bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection
Authors: Vogel-González Marina , Talló-Parra Marc , Herrera-Fernández Víctor , Pérez-Vilaró Gemma , Chillón Miguel , Nogués Xavier , Gómez-Zorrilla Silvia , López-Montesinos Inmaculada , Arnau-Barrés Isabel , Sorli-Redó Maria Luisa , Horcajada Juan Pablo , García-Giralt Natalia , Pascual Julio , Díez Juana , Vicente Rubén , Güerri-Fernández Robert
Published: February 2021

Background: Zinc is an essential micronutrient that impacts host–pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. Methods: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. Findings: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. Interpretation: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.
Edible Microalgae and Their Bioactive Compounds in the Prevention and Treatment of Metabolic Alterations
Authors: Ramos-Romero Sara , Torrella Joan Ramon , Pagès Teresa , Viscor Ginés , Torres Josep Lluís
Published: February 2021

Marine and freshwater algae and their products are in growing demand worldwide because of their nutritional and functional properties. Microalgae (unicellular algae) will constitute one of the major foods of the future for nutritional and environmental reasons. They are sources of high-quality protein and bioactive molecules with potential application in the modern epidemics of obesity and diabetes. They may also contribute decisively to sustainability through carbon dioxide fixation and minimization of agricultural land use. This paper reviews current knowledge of the effects of consuming edible microalgae on the metabolic alterations known as metabolic syndrome (MS). These microalgae include Chlorella, Spirulina (Arthrospira) and Tetraselmis as well as Isochrysis and Nannochloropsis as candidates for human consumption. Chlorella biomass has shown antioxidant, antidiabetic, immunomodulatory, antihypertensive, and antihyperlipidemic effects in humans and other mammals. The components of microalgae reviewed suggest that they may be effective against MS at two levels: in the early stages, to work against the development of insulin resistance (IR), and later, when pancreatic -cell function is already compromised. The active components at both stages are antioxidant scavengers and anti-inflammatory lipid mediators such as carotenoids and -3 PUFAs (eicosapentaenoic acid/docosahexaenoic acid; EPA/DHA), prebiotic polysaccharides, phenolics, antihypertensive peptides, several pigments such as phycobilins and phycocyanin, and some vitamins, such as folate. As a source of high-quality protein, including an array of bioactive molecules with potential activity against the modern epidemics of obesity and diabetes, microalgae are proposed as excellent foods for the future. Moreover, their incorporation into the human diet would decisively contribute to a more sustainable world because of their roles in carbon dioxide fixation and reducing the use of land for agricultural purposes.
A Priori and a Posteriori Dietary Patterns among Pregnant Women in Johannesburg, South Africa: The NuPED Study
Authors: Conradie Cornelia , Baumgartner Jeannine , Malan Linda , Symington Elizabeth A. , Cockeran Marike , Smuts Cornelius M. , Faber Mieke
Published: February 2021

Dietary pattern analyses allow assessment of the diet as a whole. Limited studies include both a priori and a posteriori dietary pattern analyses. This study aimed to explore the diet of pregnant women in urban South Africa through both a priori and a posteriori dietary pattern analyses and associated maternal and household factors. Dietary data were collected during early pregnancy using a quantified food frequency questionnaire from 250 pregnant women enrolled in the Nutrition During Pregnancy and Early Development (NuPED) cohort. A priori dietary patterns were determined using the Diet Quality Index-International (DQI-I), and a posteriori nutrient patterns using exploratory factor analysis. Based on the DQI-I, the study population followed a borderline low-quality diet. Three a posteriori nutrient patterns were identified: Pattern 1 “plant protein, iron, thiamine, and folic acid”; pattern 2 “animal protein, copper, vitamin A, and vitamin B12”; pattern 3 “fatty acids and sodium”. Pattern 1 was associated with higher dietary quality (p < 0.001), lower maternal educational level (p = 0.03) and socioeconomic status (p < 0.001). Pattern 3 was significantly associated with lower dietary quality. The low dietary quality among pregnant women residing in urban South Africa should be addressed to ensure optimal maternal and offspring health outcomes.
Physical Education and the Adoption of Habits Related to the Mediterranean Diet
Authors: Lirola María-Jesús , Trigueros Rubén , Aguilar-Parra Jose M. , Mercader Isabel , Fernandez Campoy Juan M. , del Pilar Díaz-López Mª
Published: February 2021

