bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxypyridinones as a Very Promising Platform for Targeted Diagnostic and Therapeutic Radiopharmaceuticals
Authors: Zhou Xu , Dong Linlin , Shen Langtao
Published: November 2021

Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals.
Prompt and Long-Lived Anti-Kasha Emission from Organic Dyes
Authors: Malpicci Daniele , Lucenti Elena , Giannini Clelia , Forni Alessandra , Botta Chiara , Cariati Elena
Published: November 2021

Anti-Kasha behavior has been the subject of intense debate in the last few years, as demonstrated by the high number of papers appearing in the literature on this topic, dealing with both mechanistic and applicative aspects of this phenomenon. Examples of anomalous emitters reported in the last 10 years are collected in the present review, which is focused on strictly anti-Kasha organic molecules displaying radiative deactivation from Sn and/or Tn, with n greater than 1.
GC-MS Analysis of Biological Nitrate and Nitrite Using Pentafluorobenzyl Bromide in Aqueous Acetone: A Dual Role of Carbonate/Bicarbonate as an Enhancer and Inhibitor of Derivatization
Authors: Tsikas Dimitrios
Published: November 2021

Carbon dioxide (CO2) and carbonates, which are widely distributed in nature, are constituents of inorganic and organic matter and are essential in vegetable and animal organisms. CO2 is the principal greenhouse gas in the atmosphere. In human blood, CO2/HCO3− is an important buffering system. Inorganic nitrate (ONO2−) and nitrite (ONO−) are major metabolites and abundant reservoirs of nitric oxide (NO), an endogenous multifunctional signaling molecule. Carbonic anhydrase (CA) is involved in the reabsorption of nitrite and nitrate from the primary urine. The measurement of nitrate and nitrite in biological samples is of particular importance. The derivatization of nitrate and nitrite in biological samples alongside their 15N-labeled analogs, which serve as internal standards, is a prerequisite for their analysis by gas chromatography–mass spectrometry (GC-MS). A suitable derivatization reagent is pentafluorobenzyl bromide (PFB-Br). Nitrate and nitrite are converted in aqueous acetone to PFB-ONO2 and PFB-NO2, respectively. PFB-Br is also useful for the GC-MS analysis of carbonate/bicarbonate. This is of particular importance in conditions of pharmacological CA inhibition, for instance by acetazolamide, which is accompanied by elevated concomitant excretion of nitrate, nitrite and bicarbonate, as well as by urine alkalization. We performed a series of experiments with exogenous bicarbonate (NaHCO3) added to human urine samples (range, 0 to 100 mM), as well as with endogenous bicarbonate resulting from the inhibition of CA activity in healthy subjects before and after ingestion of pharmacological acetazolamide. Our results indicate that bicarbonate enhances the derivatization of nitrate with PFB-Br. In contrast, bicarbonate decreases the derivatization of nitrite with PFB-Br. Bicarbonate is not a catalyst, but it enhances PFB-ONO2 formation and inhibits PFB-NO2 formation in a concentration-dependent manner. The effects of bicarbonate are likely to result from its reaction with PFB-Br to generate PFB-OCOOH. Nitrate reacts with concomitantly produced PFB-OCOOH to form PFB-ONO2 in addition to the direct reaction of nitrate with PFB-Br. By contrast, nitrite does not react with PFB-OCOOH to form PFB-NO2. Sample acidification by small volumes of 20 wt.% aqueous acetic acid abolishes the effects of exogenous and endogenous bicarbonate on nitrite measurement.
Review of Nephelium lappaceum and Nephelium ramboutan-ake: A High Potential Supplement
Authors: Tsong Jia Ling , Goh Lucky Poh Wah , Gansau Jualang Azlan , How Siew-Eng
Published: November 2021

Nephelium lappaceum (N. lappaceum) and Nephelium ramboutan-ake (N. ramboutan-ake) are tropical fruits that gain popularity worldwide due to their tastiness. Currently, their potential to be used as pharmaceutical agents is underestimated. Chronic diseases such as cancer, diabetes and aging have high incidence rates in the modern world. Furthermore, pharmaceutical agents targeting pathogenic microorganisms have been hampered by the growing of antimicrobial resistance threats. The idea of food therapy leads to extensive nutraceuticals research on the potential of exotic fruits such as N. lappaceum and N. ramboutan-ake to act as supplements. Phytochemicals such as phenolic compounds that present in the fruit act as potent antioxidants that contribute to the protective effects against diseases induced by oxidative stress. Fruit residuals such as the peel and seeds hold greater nutraceutical potential than the edible part. This review highlights the antioxidant and biological activities (anti-neoplastic, anti-microbial, hypoglycemic actions and anti-aging), and chemical contents of different parts of N. lappaceum and N. ramboutan-ake. These fruits contain a diverse and important chemical profile that can alleviate or cure diseases.
Hetero-Type Benzannulation Leading to Substituted Benzothio-Phenes
Authors: Kono Taro , Sasaki Ryosuke , Goto Hideki , Kakuno Masatoshi , Tanabe Yoo
Published: November 2021

