bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry
Authors: Deprez Benoit , Bosc Damien , Charton Julie , Couturier Cyril , Deprez-Poulain Rebecca , Flipo Marion , Leroux Florence , Villemagne Baptiste , Willand Nicolas
Published: October 2021

Chemical biology and drug discovery are two scientific activities that pursue different goals but complement each other. The former is an interventional science that aims at understanding living systems through the modulation of its molecular components with compounds designed for this purpose. The latter is the art of designing drug candidates, i.e., molecules that act on selected molecular components of human beings and display, as a candidate treatment, the best reachable risk benefit ratio. In chemical biology, the compound is the means to understand biology, whereas in drug discovery, the compound is the goal. The toolbox they share includes biological and chemical analytic technologies, cell and whole-body imaging, and exploring the chemical space through state-of-the-art design and synthesis tools. In this article, we examine several tools shared by drug discovery and chemical biology through selected examples taken from research projects conducted in our institute in the last decade. These examples illustrate the design of chemical probes and tools to identify and validate new targets, to quantify target engagement in vitro and in vivo, to discover hits and to optimize pharmacokinetic properties with the control of compound concentration both spatially and temporally in the various biophases of a biological system.
Antioxidant and Anti-Inflammatory Effects of Peganum harmala Extracts: An In Vitro and In Vivo Study
Authors: Abbas Malik Waseem , Hussain Mazhar , Qamar Muhammad , Ali Sajed , Shafiq Zahid , Wilairatana Polrat , Mubarak Mohammad S.
Published: October 2021

Peganum harmala (P. harmala) belongs to the family Zygophyllaceae, and is utilized in the traditional medicinal systems of Pakistan, China, Morocco, Algeria, and Spain to treat several chronic health disorders. The aim of the present study was to identify the chemical constituents and to evaluate the antioxidant, anti-inflammatory, and toxicity effects of P. harmala extracts both in vitro and in vivo. Sequential crude extracts including 100% dichloromethane, 100% methanol, and 70% aqueous methanol were obtained and their antioxidant and anti-inflammatory effects evaluated both in vitro and in vivo. The anti-inflammatory effect of the extract was investigated using the carrageenan-induced paw edema method in mice, whereas the toxicity of the most active extract was evaluated using an acute and subacute toxicity rat model. In addition, we have used the bioassay-guided approach to obtain potent fractions, using solvent–solvent partitioning and reversed phase high performance liquid chromatography from active crude extracts; identification and quantification of compounds from the active fractions was achieved using electrospray ionization mass spectrometry and high performance liquid chromatography techniques. Results revealed that the 100% methanol extract of P. harmala exhibits significant in vitro antioxidant activity in DPPH assay with an IC50 of 49 µg/mL as compared to the standard quercetin with an IC50 of 25.4 µg/mL. The same extract exhibited 63.0% inhibition against serum albumin denaturation as compared to 97% inhibition by the standard diclofenac sodium in an in vitro anti-inflammatory assay, and in vivo anti-inflammatory against carrageenan-induced paw edema (75.14% inhibition) as compared to 86.1% inhibition caused by the standard indomethacin. Furthermore, this extract was not toxic during a 14 day trial of acute toxicity when given at a dose of 3 g/kg, indicating that the lethal dose (LD50) of P. harmala methanol extract was greater than 3 g/kg. P. harmala methanolic fraction 2 obtained using bioassay-guided fractionation showed the presence of quinic acid, peganine, harmol, harmaline, and harmine, confirmed by electrospray ionization mass spectrometry and quantified using external standards on high performance liquid chromatography. Taken all together, the current investigation further confirms the antioxidant, anti-inflammatory, and safety aspects of P. harmala, which justifies its use in folk medicine.
Development of Microchip Isotachophoresis Coupled with Ion Mobility Spectrometry and Evaluation of Its Potential for the Analysis of Food, Biological and Pharmaceutical Samples
Authors: Hradski Jasna , Ďuriš Marta , Szucs Roman , Moravský Ladislav , Matejčík Štefan , Masár Marián
Published: October 2021