Childhood obesity and sedentary lifestyles are now gaining a foothold in the Western world. The aim of this research was to analyse the influence of physical education classes on a healthy diet (i.e., Mediterranean diet). To this end, psychological constructs derived from the theory of self-determination and the theory of planned behaviour were taken into account, such as the satisfaction and frustration of basic psychological needs, motivation in physical education classes, and social cognition and intention. A total of 3415 secondary school students (13–19 years) participated in this study. A structural equation model was proposed that would explain the relationships between the variables mentioned above and the adherence to a Mediterranean diet. The results provide adequate fit indexes for the proposed model. Based on the results of the study, it was concluded that a high satisfaction perceived in the physical education classes would help to reinforce the intention of having a healthy diet and therefore help to generate a perdurable commitment to this habit.
Gluten and Autism Spectrum Disorder
Authors: Croall Iain D. , Hoggard Nigel , Hadjivassiliou Marios
Published: February 2021

An expanding body of literature is examining connections between Autism Spectrum Disorder (ASD) and dietary interventions. While a number of specialist diets have been suggested as beneficial in ASD, gluten has received particularly close attention as a potentially exacerbating factor. Reports exist suggesting a beneficial effect of the gluten-free diet (GFD) in ameliorating behavioural and intellectual problems associated with ASD, while epidemiological research has also shown a comorbidity between ASD and coeliac disease. However, both caregivers and clinicians have expressed an uncertainty of the value of people with ASD going gluten-free, and as the GFD otherwise receives considerable public attention a discussion which focuses specifically on the interaction between ASD and gluten is warranted. In this review we discuss the historical context of ASD and gluten-related studies, and expand this to include an overview of epidemiological links, hypotheses of shared pathological mechanisms, and ultimately the evidence around the use and adoption of the GFD in people with ASD.
Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study
Authors: Monthé-Drèze Carmen , Sen Sarbattama , Hauguel-de Mouzon Sylvie , Catalano Patrick M.
Published: February 2021

Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored. We conducted a pilot double-blind randomized controlled trial of 72 pregnant women with first trimester body mass index (BMI) ≥ 25 kg/m2 to explore preliminary efficacy of n-3 supplementation. Participants were randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10–16 weeks gestation to delivery. Neonatal body composition, fetal growth and length of gestation were assessed. For the 48 dyads with outcome data, median (IQR) maternal BMI was 30.2 (28.2, 35.4) kg/m2. In sex-adjusted analyses, n-3 supplementation was associated with higher neonatal fat-free mass (β: 218 g; 95% CI 49, 387) but not with % body fat or fat mass. Birthweight for gestational age z-score (−0.17 ± 0.67 vs. −0.61 ± 0.61 SD unit, p = 0.02) was higher, and gestation longer (40 (38.5, 40.1) vs. 39 (38, 39.4) weeks, p = 0.02), in the treatment vs. placebo group. Supplementation with n-3 PUFA in women with OWOB led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. Larger well-powered trials of n-3 PUFA supplementation specifically in pregnant women with OWOB should be conducted to confirm these findings and explore the long-term impact on offspring obesity and cardiometabolic health.
Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects
Authors: Larson Riley , Nelson Courtney , Korczak Renee , Willis Holly , Erickson Jennifer , Wang Qi , Slavin Joanne
Published: February 2021

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.
African Swine Fever Laboratory Diagnosis—Lessons Learned from Recent Animal Trials
Authors: Pikalo Jutta , Deutschmann Paul , Fischer Melina , Roszyk Hanna , Beer Martin , Blome Sandra
Published: February 2021