TiCl4 (or SnCl4)-promoted hetero-type benzannulation reactions using various (2,2-dichlorocyclopropyl)(thiophen-2-yl)methanols proceeded smoothly to produce uniquely substituted 4-chlorobenzothiophenes (five examples). The present approach involves the first distinctive thiophene formation from thiophene cores, in contrast to traditional methods of thiophene formation from benzene cores. The stereocongested (less reactive) Cl position in the obtained 4-chlorobenzothiophenes functioned successfully as the partners of three cross-coupling reactions: (i) a Suzuki–Miyaura cross-couplings using Pd(OAc)2/SPhos/K3PO4 catalysis (seven examples; 63–91%), (ii) a hydroxylation using KOH/Pd(dba)2/tBu-XPhos catalysis (85%), and (iii) a borylation using a B2(pin)2/Pd(dba)2/XPhos/NaOAc catalysis-provided 4-(pin)B-benzothiophene (58%).
Solid-Phase Synthesis of Selectively Mono-Fluorobenz(o)ylated Polyamines as a Basis for the Development of 18F-Labeled Radiotracers
Authors: Wodtke Robert , Pietzsch Jens , Löser Reik
Published: November 2021

Polyamines are highly attractive vectors for tumor targeting, particularly with regards to the development of radiolabeled probes for imaging by positron emission (PET) and single-photon emission computed tomography (SPECT). However, the synthesis of selectively functionalized derivatives remains challenging due to the presence of multiple amino groups of similar reactivity. In this work, we established a synthetic methodology for the selective mono-fluorobenz(o)ylation of various biogenic diamines and polyamines as lead compounds for the perspective development of substrate-based radiotracers for targeting polyamine-specific membrane transporters and enzymes such as transglutaminases. For this purpose, the polyamine scaffold was constructed by solid-phase synthesis of the corresponding oxopolyamines and subsequent reduction with BH3/THF. Primary and secondary amino groups were selectively protected using Dde and Boc as protecting groups, respectively, in orientation to previously reported procedures, which enabled the selective introduction of the reporter groups. For example, N1-FBz-spermidine, N4-FBz-spermidine, N8-FBz-spermidine, and N1-FBz-spermine and N4-FBz-spermine (FBz = 4-fluorobenzoyl) were obtained in good yields by this approach. The advantages and disadvantages of this synthetic approach are discussed in detail and its suitability for radiolabeling was demonstrated for the solid-phase synthesis of N1-[18F]FBz-cadaverine.
Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors
Authors: Angeli Andrea , Kartsev Victor , Petrou Anthi , Pinteala Mariana , Brovarets Volodymyr , Vydzhak Roman , Panchishin Svitlana , Geronikaki Athina , Supuran Claudiu T.
Published: November 2021

A series of benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with several bulky moieties has been obtained by original procedures. The new derivatives were investigated for the inhibition of four physiologically crucial human carbonic anhydrase (hCA, EC 4.2.2.1.1) isoforms, hCA I and II (cytosolic enzymes) as well as hCA IX and XII (transmembrane, tumor-associated isoforms). Examples of isoform-selective inhibitors were obtained for all four enzymes investigated here, and a computational approach was employed for explaining the observed selectivity, which may be useful in drug design approaches for obtaining inhibitors with pharmacological applications useful as antiglaucoma, diuretic, antitumor or anti-cerebral ischemia drugs.
Corrosion Inhibition Using Harmal Leaf Extract as an Eco-Friendly Corrosion Inhibitor
Authors: Al Otaibi Nasreen , Hammud Hassan H.
Published: November 2021

Extract of natural plants is one of the most important metallic corrosion inhibitors. They are readily available, nontoxic, environmentally friendly, biodegradable, highly efficient, and renewable. The present project focuses on the corrosion inhibition effects of Peganum Harmala leaf extract. The equivalent circuit with two time constants with film and charge transfer components gave the best fitting of impedance data. Extraction of active species by sonication proved to be an effective new method to extract the inhibitors. High percent inhibition efficacy IE% of 98% for 283.4 ppm solutions was attained using impedance spectroscopy EIS measurements. The values of charge transfer Rct increases while the double layer capacitance Cdl values decrease with increasing Harmal extract concentration. This indicates the formation of protective film. The polarization curves show that the Harmal extract acts as a cathodic-type inhibitor. It is found that the adsorption of Harmal molecules onto the steel surface followed Langmuir isotherm. Fourier-transform infrared spectroscopy FTIR was used to determine the electron-rich functional groups in Harmal extract, which contribute to corrosion inhibition effect. Scanning electron microscopy SEM measurement of a steel surface clearly proves the anticorrosion effect of Harmal leaves.
Cyclometalated Iridium(III) Complex–Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular Ca2+ Overload from the Endoplasmic Reticulum and a Decrease in Mitochondrial Membrane Potential
Authors: Balachandran Chandrasekar , Yokoi Kenta , Naito Kana , Haribabu Jebiti , Tamura Yuichi , Umezawa Masakazu , Tsuchiya Koji , Yoshihara Toshitada , Tobita Seiji , Aoki Shin
Published: November 2021

