , Veyrier Frédéric J. , Le Hoang-Thanh , Roy René
Published: October 2022

Glycosylated NPs, including liposomes, are known to target various receptors involved in cellular carbohydrate transport, of which the mannoside binding receptors are attracting particular attention for their expression on various immune cells, cancers, and cells involved in maintaining central nervous system (CNS) integrity. As part of our interest in NP drug delivery, mannosylated glycoliposomal delivery systems formed from the self-assembly of amphiphilic neoglycolipids were developed, with a C12-alkyl mannopyranoside (ML-C12) being identified as a lead compoundcapable of entrapping, protecting, and improving the delivery of structurally diverse payloads. However, ML-C12 was not without limitations in both the synthesis of the glycolipids, and the physicochemical properties of the resulting glycoliposomes. Herein, the chemical syntheses of a novel series of mannosylated neoglycolipids are reported with the goal of further improving on the previous ML-C12 glyconanoparticles. The current work aimed to use a self-contingent strategy which overcomes previous synthetic limitations to produce neoglycolipids that have one exposed mannose residue, an aromatic scaffold, and two lipid tails with varied alkyl chains. The azido-ending carbohydrates and the carboxylic acid-ending lipid tails were ligated using a new one-pot modified Staudinger chemistry that differed advantageously to previous syntheses. The formation of stable neoglycoliposomes of controllable and ideal sizes (≈100–400 nm) was confirmed via dynamic light scattering (DLS) experiments and transmission electron microscopy (TEM). Beyond chemical advantages, the present study further aimed to establish potential improvements in the biological activity of the neoglycoliposomes. Concanavalin A (Con A) agglutination studies demonstrated efficient and stable cross-linking abilities dependent on the length of the linkers and lipid tails. The efficacy of the glycoliposomes in improving cytosolic uptake was investigated using Nile Red as probe in immune and cancer cell lines. Preliminary ex vivo safety assessments showed that the mannosylated glycoliposomes are hemocompatible, and non-immunogenic. Finally, using a model peptide therapeutic, the relative entrapment capacity and plasma stability of the optimal glycoliposome delivery system was evaluated and compared to the previous neoglycoliposomes. Overall, the new lead glycoliposome showed improved biological activity over ML-C12, in addition to having several chemical benefits including the lack of stereocenters, a longer linker allowing better sugar availability, and ease of synthesis using novel one-pot modified Staudinger chemistry.
Human Brain Organoids-on-Chip: Advances, Challenges, and Perspectives for Preclinical Applications
Authors: Castiglione Héloïse , Vigneron Pierre-Antoine , Baquerre Camille , Yates Frank , Rontard Jessica , Honegger Thibault
Published: October 2022

There is an urgent need for predictive in vitro models to improve disease modeling and drug target identification and validation, especially for neurological disorders. Cerebral organoids, as alternative methods to in vivo studies, appear now as powerful tools to decipher complex biological processes thanks to their ability to recapitulate many features of the human brain. Combining these innovative models with microfluidic technologies, referred to as brain organoids-on-chips, allows us to model the microenvironment of several neuronal cell types in 3D. Thus, this platform opens new avenues to create a relevant in vitro approach for preclinical applications in neuroscience. The transfer to the pharmaceutical industry in drug discovery stages and the adoption of this approach by the scientific community requires the proposition of innovative microphysiological systems allowing the generation of reproducible cerebral organoids of high quality in terms of structural and functional maturation, and compatibility with automation processes and high-throughput screening. In this review, we will focus on the promising advantages of cerebral organoids for disease modeling and how their combination with microfluidic systems can enhance the reproducibility and quality of these in vitro models. Then, we will finish by explaining why brain organoids-on-chips could be considered promising platforms for pharmacological applications.
Chemical and Biological Activity Profiling of Hedyosmum strigosum Todzia Essential Oil, an Aromatic Native Shrub from Southern Ecuador
Authors: Cartuche Luis , Calva James , Valarezo Eduardo , Chuchuca Nayeli , Morocho Vladimir
Published: October 2022