An online coupling of microchip isotachophoresis (µITP) with ion mobility spectrometry (IMS) using thermal evaporation interface is reported for the first time. This combination integrates preconcentration power of the µITP followed by unambiguous identification of trace compounds in complex samples by IMS. Short-chain carboxylic acids, chosen as model analytes, were first separated by the µITP in a discontinuous electrolyte system at pH 5–6, and subsequently evaporated at 130 °C during their transfer to the IMS analyzer. Various parameters, affecting the transfer of the separated sample components through the evaporation system, were optimized to minimize dispersion and loss of the analytes as well as to improve sensitivity. The following analytical attributes were obtained for carboxylic acids in the standard solutions: 0.1–0.3 mg L−1 detection limits, 0.4–0.9 mg L−1 quantitation limits, linear calibration range from the quantitation limit to 75 mg L−1, 0.2–0.3% RSD of the IMS response and 98–102% accuracy. The analytical potential of the developed µITP-IMS combination was demonstrated on the analysis of various food, pharmaceutical and biological samples, in which the studied acids are naturally present. These include: apple vinegar, wine, fish sauce, saliva and ear drops. In the real samples, 0.3–0.6% RSD of the IMS response and 93–109% accuracy were obtained.
T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei
Authors: Silverberg Lee J. , Mal Tapas K. , Pacheco Carlos N. , Povelones Megan L. , Malfara Madeline F. , Lagalante Anthony F. , Olsen Mark A. , Yennawar Hemant P. , Sobhi Hany F. , Baney Kayla R. , Bozeman Robin L. , Eroh Craig S. , Fleming Michael J. , Garcia Tracy L. , Gregory Casey L. , Hahn Julia E. , Hatter Alyssa M. , Johns Lexi L. , Klinger Tianna L. , Li Jennie J. , Menig Andrew J. , Muench Grace C. , Ramirez Melissa E. , Reilly Jordyn , Sacco Nicole , Sheidy Alexandra M. , Stoner Marla M. , Thompson Eric N. , Yazdani Soroush F.
Published: October 2021

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.
Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens
Authors: Echigo Hiroaki , Mishiro Kenji , Fuchigami Takeshi , Shiba Kazuhiro , Kinuya Seigo , Ogawa Kazuma
Published: October 2021

We recently developed 125I- and 211At-labeled monomer RGD peptides using a novel radiolabeling method. Both labeled peptides showed high accumulation in the tumor and exhibited similar biodistribution, demonstrating their usefulness for radiotheranostics. This study applied the labeling method to a dimer RGD peptide with the aim of gaining higher accumulation in tumor tissues based on improved affinity with αvβ3 integrin. We synthesized an iodine-introduced dimer RGD peptide, E[c(RGDfK)] (6), and an 125/131I-labeled dimer RGD peptide, E[c(RGDfK)]{[125/131I]c[RGDf(4-I)K]} ([125/131I]6), and evaluated them as a preliminary step to the synthesis of an 211At-labeled dimer RGD peptide. The affinity of 6 for αvβ3 integrin was higher than that of a monomer RGD peptide. In the biodistribution experiment at 4 h postinjection, the accumulation of [125I]6 (4.12 ± 0.42% ID/g) in the tumor was significantly increased compared with that of 125I-labeled monomer RGD peptide (2.93 ± 0.08% ID/g). Moreover, the accumulation of [125I]6 in the tumor was greatly inhibited by co-injection of an excess RGD peptide. However, a single injection of [131I]6 (11.1 MBq) did not inhibit tumor growth in tumor-bearing mice. We expect that the labeling method for targeted alpha therapy with 211At using a dimer RGD peptide could prove useful in future clinical applications.
Rapid Screening Alpha-Glucosidase Inhibitors from Polygoni Vivipari Rhizoma by Multi-Step Matrix Solid-Phase Dispersion, Ultrafiltration and HPLC
Authors: Li Haoxiang , He Zhuobin , Shen Qianhui , Fan Weifeng , Tan Guoying , Zou Yuansheng , Mei Quanxi , Qian Zhengming
Published: October 2021

Polygoni Vivipari Rhizoma (PVR), the dried root of Polygonum viviparum, has been used as herbal medicine in China for a long time. In the present study, a new method based on multi-step matrix solid-phase dispersion (MSPD), ultrafiltration and high performance liquid chromatography (HPLC) for screening alpha-glucosidase inhibitors (AGIs) from PVR was proposed. First, three different PVR extractions were prepared by multi-step MSPD with 15% methanol, 60% methanol and 100% methanol. Second, the alpha-glucosidase inhibition tests for the three extracts were carried out, and the 60% methanol extraction showed the best activity. Then, the AGIs screening experiment was performed with ultrafiltration and HPLC analysis using the 60% methanol extraction. Seven binding components (quercetin−3−O−vicianoside, quercetin 3−O−neohesperidoside, rutin, hyperoside, quercetin 3−O−glucuronide, luteolin−7−O−neohesperidoside, kaempferol 3−glucuronide) were found. These seven components were further validated as the AGIs by molecular docking analysis. The developed method was a rapid and efficient tool for screening AGIs from PVR, which provided scientific data for the bioactive components study of PVR.
Synthesis of Porous Material from Coal Gasification Fine Slag Residual Carbon and Its Application in Removal of Methylene Blue
Authors: Zhang Yixin , Wang Rumeng , Qiu Guofeng , Jia Wenke , Guo Yang , Guo Fanhui , Wu Jianjun
Published: October 2021