In our previous paper, we reported that amphiphilic Ir complex–peptide hybrids (IPHs) containing basic peptides such as KK(K)GG (K: lysine, G: glycine) (e.g., ASb-2) exhibited potent anticancer activity against Jurkat cells, with the dead cells showing a strong green emission. Our initial mechanistic studies of this cell death suggest that IPHs would bind to the calcium (Ca2+)–calmodulin (CaM) complex and induce an overload of intracellular Ca2+, resulting in the induction of non-apoptotic programmed cell death. In this work, we conduct a detailed mechanistic study of cell death induced by ASb-2, a typical example of IPHs, and describe how ASb-2 induces paraptotic programmed cell death in a manner similar to that of celastrol, a naturally occurring triterpenoid that is known to function as a paraptosis inducer in cancer cells. It is suggested that ASb-2 (50 µM) induces ER stress and decreases the mitochondrial membrane potential (ΔΨm), thus triggering intracellular signaling pathways and resulting in cytoplasmic vacuolization in Jurkat cells (which is a typical phenomenon of paraptosis), while the change in ΔΨm values is negligibly induced by celastrol and curcumin. Other experimental data imply that both ASb-2 and celastrol induce paraptotic cell death in Jurkat cells, but this induction occurs via different signaling pathways.
Ancient Wheat and Quinoa Flours as Ingredients for Pasta Dough—Evaluation of Thermal and Rheological Properties
Authors: Gałkowska Dorota , Witczak Teresa , Witczak Mariusz
Published: November 2021

The aim of this study was to investigate thermal and rheological properties of selected ancient grain flours and to evaluate rheological properties of mixtures thereof represented by pasta dough and dry pasta. Flours from spelt, einkorn, and emmer ancient wheat varieties were combined with quinoa flour. All these flour sources are considered healthy grains of high bioactive component content. Research results were compared to durum wheat flour or spelt wheat flour systems. Differential scanning calorimeter (DSC) and a rapid visco analyzer (RVA) were used to investigate the phase transition behavior of the flours and pasting characteristics of the flours and dried pasta. Angular frequency sweep experiments and creep and recovery tests of the pasta dough were performed. The main components modifying the pasta dough structure were starch and water. Moreover, the proportion of the individual flours influenced the rheological properties of the dough. The durum wheat dough was characterized by the lowest values of the K′ and K″ parameters of the power law models (24,861 Pa·sn′ and 10,687 Pa·sn″, respectively) and the highest values of the instantaneous (J0) and retardation (J1) compliances (0.453 × 10−4 Pa and 0.644 × 10−4 Pa, respectively). Replacing the spelt wheat flour with the other ancient wheat flours and quinoa flour increased the proportion of elastic properties and decreased values of the J0 and J1 of the pasta dough. Presence of the quinoa flour increased pasting temperature (from 81.4 up to 83.3 °C) and significantly influenced pasting viscosities of the spelt wheat pasta samples. This study indicates a potential for using mixtures of spelt, einkorn, and emmer wheat flours with quinoa flour in the production of innovative pasta dough and pasta products.
Peroxymonosulfate Activation by Bi2WO6/BiOCl Heterojunction Nanocomposites under Visible Light for Bisphenol A Degradation
Authors: Huang Yongkui , Yin Xiangyang , He Pei , Kou Shuangwu , Zhang Xiaoting , Wang Lei , Lu Peili
Published: November 2021

The combination of peroxymonosulfate (PMS) activation and photocatalysis has proven to be effective for organic contaminants treatment. However, the construction of an efficient catalytic material is an important challenge. Herein, novel Bi2WO6/BiOCl heterojunction nanocomposites were successfully designed and fabricated using a facile and effective strategy for bisphenol A (BPA) photodegradation with PMS activation. The well-designed heterojunction with improvement of the contact area and interface microstructure was obtained through in situ growth of the Bi2WO6 on the surface of BiOCl. The Bi2WO6/BiOCl nanocomposites exhibit excellent catalytic performance in PMS activation for BPA degradation under visible light irradiation. A possible photocatalytic reaction mechanism was systematically revealed. The excellent catalytic performance is mainly attributed to the strong interaction between Bi2WO6 and BiOCl, resulting in an enhanced photoabsorption and a more efficient interfacial charge separation and transfer. This paper provides a novel strategy to design efficient catalytic materials for organic contaminants remediation with PMS activation.
Solution Blow Spun Silica Nanofibers: Influence of Polymeric Additives on the Physical Properties and Dye Adsorption Capacity
Authors: Farias Rosiane Maria da Costa , Severo Lucas Leite , Klamczynski Artur P. , Medeiros Eliton Souto de , Santana Lisiane Navarro de Lima , Neves Gelmires de Araújo , Glenn Gregory Melvin , Menezes Romualdo Rodrigues
Published: November 2021