African swine fever virus (ASFV) causes a hemorrhagic disease in pigs with high socio-economic consequences. To lower the impact of disease incursions, early detection is crucial. In the context of experimental animal trials, we evaluated diagnostic workflows for a high sample throughput in active surveillance, alternative sample matrices for passive surveillance, and lateral flow devices (LFD) for rapid testing. We could demonstrate that EDTA blood is significantly better suited for early ASFV detection than serum. Tissues recommended by the respective diagnostic manuals were in general comparable in their performance, with spleen samples giving best results. Superficial lymph nodes, ear punches, and different blood swabs were also evaluated as potential alternatives. In summary, all matrices yielded positive results at the peak of clinical signs and could be fit for purpose in passive surveillance. However, weaknesses were discovered for some matrices when it comes to the early phase of infection or recovery. The antigen LFD showed variable results with best performance in the clinical phase. The antibody LFD was quite comparable with ELISA systems. Concluding, alternative approaches are feasible but have to be embedded in control strategies selecting test methods and sample materials following a “fit-for-purpose” approach.
Occurrence and Multi-Locus Analysis of Giardia duodenalis in Coypus (Myocastor coypus) in China
Authors: Cui Zhaohui , Wang Deguo , Wang Wen , Zhang Ying , Jing Bo , Xu Chunyan , Chen Yuanchai , Qi Meng , Zhang Longxian
Published: February 2021

Giardia duodenalis is a major gastrointestinal parasite found globally in both humans and animals. This work examined the occurrence of G. duodenalis in coypus (Myocastor coypus) in China. Multi-locus analysis was conducted to evaluate the level of genetic variation and the potential zoonotic role of the isolates. In total, 308 fecal samples were collected from seven farms in China and subjected to PCR screening to reveal G. duodenalis. Notably, G. duodenalis was detected in 38 (12.3%) specimens from assemblages A (n = 2) and B (n = 36). Positive samples were further characterized by PCR and nucleotide sequencing of the triose phosphate isomerase (tpi), beta giardin (bg), and glutamate dehydrogenase (gdh) genes. Multi-locus genotyping yielded 10 novel multi-locus genotypes (MLGs) (one MLG and nine MLGs for assemblages A and B, respectively). Based on the generated phylogenetic tree, AI–novel 1 clustered more closely with MLG AI-2. Furthermore, within the assemblage B phylogenetic analysis, the novel assemblage B MLGs were identified as BIV and clustered in the MLG BIV branch. This is the first report of G. duodenalis in coypus in China. The presence of zoonotic genotypes and subtypes of G. duodenalis in coypus suggests that these animals can transmit human giardiasis.
Comparison of UV, Peracetic Acid and Sodium Hypochlorite Treatment in the Disinfection of Urban Wastewater
Authors: Bonetta Silvia , Pignata Cristina , Bonetta Sara , Amagliani Giulia , Brandi Giorgio , Gilli Giorgio , Carraro Elisabetta
Published: February 2021

One source of water contamination is the release of wastewater that has not undergone efficient treatment. The aim of this study was to evaluate the reduction obtained with sodium hypochlorite (NaClO), UV and peracetic acid disinfection treatment of Salmonella spp., pathogenic Campylobacter, STEC and bacterial indicators in three full-scale municipal wastewater plants. A general reduction in Salmonella was observed after disinfection, but these bacteria were detected in one UV-treated sample (culture method) and in 33%, 50% and 17% of samples collected after NaClO, UV and PAA disinfection treatments, respectively (PCR method). A better reduction was also observed under NaClO disinfection for the microbial indicators. Independent of the disinfection treatment, E. coli O157:H7 was not detected in the disinfected samples, whereas some samples treated with UV and PAA showed the presence of the stx1 gene. No reduction in the presence of stx2 genes was verified for any of the disinfection treatments. Campylobacter was not detected in any of the analysed samples. The overall results highlight a better reduction in microbiological parameters with a NaClO disinfection treatment in a full-scale municipal wastewater plant compared with UV and PAA. However, the results indicate that a complete and specific monitoring program is necessary to prevent a possible risk to public health.
Differing Effects of Standard and Harsh Nucleic Acid Extraction Procedures on Diagnostic Helminth Real-Time PCRs Applied to Human Stool Samples
Authors: Hoffmann Tanja , Hahn Andreas , Verweij Jaco J. , Leboulle Gérard , Landt Olfert , Strube Christina , Kann Simone , Dekker Denise , May Jürgen , Frickmann Hagen , Loderstädt Ulrike
Published: February 2021