A large amount of coal gasification slag is produced every year in China. However, most of the current disposal is into landfills, which causes serious harm to the environment. In this research, coal gasification fine slag residual carbon porous material (GFSA) was prepared using gasification fine slag foam flotation obtained carbon residue (GFSF) as raw material and an adsorbent to carry out an adsorption test on waste liquid containing methylene blue (MB). The effects of activation parameters (GFSF/KOH ratio mass ratio, activation temperature, and activation time) on the cation exchange capacity (CEC) of GFSA were investigated. The total specific surface area and pore volume of GSFA with the highest CEC were 574.02 m2/g and 0.467 cm3/g, respectively. The degree of pore formation had an important effect on CEC. The maximum adsorption capacity of GFSA on MB was 19.18 mg/g in the MB adsorption test. The effects of pH, adsorption time, amount of adsorbent, and initial MB concentration on adsorption efficiency were studied. Langmuir isotherm and quasi second-order kinetic model have a good fitting effect on the adsorption isotherm and kinetic model of MB.
The Procyanidin C1-Dependent Inhibition of the Hydrolysis of Potato Starch and Corn Starch Induced by Pancreatin
Authors: Takahama Umeo , Hirota Sachiko
Published: October 2021

Procyanidins are contained in various foods, and their effects on starch hydrolysis have been reported. In Japan, black soybeans, which contain a trimeric procyanidin, procyanidin C1 (proC1), are cooked with rice and used to prepare dumplings. In this study, the effects of proC1 on the pancreatin-induced formation of reducing sugars and starch hydrolysis were studied using potato starch and corn starch. ProC1 inhibited both reactions; the inhibition was greater in potato starch than corn starch when added to heated potato starch and corn starch. When heated with proC1, its inhibitory effects decreased, especially in potato starch, suggesting the important role of proC1 itself for the inhibition of potato starch hydrolysis. ProC1 also inhibited the hydrolysis when added to heated, longer amylose (average molecular weight: 31,200), and the inhibition decreased when heated with the amylose. On the other hand, proC1 could not inhibit the hydrolysis when added to heated, shorter amylose (average molecular weight: 4500), but could when heated with the amylose, suggesting the important role of the degradation products of proC1 for the inhibition. We discuss the mechanism of the proC1-dependent inhibition of amylose hydrolysis, taking the molecular weight into account.
Beneficial Effects of Green Tea EGCG on Skin Wound Healing: A Comprehensive Review
Authors: Xu Fa-Wei , Lv Ying-Li , Zhong Yu-Fan , Xue Ya-Nan , Wang Yong , Zhang Li-Yun , Hu Xian , Tan Wei-Qiang
Published: October 2021

Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.
Highly Porous Hydroxyapatite/Graphene Oxide/Chitosan Beads as an Efficient Adsorbent for Dyes and Heavy Metal Ions Removal
Authors: Hoa Nguyen Van , Minh Nguyen Cong , Cuong Hoang Ngoc , Dat Pham Anh , Nam Pham Viet , Viet Pham Hau Thanh , Phuong Pham Thi Dan , Trung Trang Si
Published: October 2021

Dye and heavy metal contaminants are mainly aquatic pollutants. Although many materials and methods have been developed to remove these pollutants from water, effective and cheap materials and methods are still challenging. In this study, highly porous hydroxyapatite/graphene oxide/chitosan beads (HGC) were prepared by a facile one-step method and investigated as efficient adsorbents. The prepared beads showed a high porosity and low bulk density. SEM images indicated that the hydroxyapatite (HA) nanoparticles and graphene oxide (GO) nanosheets were well dispersed on the CTS matrix. FT-IR spectra confirmed good incorporation of the three components. The adsorption behavior of the obtained beads to methylene blue (MB) and copper ions was investigated, including the effect of the contact time, pH medium, dye/metal ion initial concentration, and recycle ability. The HGC beads showed rapid adsorption, high capacity, and easy separation and reused due to the porous characteristics of GO sheets and HA nanoparticles as well as the rich negative charges of the chitosan (CTS) matrix. The maximum sorption capacities of the HGC beads were 99.00 and 256.41 mg g−1 for MB and copper ions removal, respectively.
Tilted Nano-Grating Based Ultra-Compact Broadband Polarizing Beam Splitter for Silicon Photonics
Authors: Liu Haipeng , Feng Jijun , Ge Jinman , Zhuang Shanqing , Yuan Shuo , Chen Yishu , Li Xiaojun , Tan Qinggui , Yu Qinghua , Zeng Heping
Published: October 2021