The physical properties of porous silica nanofibers are an important factor that impacts their performance in various applications. In this study, porous silica nanofibers were produced via solution blow spinning (SBS) from a silica precursor/polymer solution. Two polyvinylpyrrolidone (PVP, Mw = 360,000 and 1,300,000) were chosen as spinning aids in order to create different pore properties. The effect of their physical properties on the adsorption of methylene blue (MB) in an aqueous solution was explored. After forming, the nanofibers were calcined to remove the organic phase and create pores. The calcined nanofibers had a large amount of micro and mesopores without the use of additional surfactants. The molecular weight of the PVP impacted the growth of silica particles and consequently the pore size. High Mw PVP inhibited the growth of silica particles, resulting in a large volume of micropores. On the other hand, silica nanofibers with a high fraction of mesopores were obtained using the lower Mw PVP. These results demonstrate a simple method of producing blow spun silica nanofibers with defined variations of pore sizes by varying only the molecular weight of the PVP. In the adsorption process, the accessible mesopores improved the adsorption performance of large MB molecules.
Vertically Aligned n-Type Silicon Nanowire Array as a Free-Standing Anode for Lithium-Ion Batteries
Authors: Nugroho Andika Pandu , Hawari Naufal Hanif , Prakoso Bagas , Refino Andam Deatama , Yulianto Nursidik , Iskandar Ferry , Kartini Evvy , Peiner Erwin , Wasisto Hutomo Suryo , Sumboja Afriyanti
Published: November 2021

Due to its high theoretical specific capacity, a silicon anode is one of the candidates for realizing high energy density lithium-ion batteries (LIBs). However, problems related to bulk silicon (e.g., low intrinsic conductivity and massive volume expansion) limit the performance of silicon anodes. In this work, to improve the performance of silicon anodes, a vertically aligned n-type silicon nanowire array (n-SiNW) was fabricated using a well-controlled, top-down nano-machining technique by combining photolithography and inductively coupled plasma reactive ion etching (ICP-RIE) at a cryogenic temperature. The array of nanowires ~1 µm in diameter and with the aspect ratio of ~10 was successfully prepared from commercial n-type silicon wafer. The half-cell LIB with free-standing n-SiNW electrode exhibited an initial Coulombic efficiency of 91.1%, which was higher than the battery with a blank n-silicon wafer electrode (i.e., 67.5%). Upon 100 cycles of stability testing at 0.06 mA cm−2, the battery with the n-SiNW electrode retained 85.9% of its 0.50 mAh cm−2 capacity after the pre-lithiation step, whereas its counterpart, the blank n-silicon wafer electrode, only maintained 61.4% of 0.21 mAh cm−2 capacity. Furthermore, 76.7% capacity retention can be obtained at a current density of 0.2 mA cm−2, showing the potential of n-SiNW anodes for high current density applications. This work presents an alternative method for facile, high precision, and high throughput patterning on a wafer-scale to obtain a high aspect ratio n-SiNW, and its application in LIBs.
High Adherence to Mediterranean Diet Is Not Associated with an Improved Sodium and Potassium Intake
Authors: Viroli Giulia , Gonçalves Carla , Pinho Olívia , Silva-Santos Tânia , Padrão Patrícia , Moreira Pedro
Published: November 2021

Prevention and control of hypertension and cerebro-cardiovascular diseases are associated with adequate sodium and potassium intake and adherence to a Mediterranean dietary pattern. The aim of this study was to assess the association between adherence to a Mediterranean diet (MD) and the excretion of sodium and potassium as surrogate measures of intake. This is a cross-sectional analysis as part of a larger study (the iMC SALT randomized controlled trial) among workers of a public university. A food frequency questionnaire was used to assess the adherence to MD, using the alternative Mediterranean diet (aMED) score; sodium and potassium excretions were estimated by 24-h urine collections. Sociodemographic and other lifestyle characteristics were also obtained. The associations between the adherence to MD and Na and K excretion were calculated by logistic regression, adjusting for confounding variables. From the 109 selected participants, seven were excluded considering urine screening and completeness criteria, leaving a final sample of 102 subjects (48% male, average age 47 years). Mean sodium and potassium excretion were 3216 mg/day and 2646 mg/day, respectively. Sodium and potassium excretion were significantly higher in men, but no differences were found according to different levels of MD adherence. In logistic regression analysis, sodium, potassium, and sodium-to-potassium ratio urinary excretion tertiles were not associated with MD adherence (low/moderate versus high), even after adjustment for confounding variables. A high adherence to MD was thus not associated with a different level of sodium and potassium intake.
Validity of FFQ Estimates of Total Sugars, Added Sugars, Sucrose and Fructose Compared to Repeated 24-h Recalls in Adventist Health Study-2 Participants
Authors: Peralta Mericarmen , Heskey Celine , Shavlik David , Knutsen Synnove , Mashchak Andrew , Jaceldo-Siegl Karen , Fraser Gary E. , Orlich Michael J.
Published: November 2021