This study aimed to assess standard and harsher nucleic acid extraction schemes for diagnostic helminth real-time PCR approaches from stool samples. A standard procedure for nucleic acid extraction from stool and a procedure including bead-beating as well as proteinase K digestion were compared with group-, genus-, and species-specific real-time PCR assays targeting helminths and nonhelminth pathogens in human stool samples. From 25 different in-house and commercial helminth real-time PCR assays applied to 77 stool samples comprising 67 historic samples and 10 external quality assessment scheme samples positively tested for helminths, higher numbers of positive test results were observed after bead-beating-based nucleic acid extraction for 5/25 (20%) real-time PCR assays irrespective of specificity issues. Lower cycle threshold values were observed for one real-time PCR assay after the standard extraction scheme, and for four assays after the bead-beating-based scheme. Agreement between real-time PCR results after both nucleic acid extraction strategies according to Cohen’s kappa ranged from poor to almost perfect for the different assays. Varying agreement was observed in eight nonhelminth real-time PCR assays applied to 67 historic stool samples. The study indicates highly variable effects of harsh nucleic acid extraction approaches depending on the real-time PCR assay used.
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
Authors: Gabriel Iwona , Rząd Kamila , Paluszkiewicz Ewa , Kozłowska-Tylingo Katarzyna
Published: February 2021

In the last few years, increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds which are highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and other adverse effects. In addition, the frequent use of available fungistatic drugs promotes drug resistance. Therefore, there is an urgent need for the development of a novel antifungal drug with a different mechanism of action, blocking of the fungal DNA topoisomerases activity appear to be a promising idea. According to previous studies on the m-AMSA moderate inhibitory effect on fungal topoisomerase II, we have decided to study Capridine β (also acridine derivative) antifungal activity, as well as its inhibitory potential on yeast topoisomerase II (yTOPOII). Results indicated that Capridine β antifungal activity depends on the kind of strains analyzed (MICs range 0.5–64 μg mL−1) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus Candida albicans was performed. IE1 exhibited no activity against fungal cells due to an inability to enter the cells. Although no antifungal activity was observed, in contrast to Capridine β, biotransformation metabolite totally inhibited the yTOPOII-mediated relaxation at concentrations lower than detected for m-AMSA. The closely related Capridine β only slightly diminished the catalytic activity of yTOPOII.
Toxocara cati and Other Parasitic Enteropathogens: More Commonly Found in Owned Cats with Gastrointestinal Signs Than in Clinically Healthy Ones
Authors: Ursache Aurora L. , Györke Adriana , Mircean Viorica , Dumitrache Mirabela O. , Codea Andrei Răzvan , Cozma Vasile
Published: February 2021

Intestinal parasites are involved in the health and wellbeing of cats and some of them, due to their zoonotic potential, represent a problem for public health. This study aimed to assess the prevalence of parasitic infections in cats with gastrointestinal signs. Fecal samples collected from 137 cats were analyzed by the flotation method using a sodium chloride saturated solution. The overall prevalence of intestinal parasites was 50.4%. Intestinal parasites were significantly (p < 0.0001) more common in cats with digestive clinical signs (66.7%) than in clinically healthy ones (19.2%). Toxocara cati (40.2%) was the most frequently identified intestinal parasite, followed by Cystoisospora spp. (10.2%), hookworms (3.7%), Taeniidae (2.2%), Giardia duodenalis (2.2%), and Toxoplasma gondii (0.7%). Toxocara cati (53.3%, p < 0.0001) and Cystoisospora spp. (15.6%, p < 0.001) were significantly more frequently diagnosed in cats with clinical signs. A lack of deworming in the last three months (OR: 15.9), outdoor access (OR: 13.8), the presence of digestive symptoms (OR: 5.4), and young age (OR: 4.2) were identified as risk factors for T. cati infection by logistic regression analysis. Regardless of age, gastrointestinal signs like vomiting, diarrhea, and inappetence were positively associated with T. cati.
Regulation of Latency and Reactivation by Human Cytomegalovirus miRNAs
Authors: Diggins Nicole L. , Skalsky Rebecca L. , Hancock Meaghan H.
Published: February 2021