The present study aimed to determine the chemical composition, enantiomeric distribution and the biological profile of Hedyosmum strigosum essential oil (EO). The antioxidant properties and anticholinesterase effect were measured by spectroscopic methods and antimicrobial potency assessed against 8 bacteria and two fungi. H. strigosum is a native shrub, particularly found in Ecuador and Colombia at 2000 to 3500 m a.s.l. Chemical composition was determined by GC-MS and GC-FID. A total of 44 compounds were detected, representing more than 92% of the EO composition. The main compounds were thymol (24.35, 22.48%), α-phellandrene (12.15, 13.93%), thymol acetate (6.59, 9.39%) and linalool (8.73, 5.82%), accounting for more than 51% of the EO. The enantioselective analysis revealed the presence of 5 pure enantiomers and 3 more as a racemic mixture. The EO exerted a strong antioxidant capacity, determined by ABTS assay, with a SC50 of 25.53 µg/mL and a strong and specific antimicrobial effect against Campylobacter jejuni with a MIC value of 125 µg/mL. A moderate acetylcholinesterase inhibitory effect was also observed with an IC50 value of 137.6 µg/mL. To the best of our knowledge this is the first report of the chemical composition and biological profile of H. strigosum EO.
Pre-Carpels from the Middle Triassic of Spain
Authors: Santos Artai A. , Wang Xin
Published: October 2022

In stark contrast to the multitude of hypotheses on carpel evolution, there is little fossil evidence testing these hypotheses. The recent discovery of angiosperms from the Early Jurassic makes the search for precursors of angiosperm carpels in the Triassic more promising. Our light microscopic and SEM observations on Combina gen. nov., a cone-like organ from the Middle Triassic of Spain, indicate that its lateral unit includes an axillary anatropous ovule and a subtending bract, and the latter almost fully encloses the former. Such an observation not only favors one of the theoretical predictions but also makes some Mesozoic gymnosperms (especially conifers and Combina) comparable to some angiosperms. Combina gen. nov. appears to be an important chimeric fossil plant that may complete the evidence chain of the origin of carpels in geological history, partially narrowing the gap between angiosperms and gymnosperms.
The Other Mechanisms by Which the Rht Genes Improve the Harvest Index of Wheat
Authors: Ukozehasi Celestin , Ober Eric S. , Griffiths Howard
Published: October 2022

Uncovering the mechanism that underlies the relationship between crop height and grain yield would potentially inform the strategies for improving wheat with optimal height. The aim of the research reported here was to identify the attributes able to produce wheat yield increases in Rht genotypes without further straw-shortening. Attention was given to examination in a controlled environment the question of the mechanistic foundation that determined the relationship between wheat height and yield in lines (Rht-B1b, Rht-D1b, Rht-B1c, Rht-D1c) compared to wild types in Mercia background. In addition to height reduction, this research revealed three other mechanisms by which the Rht genes may also improve the Harvest Index (HI) of wheat: (i) low Specific Leaf Area (SLA), (ii) increased Mean Residence Time (MRT) of Nitrogen (N), and (iii) increased grain number on spike.
Indoor Vegetable Production: An Alternative Approach to Increasing Cultivation
Authors: Ampim Peter A. Y. , Obeng Eric , Olvera-Gonzalez Ernesto
Published: October 2022

As the world’s population is increasing exponentially, human diets have changed to less healthy foods resulting in detrimental health complications. Increasing vegetable intake by both rural and urban dwellers can help address this issue. However, these communities often face the challenge of limited vegetable supply and accessibility. More so, open field vegetable production cannot supply all the vegetable needs because biotic and abiotic stress factors often hinder production. Alternative approaches such as vegetable production in greenhouses, indoor farms, high tunnels, and screenhouses can help fill the gap in the supply chain. These alternative production methods provide opportunities to use less resources such as land space, pesticide, and water. They also make possible the control of production factors such as temperature, relative humidity, and carbon dioxide, as well as extension of the growing season. Some of these production systems also make the supply and distribution of nutrients to crops easier and more uniform to enhance crop growth and yield. This paper reviews these alternative vegetable production approaches which include hydroponics, aeroponics, aquaponics and soilless mixes to reveal the need for exploring them further to increase crop production. The paper also discusses facilities used, plant growth factors, current challenges including energy costs and prospects.