Sugar intake is a potentially important aspect of diet which has not previously been validated in the Adventist Health Study-2 (AHS-2). We sought to validate the food frequency questionnaire (FFQ) measurement of total sugars, added sugars, sucrose, and fructose against multiple 24-h dietary recalls (recalls) in AHS-2 participants. Food consumption data from a self-administered FFQ and six recalls from 904 participants were combined with nutrient profile data to estimate daily sugar intake. Validity was evaluated among all participants and by race. FFQ and recall means were compared and correlation coefficients (Spearman’s, energy-adjusted log-transformed Pearson’s, deattenuated Pearson’s) were calculated. Mean total energy, total sugars, and fructose intake were higher in the FFQ, whereas added sugars and sucrose were higher in recalls. The energy-adjusted (log-transformed) deattenuated correlations among all participants were: total sugars (r = 0.42, 95% CI 0.32–0.52), added sugars (r = 0.50, 95% CI 0.36–0.59), sucrose (r = 0.32, 95% CI 0.23–0.42), and fructose (r = 0.50, 95% CI 0.40–0.59). We observed moderate validity for added sugars and fructose and low-moderate validity for total sugars and sucrose measured by the AHS-2 FFQ in this population. Dietary sugar estimates from this FFQ may be useful in assessing possible associations of sugars intake with health outcomes.
Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes
Authors: Bell Emily , Binkowski Sabrina , Sanderson Elaine , Keating Barbara , Smith Grant , Harray Amelia J. , Davis Elizabeth A.
Published: November 2021

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8–15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.
Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
Authors: Buko Vyacheslav , Zavodnik Ilya , Budryn Grażyna , Zakłos-Szyda Małgorzata , Belonovskaya Elena , Kirko Siarhei , Żyżelewicz Dorota , Zakrzeska Agnieszka , Bakunovich Aliaksei , Rusin Viktor , Moroz Valentina
Published: November 2021

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.
Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review
Authors: Keeler Johanna Louise , Treasure Janet , Juruena Mario F. , Kan Carol , Himmerich Hubertus
Published: November 2021

Anorexia nervosa (AN) is a highly complex disorder to treat, especially in severe and enduring cases. Whilst the precise aetiology of the disorder is uncertain, malnutrition and weight loss can contribute to reductions in grey and white matter of the brain, impairments in neuroplasticity and neurogenesis and difficulties with cognitive flexibility, memory and learning. Depression is highly comorbid in AN and may be a barrier to recovery. However, traditional antidepressants are often ineffective in alleviating depressive symptoms in underweight patients with AN. There is an urgent need for new treatment approaches for AN. This review gives a conceptual overview for the treatment of AN with ketamine. Ketamine has rapid antidepressant effects, which are hypothesised to occur via increases in glutamate, with sequelae including increased neuroplasticity, neurogenesis and synaptogenesis. This article provides an overview of the use of ketamine for common psychiatric comorbidities of AN and discusses particular safety concerns and side effects. Potential avenues for future research and specific methodological considerations are explored. Overall, there appears to be ample theoretical background, via several potential mechanisms, that warrant the exploration of ketamine as a treatment for adults with AN.
The Influence of Age and Oral Health on Taste Perception in Older Adults: A Case-Control Study
Authors: Alia Sonila , Aquilanti Luca , Pugnaloni Sofia , Di Paolo Alice , Rappelli Giorgio , Vignini Arianna
Published: November 2021

Declining gustatory function, nutrition, and oral health are important elements of health in older adults that can affect the aging process. The aim of the present work was to investigate the effect of age and oral status on taste discrimination in two different groups of elderly subjects living either in an Italian residential institution (TG) or in the community (CG). A total of 90 subjects were enrolled in the study (58 CG vs. 32 TG). Masticatory performance (MP) was assessed using the two-color mixing ability test. Taste function was evaluated using cotton pads soaked with six taste stimuli (salty, acid, sweet, bitter, fat and water). A positive correlation between age and missing teeth (r = 0.51, C.I. [0.33; 0.65], p < 0.0001), and a negative correlation between age and MP (r = −0.39, C.I. [−0.56; −0.20], p < 0.001) were found. Moreover, significant differences for salty taste, between TG and CG were detected (p < 0.05). Significant differences in bitter taste sensitivity between subjects wearing removable and non-removable prosthesis were also determined (p < 0.05). In addition, significant gender differences and between males in TG and CG were identified (p < 0.05). The best understanding of the relationship between MP, taste sensitivity, and nutritional factors is a necessary criterion for the development of new therapeutic strategies to address more effectively the problems associated with malnutrition in elderly subjects.
The Interplay between Salmonella and Intestinal Innate Immune Cells in Chickens
Authors: Ijaz Adil , Veldhuizen Edwin J. A. , Broere Femke , Rutten Victor P. M. G. , Jansen Christine A.
Published: November 2021

