bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Toxoplasma gondii IgM Long Persistence: What Are the Underlying Mechanisms?
Authors: Vargas-Villavicencio José Antonio , Cañedo-Solares Irma , Correa Dolores
Published: August 2022

Diagnosis of Toxoplasma gondii acute infection was first attempted by detection of specific IgM antibodies, as for other infectious diseases. However, it was noted that this immunoglobulin declines slowly and may last for months or even years. Apart from the diagnostic problem imposed on clinical management, this phenomenon called our attention due to the underlying phenomena that may be causing it. We performed a systematic comparison of reports studying IgM antibody kinetics, and the data from the papers were used to construct comparative plots and other graph types. It became clear that this phenomenon is quite generalized, and it may also occur in animals. Moreover, this is not a technical issue, although some tests make more evident the prolonged IgM decay than others. We further investigated biological reasons for its occurrence, i.e., infection dynamics (micro-reactivation–encystment, reinfection and reactivation), parasite strain relevance, as well as host innate, natural B cell responses and Ig class-switch problems inflicted by the parasite. The outcomes of these inquiries are presented and discussed herein.
Vermiculite Modified with Fe3+ Polyhydroxy Cations Is a Low-Cost and Highly Available Adsorbent for the Removal of Phosphate Ions
Authors: do Nascimento Fernando H. , Masini Jorge C.
Published: August 2022

This paper demonstrates that intercalating Na+ homoionic vermiculite with Fe3+ polyhydroxy cations (1:1 molar ratio OH− to Fe3+) significantly improved the affinity of the clay mineral-based sorbent toward phosphate. Kinetic experiments revealed that adsorption is fast, approaching an equilibrium within about 200 min of contact time, and that the rate-limiting step is the intraparticle diffusion. Adsorption isotherms fitted to the Freundlich equation and a two-site Langmuir model, consistent with the heterogeneity of adsorption sites. The separation factor derived from the Langmuir constant revealed that the adsorption was favorable and even irreversible for high-affinity minor adsorption sites. The adsorption capacity was 299 ± 63 μmol g−1 (9.3 ± 2.1 mg P g−1), a value similar to several other clay-based phosphate adsorbents. Application to reservoir water spiked with 10 mg L−1 in P removed about 71% of the available phosphate.
CK2 Inhibition and Antitumor Activity of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines
Authors: Lyapustin Daniil N. , Kotovskaya Svetlana K. , Butorin Ilya I. , Ulomsky Evgeny N. , Rusinov Vladimir L. , Babkov Denis A. , Pokhlebin Alexander A. , Spasov Alexander A. , Melekhin Vsevolod V. , Tokhtueva Maria D. , Shcheglova Anna V. , Makeev Oleg G.
Published: August 2022

Today, cancer is one of the most widespread and dangerous human diseases with a high mortality rate. Nevertheless, the search and application of new low-toxic and effective drugs, combined with the timely diagnosis of diseases, makes it possible to cure most types of tumors at an early stage. In this work, the range of new polysubstituted 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines was extended. The structure of all the obtained compounds was confirmed by the data of 1H, 13C NMR spectroscopy, IR spectroscopy, and elemental analysis. These compounds were evaluated against human recombinant CK2 using the ADP-GloTM assay. In addition, the IC50 parameters were calculated based on the results of the MTT test against glioblastoma (A-172), embryonic rhabdomyosarcoma (Rd), osteosarcoma (Hos), and human embryonic kidney (Hek-293) cells. Compounds 5f, 5h, and 5k showed a CK2 inhibitory activity close to the reference molecule (staurosporine). The most potential compound in the MTT test was 5m with an IC50 from 13 to 27 µM. Thus, our results demonstrate that 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines are promising for further investigation of their antitumor properties.
New Benzimidazoles Targeting Breast Cancer: Synthesis, Pin1 Inhibition, 2D NMR Binding, and Computational Studies
Authors: Nashaat Samira , Henen Morkos A. , El-Messery Shahenda M. , Eisa Hassan
Published: August 2022