An ultra-compact broadband silicon polarizing beam splitter is proposed based on a tilted nano-grating structure. A light cross coupling can be realized for transverse-magnetic mode, while the transverse-electric light can almost completely output from the through port. The length of the coupling region is only 6.8 μm, while an extinction ratio of 23.76 dB can be realized at a wavelength of 1550 nm. As a proof of concept, the device was fabricated by a commercial silicon photonic foundry. It can realize a 19.84 dB extinction ratio and an 80 nm working bandwidth with an extinction ratio of larger than 10 dB. The presented device also shows a good fabrication tolerance to the structure deviations, which is favorable for its practical applications in silicon photonics.
Defective Black TiO2: Effects of Annealing Atmospheres and Urea Addition on the Properties and Photocatalytic Activities
Authors: Zhang Xu , Cai Min , Cui Naxin , Chen Guifa , Zou Guoyan , Zhou Li
Published: October 2021

A series of black TiO2 with and without the addition of urea were successfully prepared using a simple one-step synthetic method by calcination under different atmospheres (vacuum, He, or N2). The physicochemical, optical, and light-induced charge transfer properties of the as-prepared samples were characterized by various techniques. It was found that a vacuum atmosphere was more beneficial for the formation of oxygen vacancies (OVs) than the inert gases (He and N2) and the addition of urea-inhibited OVs formation. The samples annealed in the vacuum condition exhibited better visible-light adsorption abilities, narrower bandgaps, higher photo-induced charge separation efficiency, and lower recombination rates. Hydroxyl radicals (·OH) were the dominant oxidative species in the samples annealed under a vacuum. Finally, the samples annealed under vacuum conditions displayed higher photocatalytic activity for methylene blue (MB) degradation than the samples annealed under He or N2. Based on the above, this study provides new insights into the effects of annealing atmospheres and urea addition on the properties of black TiO2.
Cyperus esculentus L. and Tetracarpidium conophorum Müll. Arg. Supplemented Diet Improved Testosterone Levels, Modulated Ectonucleotidases and Adenosine Deaminase Activities in Platelets from L-NAME-Stressed Rats
Authors: Olabiyi Ayodeji Augustine , Morsch Vera Maria , Oboh Ganiyu , Schetinger Maria Rosa Chitolina
Published: October 2021

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male; 250–300 g; n = 10) were grouped into seven groups as follows: basal diet control group (I); basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II); ED-induced group (basal diet/L-NAME) (III); diet supplemented processed TN (20%)/L-NAME (IV); diet supplemented raw TN (20%)/L-NAME (V); diet supplemented processed WN (20%)/L-NAME (VI); and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2; p < 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p < 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control.
Maternal Nutrition and Neurodevelopment: A Scoping Review
Authors: Cortés-Albornoz María Camila , García-Guáqueta Danna Paola , Velez-van-Meerbeke Alberto , Talero-Gutiérrez Claudia
Published: October 2021

In this scoping review, we examined the association between maternal nutrition during pregnancy and neurodevelopment in offspring. We searched the Pubmed and ScienceDirect databases for articles published from 2000 to 2020 on inadequate intake of vitamins (B12, folate, vitamin D, vitamin A, vitamin E, vitamin K), micronutrients (cooper, iron, creatine, choline, zinc, iodine), macronutrients (fatty acids, proteins), high fat diets, ketogenic diets, hypercaloric diets, and maternal undernutrition. Some older relevant articles were included. The search produced a total of 3590 articles, and 84 studies were included in the qualitative synthesis. Data were extracted and analyzed using charts and the frequency of terms used. We concluded that inadequate nutrient intake during pregnancy was associated with brain defects (diminished cerebral volume, spina bifida, alteration of hypothalamic and hippocampal pathways), an increased risk of abnormal behavior, neuropsychiatric disorders (ASD, ADHD, schizophrenia, anxiety, depression), altered cognition, visual impairment, and motor deficits. Future studies should establish and quantify the benefits of maternal nutrition during pregnancy on neurodevelopment and recommend adequate supplementation.
Maternal Diets in India: Gaps, Barriers, and Opportunities
Authors: Nguyen Phuong Hong , Kachwaha Shivani , Tran Lan Mai , Sanghvi Tina , Ghosh Sebanti , Kulkarni Bharati , Beesabathuni Kalpana , Menon Purnima , Sethi Vani
Published: October 2021