Salmonellosis is a common infection in poultry, which results in huge economic losses in the poultry industry. At the same time, Salmonella infections are a threat to public health, since contaminated poultry products can lead to zoonotic infections. Antibiotics as feed additives have proven to be an effective prophylactic option to control Salmonella infections, but due to resistance issues in humans and animals, the use of antimicrobials in food animals has been banned in Europe. Hence, there is an urgent need to look for alternative strategies that can protect poultry against Salmonella infections. One such alternative could be to strengthen the innate immune system in young chickens in order to prevent early life infections. This can be achieved by administration of immune modulating molecules that target innate immune cells, for example via feed, or by in-ovo applications. We aimed to review the innate immune system in the chicken intestine; the main site of Salmonella entrance, and its responsiveness to Salmonella infection. Identifying the most important players in the innate immune response in the intestine is a first step in designing targeted approaches for immune modulation.
Modulation of Production of Th1/Th2 Cytokines in Peripheral Blood Mononuclear Cells and Neutrophils by Hepatitis C Virus Infection in Chronically Infected Patients
Authors: Essa Sahar , Siddique Iqbal , Saad Motaz , Raghupathy Raj
Published: November 2021

This study investigated the influence of Hepatitis C virus (HCV) infection on the cytokine production profiles of the peripheral blood monoculear cells (PBMC) and neutrophils in chronically naïve HCV-infected patients. Seventy-five genotype-4 naïve HCV-infected patients (HCV+) and healthy subjects (HCV−) were enrolled. The neutrophils and the PBMC were separated by density gradient sedimentation and stimulated with a mitogen. The culture supernatants were evaluated for levels of IFN-α, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, and TNF-α using anti-cytokine antibody MACSPlex capture beads. The PBMC cytokine profiles of HCV+ patients showed significantly lower mean values for IFN-γ, IL-2, IL-6, IL-9, and IL-10 (p < 0.0001) as compared to HCV− subjects. In contrast, HCV+ patients showed higher mean levels of PBMC cytokine values for IL-5 and TNF-α (p < 0.0001). As for neutrophils, HCV+ patients showed significantly lower mean levels of IFN-α, IFN-γ, IL-2, IL-4, IL-6, IL-9, and IL-10 (p < 0.0001). In contrast, the neutrophils from HCV+ patients showed higher mean levels of IL-5, IL-12, and TNF-α (p < 0.0001). Th1–Th2 cytokine ratios suggested a lower Th1 bias in HCV+ subjects as compared to HCV− subjects. Our results suggest that chronic HCV infection brings about an immunomodulatory effect not only on neutrophils, but also to a lower extent on PBMCs
Pharmacological and Epigenetic Regulators of NLRP3 Inflammasome Activation in Alzheimer’s Disease
Authors: La Rosa Francesca , Mancuso Roberta , Agostini Simone , Piancone Federica , Marventano Ivana , Saresella Marina , Hernis Ambra , Fenoglio Chiara , Galimberti Daniela , Scarpini Elio , Clerici Mario
Published: November 2021

Activation of the NLRP3 inflammasome complex results in the production of IL-18, Caspase-1 and IL-1β. These cytokines have a beneficial role in promoting inflammation, but an excessive activation of the inflammasome and the consequent constitutive inflammatory status is a negative factor in human pathologies including Alzheimer’s Disease (AD). MicroRNAs (miR-NAs) target the 3′UTR region of NLRP3, preventing the activation of the inflammasome and inhibiting cytokine production. Because Stavudine (D4T), an antiretroviral drug, was recently shown to reduce inflammasome activation, we verified whether its effect is mediated by miR-7-5p, miR-22-3p, miR-30e-5p and miR-223-3p: miRNAs that bind the NLRP3-mRNA-UTR region and interfere with protein translation, reducing NLRP3 activation. Peripheral blood mononuclear cells (PBMCs) of twenty AD patients and ten sex-matched Healthy Controls (HC) were stimulated with Lipopolysaccharides (LPS)+Amyloid-beta (Aβ42) in the absence/presence of D4T. Expression of genes within the inflammasome complex and of miRNAs was evaluated by RT-PCR; cytokines and caspase-1 production was measured by ELISA. Results have shown that: NLRP3, ASC, IL-1β and IL-18 expression, as well as IL-18, IL-1β and caspase-1 production, were significantly augmented (p < 0.05) in LPS+Aβ42-stimulated PBMCs of AD patients compared to HC. D4T reduced the expression of inflammasome genes and cytokine production (p < 0.005). miR-7-5p and miR-223-3p expression was significantly increased in LPS+Aβ42-stimulated PBMCs of AD patients (p < 0.05), and it was reduced by D4T in AD alone. In conclusion: miR-223-3p and mir-7-5p expression is increased in AD, but this does not result in down-regulation of NLRP3 inflammasome expression and of IL-1β and IL-18 production. D4T increased miRNA expression in HC but had an opposite effect in AD, suggesting that miRNA regulatory mechanisms are altered in AD.
Structural Studies of β-Diketones and Their Implications on Biological Effects
Authors: Hansen Poul Erik
Published: November 2021