Human cytomegalovirus (HCMV) encodes 22 mature microRNAs (miRNAs), which regulate a myriad of cellular processes, including vesicular trafficking, cell cycle progression, apoptosis, and immune evasion, as well as viral gene expression. Recent evidence points to a critical role for HCMV miRNAs in mediating latency in CD34+ hematopoietic progenitor cells through modulation of cellular signaling pathways, including attenuation of TGFβ and EGFR signaling. Moreover, HCMV miRNAs can act in concert with, or in opposition to, viral proteins in regulating host cell functions. Here, we comprehensively review the studies of HCMV miRNAs in the context of latency and highlight the novel processes that are manipulated by the virus using these small non-coding RNAs.
Genomic and Phenotypic Analysis of Multidrug-Resistant Acinetobacter baumannii Clinical Isolates Carrying Different Types of CRISPR/Cas Systems
Authors: Tyumentseva Marina , Mikhaylova Yulia , Prelovskaya Anna , Tyumentsev Aleksandr , Petrova Lyudmila , Fomina Valeria , Zamyatin Mikhail , Shelenkov Andrey , Akimkin Vasiliy
Published: February 2021

Acinetobacter baumannii is an opportunistic pathogen being one of the most important causative agents of a wide range of nosocomial infections associated with multidrug resistance and high mortality rate. This study presents a multiparametric and correlation analyses of clinical multidrug-resistant A. baumannii isolates using short- and long-read whole-genome sequencing, which allowed us to reveal specific characteristics of the isolates with different CRISPR/Cas systems. We also compared antibiotic resistance and virulence gene acquisition for the groups of the isolates having functional CRISPR/Cas systems, just CRISPR arrays without cas genes, and without detectable CRISPR spacers. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as phylogenetic analysis of full-length cas gene sequences, predicted prophage sequences and CRISPR array type determination. For the first time the differences between the isolates carrying Type I-F1 and Type I-F2 CRISPR/Cas systems were investigated. A. baumannii isolates with Type I-F1 system were shown to have smaller number of reliably detected CRISPR arrays, and thus they could more easily adapt to environmental conditions through acquisition of antibiotic resistance genes, while Type I-F2 A. baumannii might have stronger “immunity” and use CRISPR/Cas system to block the dissemination of these genes. In addition, virulence factors abaI, abaR, bap and bauA were overrepresented in A. baumannii isolates lacking CRISPR/Cas system. This indicates the role of CRISPR/Cas in fighting against phage infections and preventing horizontal gene transfer. We believe that the data presented will contribute to further investigations in the field of antimicrobial resistance and CRISPR/Cas studies.
Monofunctional Platinum(II) Anticancer Agents
Authors: Jin Suxing , Guo Yan , Guo Zijian , Wang Xiaoyong
Published: February 2021

Platinum-based anticancer drugs represented by cisplatin play important roles in the treatment of various solid tumors. However, their applications are largely compromised by drug resistance and side effects. Much effort has been made to circumvent the drug resistance and general toxicity of these drugs. Among multifarious designs, monofunctional platinum(II) complexes with a general formula of [Pt(3A)Cl]+ (A: Ammonia or amine) stand out as a class of “non-traditional” anticancer agents hopeful to overcome the defects of current platinum drugs. This review aims to summarize the development of monofunctional platinum(II) complexes in recent years. They are classified into four categories: fluorescent complexes, photoactive complexes, targeted complexes, and miscellaneous complexes. The intention behind the designs is either to visualize the cellular distribution, or to reduce the side effects, or to improve the tumor selectivity, or inhibit the cancer cells through non-DNA targets. The information provided by this review may inspire researchers to conceive more innovative complexes with potent efficacy to shake off the drawbacks of platinum anticancer drugs.
Ameliorative Effects of Loganin on Arthritis in Chondrocytes and Destabilization of the Medial Meniscus-Induced Animal Model
Authors: Park Eunkuk , Lee Chang Gun , Yun Seung Hee , Hwang Seokjin , Jeon Hyoju , Kim Jeonghyun , Yeo Subin , Jeong Hyesoo , Yun Seong-Hoon , Jeong Seon-Yong
Published: February 2021