Benzimidazole derivatives are known to be key players in the development of novel anticancer agents. Herein, we aimed to synthesize novel derivatives to target breast cancer. A new series of benzimidazole derivatives conjugated with either six- and five-membered heterocyclic ring or pyrazanobenzimidazoles and pyridobenzimidazole linkers were synthesized yielding compounds 5–8 and 10–14, respectively. Structure elucidation of the newly synthesized compounds was achieved through microanalytical analyses and different spectroscopic techniques (1H, 13C-APT and 1H–1H COSY and IR) in addition to mass spectrometry. A biological study for the newly synthesized compounds was performed against breast cancer cell lines (MCF-7), and the most active compounds were further subjected to normal Human lung fibroblast (WI38) which indicates their safety. It was found that most of them exhibit high cytotoxic activity against breast cancer (MCF-7) and low cytotoxic activity against normal (WI38) cell lines. Compounds 5, 8, and 12, which possess the highest anti-breast cancer activity against the MCF-7 cell line, were selected for Pin1 inhibition assay using tannic acid as a reference drug control. Compound 8 was examined for its effect on cell cycle progression and its ability to apoptosis induction. Mechanistic evaluation of apoptosis induction was demonstrated by triggering intrinsic apoptotic pathways via inducing ROS accumulation, increasing Bax, decreasing Bcl-2, and activation of caspases 6, 7, and 9. Binding to 15N-labeled Pin1 enzyme was performed using state-of-the-art 15N–1H HSQC NMR experiments to describe targeting breast cancer on a molecular level. In conclusion, the NMR results demonstrated chemical shift perturbation (peak shifting or peak disappearance) upon adding compound 12 indicating potential binding. Molecular docking using ‘Molecular Operating Environment’ software was extremely useful to elucidate the binding mode of active derivatives via hydrogen bonding.
Impact of Tralopyril and Triazolyl Glycosylated Chalcone in Human Retinal Cells’ Lipidome
Authors: Vilas-Boas Cátia , Running Logan , Pereira Daniela , Cidade Honorina , Correia-da-Silva Marta , Atilla-Gokcumen Gunes Ekin , Aga Diana S.
Published: August 2022

Antifouling (AF) coatings containing booster biocides are used worldwide as one of the most cost-effective ways to prevent the attachment of marine organisms to submerged structures. Nevertheless, many of the commercial biocides, such as Econea® (tralopyril), are toxic in marine environments. For that reason, it is of extreme importance that new efficient AF compounds that do not cause any harm to non-target organisms and humans are designed. In this study, we measured the half-maximal inhibitory concentration (IC50) of a promising nature-inspired AF compound, a triazolyl glycosylated chalcone (compound 1), in an immortalized human retinal pigment epithelial cell line (hTERT-RPE-1) and compared the results with the commercial biocide Econea®. We also investigated the effects of these biocides on the cellular lipidome following an acute (24 h) exposure using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Our results showed that compound 1 did not affect viability in hTERT-RPE-1 cells at low concentrations (1 μM), in contrast to Econea®, which caused a 40% reduction in cell viability. In total, 71 lipids were found to be regulated upon exposure to 10 µM of both compounds. Interestingly, both compounds induced changes in lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress, but often in opposing directions. In general, Econea® exposure was associated with an increase in lipid concentrations, while compound 1 exposure resulted in lipid depletion. Our study showed that exposure to human cells at sublethal Econea® concentrations results in the modulation of several lipids that are linked to cell death and survival.
21 Fluorescent Protein-Based DNA Staining Dyes
Authors: Kim Yurie Tehee , Oh Hyesoo , Seo Myung Jun , Lee Dong Hyeun , Shin Jieun , Bong Serang , Heo Sujeong , Hapsari Natalia Diyah , Jo Kyubong
Published: August 2022

Fluorescent protein–DNA-binding peptides or proteins (FP-DBP) are a powerful means to stain and visualize large DNA molecules on a fluorescence microscope. Here, we constructed 21 kinds of FP-DBPs using various colors of fluorescent proteins and two DNA-binding motifs. From the database of fluorescent proteins (FPbase.org), we chose bright FPs, such as RRvT, tdTomato, mNeonGreen, mClover3, YPet, and mScarlet, which are four to eight times brighter than original wild-type GFP. Additionally, we chose other FPs, such as mOrange2, Emerald, mTurquoise2, mStrawberry, and mCherry, for variations in emitting wavelengths. For DNA-binding motifs, we used HMG (high mobility group) as an 11-mer peptide or a 36 kDa tTALE (truncated transcription activator-like effector). Using 21 FP-DBPs, we attempted to stain DNA molecules and then analyzed fluorescence intensities. Most FP-DBPs successfully visualized DNA molecules. Even with the same DNA-binding motif, the order of FP and DBP affected DNA staining in terms of brightness and DNA stretching. The DNA staining pattern by FP-DBPs was also affected by the FP types. The data from 21 FP-DBPs provided a guideline to develop novel DNA-binding fluorescent proteins.
Effects of Post-Harvest Elicitor Treatments with Ultrasound, UV- and Photosynthetic Active Radiation on Polyphenols, Glucosinolates and Antioxidant Activity in a Waste Fraction of White Cabbage (Brassica oleracea var. capitata)
Authors: Seljåsen Randi , Kusznierewicz Barbara , Bartoszek Agnieszka , Mølmann Jørgen , Vågen Ingunn M.
Published: August 2022