Suboptimal dietary intake is a critical cause of poor maternal nutrition, with several adverse consequences both for mothers and for their children. This study aimed to (1) assess maternal dietary patterns in India; (2) examine enablers and barriers in adopting recommended diets; (3) review current policy and program strategies to improve dietary intakes. We used mixed methods, including empirical analysis, compiling data from available national and subnational surveys, and reviewing literature, policy, and program strategies. Diets among pregnant women are characterized by low energy, macronutrient imbalance, and inadequate micronutrient intake. Supply- and demand-side constraints to healthy diets include food unavailability, poor economic situation, low exposure to nutrition counselling, food restrictions and taboos, adverse family influence and gender norms, and gaps in knowledge. Intervention strategies with potential to improve maternal diets include food-based programs, behavior change communication, and nutrition-sensitive agriculture interventions. However, strategies face implementation bottlenecks and limited effectiveness in real-world at-scale impact evaluations. In conclusion, investments in systems approaches spanning health, nutrition, and agriculture sectors, with evaluation frameworks at subnational levels, are needed to promote healthy diets for women.
Improvement of Inflammation and Pain after Three Months’ Exclusion Diet in Rheumatoid Arthritis Patients
Authors: Guagnano Maria Teresa , D’Angelo Chiara , Caniglia Daniela , Di Giovanni Pamela , Celletti Eleonora , Sabatini Emanuela , Speranza Lorenza , Bucci Marco , Cipollone Francesco , Paganelli Roberto
Published: October 2021

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease affecting the synovial joints and causing severe disability. Environmental and lifestyle factors, including diet, have been proposed to play a role in the onset and severity of RA. Dietary manipulation may help to manage the symptoms of RA by lowering inflammation and potentially decreasing pain. Methods: In 40 patients with long-standing RA with stable symptoms and treated with conventional (c-) and biological (b-) disease modifying anti-rheumatic drugs (DMARDs), the effect of a 3-month diet avoiding meat, gluten, and lactose (and all dairy products; privative diet) was evaluated in comparison with a control balanced diet including those foods. Both diets were designed to reduce weight since all patients were overweight or obese. Patients were randomly assigned to one of the diets, and RA was clinically assessed at Time 0 (T0), through the Visual Analogue Scale (VAS), for pain, and the Disease Activity Score of 28 joints (DAS 28) for RA activity. Patients were also administered the Short Form Health survey (SF-36) and the Health Assessment Questionnaire (HAQ). At T0, a blood sample was collected for laboratory tests and adipokines measurements, and anthropometric measurements were compared. These evaluations were repeated at the end of the 3 months’ dietary regimens. Results: A significant decrease in VAS and the improvement of the overall state of physical and mental health, assessed through SF-36, was observed in patients assigned to the privative diet. Both dietary regimens resulted in the improvement of quality of life compared to baseline values; however, the change was significant only for the privative diet. With either diet, patients showed significant decreases in body weight and body mass index, with a reduction in waist and hips circumference and lower basal glucose and circulating leptin levels. A privative diet was also able to significantly reduce systolic (p = 0.003) and diastolic (p = 0.025) arterial pressure. The number of circulating leukocytes and neutrophils, and the level of hs-C-Reactive Protein also decreased after 3 months of the meat-, lactose-, and gluten-free diet. Conclusions: Our results suggest that a privative diet can result in a better control of inflammation in RA patients under stable optimized drug treatment.
Plant-Based Dietary Practices and Socioeconomic Factors That Influence Anemia in India
Authors: Bhatnagar Rohil S. , Padilla-Zakour Olga I.
Published: October 2021

While rates of malnutrition have declined over the last decade in India due to successful government interventions, the prevalence of anemia remains high. Staple foods provide almost 70% of the daily iron intake. As staple foods are a rich source of phytate, this ingested iron is poorly absorbed. Currently, 59% of children below 3 years of age, 50% of expectant mothers and 53% of women aged 15–19 years are anemic. The most common intervention strategy has been through the use of iron supplements. While the compliance has been low and supplies irregular, such high rates of anemia cannot be explained by iron deficiency alone. This review attempts to fit dietary and cooking practices, field-level diagnostics, cultural beliefs and constraints in implementation of management strategies into a larger picture scenario to offer insights as to why anemia continues to plague India. Since the rural Indian diet is predominantly vegetarian, we also review dietary factors that influence non-heme iron absorption. As a reference point, we also contrast anemia-related trends in India to the U.S.A. Thus, this review is an effort to convey a holistic evaluation while providing approaches to address this public health crisis.
DASH Diet as a Proposal for Improvement in Cellular Immunity and Its Association with Metabolic Parameters in Persons with Overweight and Obesity
Authors: Rodríguez-López Carmen Paulina , González-Torres María Cristina , Aguilar-Salinas Carlos A. , Nájera-Medina Oralia
Published: October 2021