The paper briefly summarizes methods to determine the structure of β-diketones with emphasis on NMR methods. Density functional calculations are also briefly treated. Emphasis is on the tautomeric equilibria of β-diketones in relation to biological effects. Relevant physical parameters such as acidity and solubility are treated. A series of biologically active molecules are treated with respect to structure (tautomerism). Characteristic molecules or groups of molecules are usnic acids, tetramic and tetronic acids, o-hydroxydibenzoylmethanes, curcumines, lupulones, and hyperforines.
SapC–DOPS as a Novel Therapeutic and Diagnostic Agent for Glioblastoma Therapy and Detection: Alternative to Old Drugs and Agents
Authors: Kaynak Ahmet , Davis Harold W. , Vallabhapurapu Subrahmanya D. , Pak Koon Y. , Gray Brian D. , Qi Xiaoyang
Published: November 2021

Glioblastoma multiforme (GBM), the most common type of brain cancer, is extremely aggressive and has a dreadful prognosis. GBM comprises 60% of adult brain tumors and the 5 year survival rate of GBM patients is only 4.3%. Standard-of-care treatment includes maximal surgical removal of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. TMZ is the “gold-standard” chemotherapy for patients suffering from GBM. However, the median survival is only about 12 to 18 months with this protocol. Consequently, there is a critical need to develop new therapeutic options for treatment of GBM. Nanomaterials have unique properties as multifunctional platforms for brain tumor therapy and diagnosis. As one of the nanomaterials, lipid-based nanocarriers are capable of delivering chemotherapeutics and imaging agents to tumor sites by enhancing the permeability of the compound through the blood–brain barrier, which makes them ideal for GBM therapy and imaging. Nanocarriers also can be used for delivery of radiosensitizers to the tumor to enhance the efficacy of the radiation therapy. Previously, high-atomic-number element-containing particles such as gold nanoparticles and liposomes have been used as radiosensitizers. SapC–DOPS, a protein-based liposomal drug comprising the lipid, dioleoylphosphatidylserine (DOPS), and the protein, saposin C (SapC), has been shown to be effective for treatment of a variety of cancers in small animals, including GBM. SapC–DOPS also has the unique ability to be used as a carrier for delivery of radiotheranostic agents for nuclear imaging and radiotherapeutic purposes. These unique properties make tumor-targeting proteo-liposome nanocarriers novel therapeutic and diagnostic alternatives to traditional chemotherapeutics and imaging agents. This article reviews various treatment modalities including nanolipid-based delivery and therapeutic systems used in preclinical and clinical trial settings for GBM treatment and detection.
GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35
Authors: De Masi Roberto , Orlando Stefania
Published: November 2021

Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1). We found GANAB to be 2.51-fold downregulated in the IFN-treated group with respect to the untreated one (p < 0.0001) and 3.39-fold downregulated in responder patients compared to the non-responders (p < 0.0001). GANAB correlated directly with RS (r = 0.8088, p < 0.0001) and lesion load (LL) (r = 0.5824, p = 0.0014) in the IFN-treated group and inversely with disease duration (DD) (r = −0.6081, p = 0.0096) in the untreated one. Lower mean values were expressed for GANAB than IFI35 in IFN responder (p < 0.0001) and higher mean values in the non-responder patients (p = 0.0022). Inverse correlations were also expressed with IFI35 in the overall patient population (r = −0.6468, p < 0.0001). In conclusion, the modular expression of GANAB reflects IFI35, RS, DD, and LL values, making it a biomarker of neuroinflammation that is predictive for disease activity and treatment response in MS.
Topical Delivery of Niacinamide to Skin Using Hybrid Nanogels Enhances Photoprotection Effect
Authors: Basto Renata , Andrade Raquel , Nunes Cláudia , Lima Sofia A. Costa , Reis Salette
Published: November 2021