Arthritis is a common inflammatory disease that causes pain, stiffness, and joint swelling. Here, we investigated the ameliorative effects of loganin on arthritis in vitro and in vivo. A single bioactive compound was fractionated and isolated from Cornus officinalis (CO) extract to screen for anti-arthritic effects. A single component, loganin, was identified as a candidate. The CO extract and loganin inhibited the expression of factors associated with cartilage degradation, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMP-3), and matrix metalloproteinase 13 (MMP-13), in interukin-1 beta (IL-1β)-induced chondrocyte inflammation. In addition, prostaglandin and collagenase levels were reduced following treatment of IL-1β-induced chondrocytes with loganin. In the destabilization of the medial meniscus (DMM)-induced mouse model, loganin administration attenuated cartilage degeneration by inhibiting COX-2, MMP-3, and MMP-13. Transverse micro-CT images revealed that loganin reduced DMM-induced osteophyte formation. These results indicate that loganin has protective effects in DMM-induced mice.
MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer
Authors: Jung Eunsun , Choi Jinhyeon , Kim Jang-Seong , Han Tae-Su
Published: February 2021

Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.
miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis
Authors: Papagiannopoulos Christos I. , Theodoroula Nikoleta F. , Vizirianakis Ioannis S.
Published: February 2021

miRNAs constitute a class of non-coding RNA that act as powerful epigenetic regulators in animal and plant cells. In order to identify putative tumor-suppressor miRNAs we profiled the expression of various miRNAs during differentiation of erythroleukemia cells. RNA was purified before and after differentiation induction and subjected to quantitative RT-PCR. The majority of the miRNAs tested were found upregulated in differentiated cells with miR-16-5p showing the most significant increase. Functional studies using gain- and loss-of-function constructs proposed that miR-16-5p has a role in promoting the erythroid differentiation program of murine erythroleukemia (MEL) cells. In order to identify the underlying mechanism of action, we utilized bioinformatic in-silico platforms that incorporate predictions for the genes targeted by miR-16-5p. Interestingly, ribosome constituents, as well as ribosome biogenesis factors, were overrepresented among the miR-16-5p predicted gene targets. Accordingly, biochemical experiments showed that, indeed, miR-16-5p could modulate the levels of independent ribosomal proteins, and the overall ribosomal levels in cultured cells. In conclusion, miR-16-5p is identified as a differentiation-promoting agent in erythroleukemia cells, demonstrating antiproliferative activity, likely as a result of its ability to target the ribosomal machinery and restore any imbalanced activity imposed by the malignancy and the blockade of differentiation.
Photophysical Properties of Protoporphyrin IX, Pyropheophorbide-a, and Photofrin® in Different Conditions
Authors: Myrzakhmetov Bauyrzhan , Arnoux Philippe , Mordon Serge , Acherar Samir , Tsoy Irina , Frochot Céline
Published: February 2021

Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or decrease in fluorescence emission and formation of reactive oxygen species (ROS) especially singlet oxygen (1O2). In this study, the influence of solvent polarity, viscosity, concentration, temperature, and pH medium on the photophysical properties of protoporphyrin IX, pyropheophorbide-a, and Photofrin® were investigated by UV-visible absorption, fluorescence emission, singlet oxygen emission, and time-resolved fluorescence spectroscopies.
Biofabricated Fatty Acids-Capped Silver Nanoparticles as Potential Antibacterial, Antifungal, Antibiofilm and Anticancer Agents
Authors: Ansari Mohammad Azam , Asiri Sarah Mousa Maadi , Alzohairy Mohammad A. , Alomary Mohammad N. , Almatroudi Ahmad , Khan Firdos Alam
Published: February 2021

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.
Pharyngeal Pumping and Tissue-Specific Transgenic P-Glycoprotein Expression Influence Macrocyclic Lactone Susceptibility in Caenorhabditis elegans
Authors: Gerhard Alexander P. , Krücken Jürgen , Neveu Cedric , Charvet Claude L. , Harmache Abdallah , von Samson-Himmelstjerna Georg
Published: February 2021