The development of obesity entails a chronic low-grade inflammatory state with increased pro-inflammatory cells, mainly in visceral adipose tissue (VAT). Additionally, dietary patterns have an influence on the regulation of chronic inflammation. Dietary Approaches to Stop Hypertension (DASH) include foods with an anti-inflammatory profile and that have positive impacts on body composition (BC), suggesting improvements in inflammatory processes. Objective: To analyze the impact of the DASH diet on cellular immunity, anthropometric, biochemical and BC parameters in patients with overweight and obesity, who could present metabolic syndrome. Methodology: Lymphocyte subpopulations, biochemical parameters, anthropometric parameters, and BC before and 8 weeks after intervention with the DASH diet in persons with overweight and obesity were measured. Results: Fifty-nine young adults participated in the study. After the intervention, no significant changes in biochemical parameters were observed, although a significant decrease in nearly all of the anthropometric and BC variables was found: waist circumference (p < 0.001), percentage and kilograms of fat (p < 0.001 and p < 0.025, respectively), VAT (p < 0.020), and weight (p < 0.001), as well as total lymphocytes and double-positive TCD4+ cells. A relation between changes in leukocyte subpopulations (monocytes, natural killer, helper and cytotoxic lymphocytes, and naive TCD4+ cells) and metabolic improvements (glucose, triglycerides, total cholesterol and LDL-c) was also found. Conclusions: The DASH diet promotes positive changes in lymphocyte subpopulations, anthropometric parameters and BC in persons with overweight and obesity. Future studies should elucidate the cellular and molecular mechanisms through which the DASH diet produces inmunometabolic improvement.
Study of Food Intake and Physical Activity Patterns in the Working Population of the Uruguayan State Electrical Company (UTE): Design, Protocol and Methodology
Authors: Medina-Vadora Maria Mercedes , Severi Cecilia , Lecot Carlos , Ruiz-Lopez Maria Dolores , Gil Angel
Published: October 2021

Noncommunicable diseases are the main cause of death globally, and most are potentially preventable; they are long term diseases and generally evolve slowly. In Uruguay 64.9% of the population between 25 and 64 years of age are either overweight or obese. The available scientific data show that workplaces are good for developing food-intake interventions for a healthier life. The present study aims to report the design, protocol and methodology for the evaluation of the food intake and physical activity patterns of the Uruguayan State Electrical Company (UTE) workers, as it is distributed across the whole country, and has established associations with overweight and obesity in order to establish institutional strategies to improve the situation. This study uses a population and a cross-sectional, randomized, representative sample of UTE workers with a precision of 3% and a confidence level of 95%. The considered anthropometric variables are weight, height, waist circumference, percentage of fat mass and percentage of visceral fat. A questionnaire on frequency of consumption of different foods and two 24-h dietary recalls (24-h DR) will be performed to evaluate the food intake. Accelerometry will be used to evaluate physical activity, and the International physical activity questionnaire (IPAQ) will be applied. Clinical data will be obtained from the UTE clinical charts. This is the first study of its kind that will be undertaken in Uruguay. It is registered under ClinicalTrials.gov Identifier nº NCT04509908.
Assessment of the Genetic Diversity of Echinococcus multilocularis from Copro-Isolated Eggs
Authors: Knapp Jenny , Da Silva Abdou Malik , Courquet Sandra , Millon Laurence
Published: October 2021

The genetic diversity of the parasite Echinococcus multilocularis, the infectious agent of alveolar echinococcosis, is generally assessed on adult worms after fox necropsy. We aimed to investigate E. multilocularis polymorphism through the microsatellite EmsB marker using a noninvasive approach. We tested batches of isolated eggs (1, 5, and 10) from 19 carnivore fecal samples collected in a rural town located in a highly endemic area in France to determine the best strategy to adopt using a minimal quantity of parasite DNA while avoiding genetic profile overlapping in the analysis. Several molecular controls were performed to formally identify the Taeniidae eggs. In total, 112 egg batches were isolated and 102 EmsB electrophoregrams were obtained in duplicate. Quality sorting was performed through the Pearson correlation coefficient (r) between each EmsB duplicate. Forty-nine batches with r > 0.9 remained in the analysis, mainly 5- or 10-egg batches. Three EmsB profiles were emphasized by hierarchical clustering and matched those from human lesions and adult worms previously genotyped and collected in the same area. We show that the genetic diversity of the parasite can be assessed from isolated E. multilocularis eggs in a spatiotemporal context using a noninvasive approach.
Revisiting Persistent Salmonella Infection and the Carrier State: What Do We Know?
Authors: Foster Neil , Tang Ying , Berchieri Angelo , Geng Shizhong , Jiao Xinan , Barrow Paul
Published: October 2021