Niacinamide (NIA) has been widely used in halting the features of ageing by acting as an antioxidant and preventing dehydration. NIA’s physicochemical properties suggest difficulties in surpassing the barrier imposed by the stratum corneum layer to reach the target in the skin. To improve cutaneous delivery of NIA, a hybrid nanogel was designed using carrageenan and polyvinylpyrrolidone polymers combined with jojoba oil as a permeation enhancer. Three different types of transethosomes were prepared by the thin-film hydration method, made distinct by the presence of either an edge activator or a permeation enhancer, to allow for a controlled delivery of NIA. Formulations were characterized by measurements of size, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity, and by evaluating their chemical interactions and morphology. Skin permeation assays were performed using Franz diffusion cells. The hybrid hydrogels exhibited robust, porous, and highly aligned macrostructures, and when present, jojoba oil changed their morphology. Skin permeation studies with transethosomes-loaded hydrogels showed that nanogels per se exhibit a more controlled and enhanced permeation, in particular when jojoba oil was present in the transethosomes. These promising nanogels protected the human keratinocytes from UV radiation, and thus can be added to sunscreens or after-sun lotions to improve skin protection.
Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model
Authors: Madžarević Marijana , Medarević Đorđe , Pavlović Stefan , Ivković Branka , Đuriš Jelena , Ibrić Svetlana
Published: November 2021

Selective laser sintering (SLS) is a rapid prototyping technique for the production of three-dimensional objects through selectively sintering powder-based layer materials. The aim of the study was to investigate the effect of energy density (ED) and formulation factors on the printability and characteristics of SLS irbesartan tablets. The correlation between formulation factors, ED, and printability was obtained using a decision tree model with an accuracy of 80%. FT-IR results revealed that there was no interaction between irbesartan and the applied excipients. DSC results indicated that irbesartan was present in an amorphous form in printed tablets. ED had a significant influence on tablets’ physical, mechanical, and morphological characteristics. Adding lactose monohydrate enabled faster drug release while reducing the possibility for printing with different laser speeds. However, formulations with crospovidone were printable with a wider range of laser speeds. The adjustment of formulation and process parameters enabled the production of SLS tablets with hydroxypropyl methylcellulose with complete release in less than 30 min. The results suggest that a decision tree could be a useful tool for predicting the printability of pharmaceutical formulations. Tailoring the characteristics of SLS irbesartan tablets by ED is possible; however, it needs to be governed by the composition of the whole formulation.
Smart Nanotherapeutics and Lung Cancer
Authors: Doroudian Mohammad , Azhdari Mohammad H. , Goodarzi Nima , O’Sullivan David , Donnelly Seamas C.
Published: November 2021

Lung cancer is a significant health problem worldwide. Unfortunately, current therapeutic strategies lack a sufficient level of specificity and can harm adjacent healthy cells. Consequently, to address the clinical need, novel approaches to improve treatment efficiency with minimal side effects are required. Nanotechnology can substantially contribute to the generation of differentiated products and improve patient outcomes. Evidence from previous research suggests that nanotechnology-based drug delivery systems could provide a promising platform for the targeted delivery of traditional chemotherapeutic drugs and novel small molecule therapeutic agents to treat lung cancer cells more effectively. This has also been found to improve the therapeutic index and reduce the required drug dose. Nanodrug delivery systems also provide precise control over drug release, resulting in reduced toxic side effects, controlled biodistribution, and accelerated effects or responses. This review highlights the most advanced and novel nanotechnology-based strategies, including targeted nanodrug delivery systems, stimuli-responsive nanoparticles, and bio-nanocarriers, which have recently been employed in preclinical and clinical investigations to overcome the current challenges in lung cancer treatments.
Genetic Polymorphisms Affecting Ranibizumab Response in High Myopia Patients
Authors: Blánquez-Martínez David , Díaz-Villamarín Xando , Antúnez-Rodríguez Alba , Pozo-Agundo Ana , Muñoz-Ávila José Ignacio , Martínez-González Luis Javier , Dávila-Fajardo Cristina Lucía
Published: November 2021

High myopia is an ophthalmic pathology that affects half of the young adults in the United States and Europe and it is predicted that a third of the world’s population could be nearsighted at the end of this decade. It is characterized by at least 6 diopters or axial length > 26 mm and, choroidal neovascularization (CNV) in 5 to 11% of cases. Ranibizumab is a recombinant humanized monoclonal antibody fragment. It is an anti-vascular endothelial growth factor (anti-VEGF) drug used in the treatment of CNV. Many genetic polymorphisms have been associated with interindividual differences in the response to ranibizumab, but these associations were not yet assessed among patients with high myopia and CNV. We performed a retrospective study assessing the association of genetic polymorphisms with response to ranibizumab in patients with CNV secondary to high myopia (mCNV). We included genetic polymorphisms previously associated with the response to drugs used in CNV patients (bevacizumab, ranibizumab, aflibercept, and photodynamic therapy (PDT)). We also included genetic variants in the VEGFA gene. Based on our results, ARMS2 (rs10490924) and CFH (rs1061170) are associated with response to ranibizumab in high myopia patients; and, included VEGFA genetic polymorphisms are not associated with ranibizumab response in our population but might be related to a higher risk of CNV.