Macrocyclic lactones (MLs) are widely used drugs to treat and prevent parasitic nematode infections. In many nematode species including a major pathogen of foals, Parascaris univalens, resistance against MLs is widespread, but the underlying resistance mechanisms and ML penetration routes into nematodes remain unknown. Here, we examined how the P-glycoprotein efflux pumps, candidate genes for ML resistance, can modulate drug susceptibility and investigated the role of active drug ingestion for ML susceptibility in the model nematode Caenorhabditis elegans. Wildtype or transgenic worms, modified to overexpress P. univalens PGP-9 (Pun-PGP-9) at the intestine or epidermis, were incubated with ivermectin or moxidectin in the presence (bacteria or serotonin) or absence (no specific stimulus) of pharyngeal pumping (PP). Active drug ingestion by PP was identified as an important factor for ivermectin susceptibility, while moxidectin susceptibility was only moderately affected. Intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation. Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP and against ivermectin only in the absence of active drug ingestion. Our results demonstrate the role of active drug ingestion by nematodes for susceptibility and provide functional evidence for the contribution of P-glycoproteins to ML resistance in a tissue-specific manner.
The Treatment of Lung Involvement in Systemic Sclerosis
Authors: Ruaro Barbara , Confalonieri Marco , Matucci-Cerinic Marco , Salton Francesco , Confalonieri Paola , Santagiuliana Mario , Citton Gloria Maria , Baratella Elisa , Bruni Cosimo
Published: February 2021

Systemic sclerosis (SSc) patients are often affected by interstitial lung disease (ILD) and, although there have been recent treatment advances, it remains the leading cause of death among SSc, with a 10-year mortality up to 40%. African Americans and subjects with diffuse cutaneous SSc or anti-topoisomerase 1 antibodies are most commonly affected. Currently, early ILD diagnosis can be made, and it is pivotal to improve the prognosis. The diagnostic mainstay test for SSc-ILD is high-resolution computed tomography for the morphology and pulmonary function tests for the functional aspects. Treatment planning and intensity are guided by the disease severity and risk of progression. Traditionally, therapy has depended on combinations of immunosuppressants, particularly cyclophosphamide and mycophenolate mofetil, which can be supplemented by targeted biological and antifibrotic therapies. Benefits have been observed in trials on hematopoietic autologous stem cell transplantation for patients with progressive SSc, whilst lung transplantation is reserved for refractory SSc-ILD cases. Herein, recent advances in SSc-ILD treatment will be explored.
Novel Green Biosynthesis of 5-Fluorouracil Chromium Nanoparticles Using Harpullia pendula Extract for Treatment of Colorectal Cancer
Authors: Saddik Mohammed S. , Elsayed Mahmoud M. A. , Abdelkader Mohamed Salaheldin A. , El-Mokhtar Mohamed A. , Abdel-Aleem Jelan A. , Abu-Dief Ahmed M. , Al-Hakkani Mostafa F. , Farghaly Hatem S. , Abou-Taleb Heba A.
Published: February 2021

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box–Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.
Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin
Authors: Silva Filippo , Sitia Leopoldo , Allevi Raffaele , Bonizzi Arianna , Sevieri Marta , Morasso Carlo , Truffi Marta , Corsi Fabio , Mazzucchelli Serena
Published: February 2021

Protein nanocages represent an emerging candidate among nanoscaled delivery systems. Indeed, they display unique features that proved to be very interesting from the nanotechnological point of view such as uniform structure, stability in biological fluids, suitability for surface modification to insert targeting moieties and loading with different drugs and dyes. However, one of the main concerns regards the production as recombinant proteins in E. coli, which leads to a product with high endotoxin contamination, resulting in nanocage immunogenicity and pyrogenicity. Indeed, a main challenge in the development of protein-based nanoparticles is finding effective procedures to remove endotoxins without affecting protein stability, since every intravenous injectable formulation that should be assessed in preclinical and clinical phase studies should display endotoxins concentration below the admitted limit of 5 EU/kg. Different strategies could be employed to achieve such a result, either by using affinity chromatography or detergents. However, these strategies are not applicable to protein nanocages as such and require implementations. Here we propose a combined protocol to remove bacterial endotoxins from nanocages of human H-ferritin, which is one of the most studied and most promising protein-based drug delivery systems. This protocol couples the affinity purification with the Endotrap HD resin to a treatment with Triton X-114. Exploiting this protocol, we were able to obtain excellent levels of purity maintaining good protein recovery rates, without affecting nanocage interactions with target cells. Indeed, binding assay and confocal microscopy experiments confirm that purified H-ferritin retains its capability to specifically recognize cancer cells. This procedure allowed to obtain injectable formulations, which is preliminary to move to a clinical trial.
Are Nutraceuticals Beneficial in Chronic Kidney Disease?
Authors: Rysz Jacek , Franczyk Beata , Kujawski Krzysztof , Sacewicz-Hofman Izabela , Ciałkowska-Rysz Aleksanda , Gluba-Brzózka Anna
Published: February 2021