One characteristic of the few Salmonella enterica serovars that produce typhoid-like infections is that disease-free persistent infection can occur for months or years in a small number of individuals post-convalescence. The bacteria continue to be shed intermittently which is a key component of the epidemiology of these infections. Persistent chronic infection occurs despite high levels of circulating specific IgG. We have reviewed the information on the basis for persistence in S. Typhi, S. Dublin, S. Gallinarum, S. Pullorum, S. Abortusovis and also S. Typhimurium in mice as a model of persistence. Persistence appears to occur in macrophages in the spleen and liver with shedding either from the gall bladder and gut or the reproductive tract. The involvement of host genetic background in defining persistence is clear from studies with the mouse but less so with human and poultry infections. There is increasing evidence that the organisms (i) modulate the host response away from the typical Th1-type response normally associated with immune clearance of an acute infection to Th2-type or an anti-inflammatory response, and that (ii) the bacteria modulate transformation of macrophage from M1 to M2 type. The bacterial factors involved in this are not yet fully understood. There are early indications that it might be possible to remodulate the response back towards a Th1 response by using cytokine therapy.
Effects of Local and Systemic Immune Challenges on the Expression of Selected Salivary Genes in the Malaria Mosquito Anopheles coluzzii
Authors: Bevivino Giulia , Arcà Bruno , Lombardo Fabrizio
Published: October 2021

Salivary glands play a crucial tripartite role in mosquito physiology. First, they secrete factors that greatly facilitate both sugar and blood meal acquisition. Second, the transmission of pathogens (parasites, bacteria and viruses) to the vertebrate host requires both the recognition and invasion of the salivary glands. Third, they produce immune factors that both protect the organ from invading pathogens and are also able to exert their activity in the crop and the midgut when saliva is re-ingested during feeding. Studies on mosquito sialomes have revealed the presence of several female and/or male salivary gland-specific or enriched genes whose function is completely unknown so far. We focused our attention on these orphan genes, and we selected, according to sequence and structural features, a shortlist of 11 candidates with potential antimicrobial properties. Afterwards, using qPCR, we investigated their expression profile at 5 and 24 h after an infectious sugar meal (local challenge) or thoracic microinjection (systemic challenge) of Gram-negative (Escherichia coli, EC) or Gram-positive (Staphylococcus aureus, SA) bacteria. We observed a general increase in the transcript abundance of our salivary candidates between 5 and 24 h after local challenge. Moreover, transcriptional modulation was determined by the nature of the stimulus, with salivary gland-enriched genes (especially hyp15 upon SA stimulus) upregulated shortly after the local challenge and later after the systemic challenge. Overall, this work provides one of the first contributions to the understanding of the immune role of mosquito salivary glands. Further characterization of salivary candidates whose expression is modulated by immune challenge may help in the identification of possible novel antimicrobial peptides.
Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
Authors: Nair Sreeja C. , Vinayan Kollencheri Puthenveettil , Mangalathillam Sabitha
Published: October 2021

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.
Tumor-Targeted ZW800-1 Analog for Enhanced Tumor Imaging and Photothermal Therapy
Authors: Park Min-Ho , Jo Gayoung , Kim Eun-Jeong , Hyun Hoon
Published: October 2021

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.
CRISPR/Cas9 Delivery System Engineering for Genome Editing in Therapeutic Applications
Authors: Cheng Hao , Zhang Feng , Ding Yang
Published: October 2021

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) systems have emerged as a robust and versatile genome editing platform for gene correction, transcriptional regulation, disease modeling, and nucleic acids imaging. However, the insufficient transfection and off-target risks have seriously hampered the potential biomedical applications of CRISPR/Cas9 technology. Herein, we review the recent progress towards CRISPR/Cas9 system delivery based on viral and non-viral vectors. We summarize the CRISPR/Cas9-inspired clinical trials and analyze the CRISPR/Cas9 delivery technology applied in the trials. The rational-designed non-viral vectors for delivering three typical forms of CRISPR/Cas9 system, including plasmid DNA (pDNA), mRNA, and ribonucleoprotein (RNP, Cas9 protein complexed with gRNA) were highlighted in this review. The vector-derived strategies to tackle the off-target concerns were further discussed. Moreover, we consider the challenges and prospects to realize the clinical potential of CRISPR/Cas9-based genome editing.
DABCO-Customized Nanoemulsions: Characterization, Cell Viability and Genotoxicity in Retinal Pigmented Epithelium and Microglia Cells
Authors: Fernandes Ana R. , Santos Tiago dos , Granja Pedro L. , Sanchez-Lopez Elena , Santini Antonello , Garcia Maria L. , Silva Amelia M. , Souto Eliana B.
Published: October 2021

Quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and of quinuclidine surfactants were used to develop oil-in-water nanoemulsions with the purpose of selecting the best long-term stable nanoemulsion for the ocular administration of triamcinolone acetonide (TA). The combination of the best physicochemical properties (i.e., mean droplet size, polydispersity index, zeta potential, osmolality, viscoelastic properties, surface tension) was considered, together with the cell viability assays in ARPE-19 and HMC3 cell lines. Surfactants with cationic properties have been used to tailor the nanoemulsions’ surface for site-specific delivery of drugs to the ocular structure for the delivery of TA. They are tailored for the eye because they have cationic properties that interact with the anionic surface of the eye.
The Novel Cucurbitaceae miRNA ClmiR86 Is Involved in Grafting-Enhanced Phosphate Utilization and Phosphate Starvation Tolerance in Watermelon
Authors: Wu Weifang , Zhao Haoshun , Deng Qin , Yang Haiyang , Guan Xiaoxiao , Qi Rui , Shi Pibiao , Yang Jinghua , Zhang Mingfang , Hu Zhongyuan
Published: October 2021

Watermelon (Citrullus lanatus) is a globally important Cucurbitaceae crop in which grafting is commonly used to improve stress tolerance and enhance nutrient utilization. However, the mechanism underlying grafting-enhanced nutrient assimilation remains unclear. Here, we demonstrate the possible involvement of a novel Cucurbitaceae miRNA, ClmiR86, in grafting-enhanced phosphate-starvation tolerance via CALCINEURIN B-LIKE INTERACTING PROTEIN KINASE 5 (ClCIPK5) suppression in watermelon. Transcript analyses revealed that the induction of ClmiR86 expression was correlated with the downregulation of ClCIPK5 in squash-grafted watermelon under phosphate starvation. In addition, the differential expression of ClmiR86 in various watermelon genotypes was consistent with their phosphate utilization efficiency. Furthermore, ClmiR86 overexpression in Arabidopsis enhanced root growth and phosphate uptake under phosphate starvation and promoted inflorescence elongation under normal conditions. These results suggest that the ClmiR86–ClCIPK5 axis is involved in phosphate starvation response as well as grafting-enhanced growth vigor and phosphate assimilation. The present study provides valuable insights for investigating long-distance signaling and nutrient utilization in plants.
Physicochemical Characteristics and Bioactive Compounds of New Black Cherry Tomato (Solanum lycopersicum) Varieties Grown in Vietnam
Authors: Ha Ho Thi Ngan , Van Tai Ngo , Thuy Nguyen Minh
Published: October 2021

Some physicochemical characteristics and bioactive compounds of three varieties of black cherry tomato (Indigo Rose, OG, F1:001) grown in Vietnam were investigated. The results showed that the two varieties OG and F1:001 have roughly the same size with weight, height, diameter, geometric diameter and surface area ranging from 21.62 to 22.25 g, 25.69 to 26.40 mm, 24.46 to 25.11 mm, 24.86 to 25.53 mm and 19.47 to 20.51 cm2, respectively. Meanwhile, the Indigo variety is twice as large with the corresponding parameters as 45.2 g, 48.03 mm, 55.18 mm, 52.69 mm and 87.20 cm2. All three varieties are in a spherical shape with sphericity and aspect ratios ranging from 96.72 to 109.69% and 0.951 to 1.149, respectively. The variety of OG contained higher levels of bioactive compounds, especially anthocyanin, not only in the skin but also in the outer tissue. Six anthocyanin compounds were identified in the two varieties of OG and Indigo Rose while only four anthocyanin compounds were found in the variety of F1:001. Among them, two new compounds (delphinidin-3-(p-coumaroyl)-glucoside and delphinidin-3-(p-coumaroyl)-glucoside-arabinoside) were discovered in all three varieties. The finding of this study will be a basis for consumers to better understand the nutritious properties of black cherry tomatoes grown in Vietnam, thereby promoting the need to grow and consume this beneficial fruit. The study also provides the important physicochemical parameters of black cherry tomatoes, which are the initial basis for fruit preservation and processing.
Membrane Trafficking Proteins: A New Target to Identify Resistance to Viruses in Plants
Authors: Agaoua Aimeric , Bendahmane Abdelhafid , Moquet Frédéric , Dogimont Catherine
Published: October 2021

Replication cycles from most simple-stranded positive RNA viruses infecting plants involve endomembrane deformations. Recent published data revealed several interactions between viral proteins and plant proteins associated with vesicle formation and movement. These plant proteins belong to the COPI/II, SNARE, clathrin and ESCRT endomembrane trafficking mechanisms. In a few cases, variations of these plant proteins leading to virus resistance have been identified. In this review, we summarize all known interactions between these plant cell mechanisms and viruses and highlight strategies allowing fast identification of variant alleles for membrane-associated proteins.