Chronic kidney disease (CKD) is a worldwide health problem in which prevalence is constantly rising. The pathophysiology of CKD is complicated and has not been fully resolved. However, elevated oxidative stress is considered to play a vital role in the development of this disease. CKD is also thought to be an inflammatory disorder in which uremic toxins participate in the development of the inflammatory milieu. A healthy, balanced diet supports the maintenance of a good health status as it helps to reduce the risk of the development of chronic diseases, including chronic kidney disease, diabetes mellitus, and hypertension. Numerous studies have demonstrated that functional molecules and nutrients, including fatty acids and fiber as well as nutraceuticals such as curcumin, steviol glycosides, and resveratrol not only exert beneficial effects on pro-inflammatory and anti-inflammatory pathways but also on gut mucosa. Nutraceuticals have attracted great interest recently due to their potential favorable physiological effects on the human body and their safety. This review presents some nutraceuticals in which consumption could exert a beneficial impact on the development and progression of renal disease as well cardiovascular disease.
Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab
Authors: Peira Elena , Chindamo Giulia , Chirio Daniela , Sapino Simona , Oliaro-Bosso Simonetta , Rebba Erica , Ivanchenko Pavlo , Gallarate Marina
Published: February 2021

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems.
Quality by Design Applied Development of Immediate-Release Rabeprazole Sodium Dry-Coated Tablet
Authors: Lee Sang-Ho , Kim Joo-Eun
Published: February 2021

The aim of this study was to develop immediate-release oral rabeprazole sodium tablets with rapid efficacy and gastric stability for the treatment of gastroesophageal reflux disease. Rabeprazole sodium is a commonly prescribed proton pump inhibitor; however, it is extremely unstable and degrades in acidic environments. Hence, it has been manufactured and supplied only in enteric-coated tablet form, while immediate-release (IR) formulations for this drug are very limited. In this study, we applied the quality by design (QbD) approach to formulate and optimize an IR dry-coated tablet containing rabeprazole sodium as an inner core with an outer sodium bicarbonate layer to stabilize the active pharmaceutical ingredient at gastric pH. We also investigated the stability of the pharmaceutical dosage form and its pharmacokinetic profile. The results show that the developed tablets are stable for approximately 12 months and have a high dissolution rate, greater than or equal to 90% at 30 min. Further, in vivo beagle pharmacokinetics confirmed that the newly developed IR tablet had an AUCt which is bioequivalent to the existing delayed-release rabeprazole tablet; however, its Tmax was 0.5 h, which is up to seven times faster than that of the existing tablet. Moreover, the IR tablet was found to immediately absorb in the stomach. Hence, the development of IR tablets can be used as a platform to overcome the technical and commercial limitations currently associated with various proton pump inhibitors used to treat patients with gastroesophageal reflux disease that require immediate therapeutic relief.
Understanding the Salt-Dependent Outcome of Glycine Polymorphic Nucleation
Authors: Han Guangjun , Chow Pui Shan , Tan Reginald B. H.
Published: February 2021

The salt-dependent polymorphs of glycine crystals formed from bulk solutions have been a longstanding riddle. In this study, in order to shed fresh light, we studied the effects of seven common salts on primary nucleation of the metastable α-glycine and the stable γ-glycine. Our nucleation experiments and in-depth data analyses enabled us to reveal that (NH4)2SO4, NaCl and KNO3, in general, promote γ-glycine primary nucleation very significantly while simultaneously inhibiting α-glycine primary nucleation, thereby explaining why these three salts induce γ-glycine readily. In comparison, Ca(NO3)2 and MgSO4 also promote γ-glycine and inhibit α-glycine primary nucleation but not sufficiently to induce γ-glycine. More interestingly, Na2SO4 and K2SO4 promote not only γ-glycine but also α-glycine primary nucleation, which is unexpected and presents a rare case where a single additive promotes the nucleation of both polymorphs. As a result, the promoting effects of Na2SO4 and K2SO4 on γ-glycine do not enable γ-glycine nucleation to be more competitive than α-glycine nucleation, with γ-glycine failing to appear. These observations help us to better understand salt-governed glycine polymorphic selectivity.