Biosynthesis of phytochemicals in leaves of Brassica can be initiated by abiotic factors. The aim of the study was to investigate elicitor treatments to add value to waste of cabbage. A leaf waste fraction from industrial trimming of head cabbage was exposed to UV radiation (250–400 nm, 59 and 99 kJ∙m−2, respectively), photosynthetic active radiation (PAR, 400–700 nm, 497 kJ∙m−2), and ultrasound in water bath (35 kHz, at 15, 30 and 61 kJ∙l−1 water), in order to improve nutraceutical concentration. UV was more effective than PAR to increase the level of flavonols (2 to 3-fold higher) and hydroxycinnamate monosaccharides (1 to 10-fold higher). PAR was three times as effective as UV to increase anthocyanins. Interaction of PAR + UV increased antioxidant activity (30%), the content of five phenolics (1.4 to 10-fold higher), and hydroxycinnamic monosaccharides (compared with PAR or UV alone). Indoles were reduced (40–52%) by UV, but the other glucosinolates (GLS) were unaffected. Ultrasound did not influence any parameters. The results are important for white cabbage by-products by demonstrating that UV + PAR can be successfully used as an effectual tool to increase important phenolics and antioxidant activity of waste fraction leaves without an adverse effect on the main GLS.
Discovery of Novel Cinnamide Fungicidal Leads with Optical Hydroxyl Side Chain
Authors: Wang Weiwei , Jiang Jiazhen , Zhang Zhenhua , Wang Mingan
Published: August 2022

In order to overcome the resistance of phytopathogens to commercial fungicides, a series of optical 2-methyl-2,3-diol-5-pentyl-based cinnamamide derivatives were rationally designed, synthesized, characterized, and evaluated for their in vitro and in vivo fungicidal activities. The bioassay results indicated that the EC50 (concentration for 50% of maximal effect) values of (R)-11f, (R)-11m, (S)-11m and (R)-11n were 0.16, 0.28, 0.41 and 0.47 µg/mL in the in vitro evaluation against Sclerotinia sclerotiorum, respectively, while compounds (R)- and (S)-11i, (R)- and (S)-11j exhibited excellent in vivo fungicidal activity against Pseudoperonspera cubensis with inhibition rates of 100% at 400 μg/mL. These findings supported the idea that optical 2-methyl-2,3-diol-5-pentyl-containing cinnamamides (R)- and (S)-11i, (R)- and (S)-11j with 2-chloro-4-trifluoromethyl aniline and 2-(4-chlorophenyl) aniline showed excellent in vivo fungicidal activity against S. sclerotiorum and P. cubensis and were promising fungicide candidates.
TPPS4—Sensitized Photooxidation of Micropollutants—Singlet Molecular Oxygen Kinetic Study
Authors: Gmurek Marta
Published: August 2022

Visible light-sensitized oxidation of micropollutants (MPs) in the presence of meso-tetrakis(4-sulfonatophenyl)porphyrin photosensitizers was studied. In order to explore the role of type I (ROS generation) or type II (singlet oxygen) photooxidation, radical scavengers were used to obtain insight into the mechanism of photodegradation. It was revealed that singlet oxygen is the main ROS taking part in TPPS4- sensitized photooxidation of micropollutants. The interaction of MPs with 1O2 in deuterium oxide (D2O) was investigated by measuring the phosphorescence lifetime of 1O2. The rate constant (kq) for the total (physical and chemical) quenching of 1O2 by MPs was determined in a D2O buffer (pD 7, 9 and 10.8). The rate constants of singlet oxygen quenching and reaction with MPs were determined, and the rate constant of excited TPPS4 quenching by MPs was also estimated.
Damage Location Monitoring of Graphene/Conducting Polymer Composites Film Based on Self-Sensing
Authors: Guo Huihui , Li Yuhang , Liu Tingting , Wu Zuquan
Published: August 2022

Conductive graphene polymer composites are considered promising functional materials in gas detection, strain detection, metal corrosion prevention, and electromagnetic wave absorption, owing to their good flexibility, lightweight, and adjustable conductivity. The internal defects or external damages of composite films will seriously affect the electrical and functional properties of the materials. Based on the conductive network inside the conductive polymer film and the self-inductance to ultrasonic wave, the defect self-monitoring system of the conductive polymer film is designed and optimized in this work. The self-damage detection system is composed of an electrode array, excitation source, resistance signal acquisition and processing circuit, and damage display. Aiming at different scenarios, the improved interdigital structure transducer for sensors and damage detection device for coating film with a large area are presented and optimized respectively. Meanwhile, the damage location algorithm based on time difference measurement and kernel density estimation algorithm is also optimized. The multiple damage detection is realized by a device with a 4 × 8 electrode array, and the relative error of damage area with 1 mm × 1 mm is less than 5%, and the lower detection limits of damage size are 0.3 mm × 0.3 mm.
Metabolic Obesity Phenotypes and Risk of Lung Cancer: A Prospective Cohort Study of 450,482 UK Biobank Participants
Authors: Shao Fang , Chen Yina , Xu Hongyang , Chen Xin , Zhou Jiawei , Wu Yaqian , Tang Yingdan , Wang Zhongtian , Zhang Ruyang , Lange Theis , Ma Hongxia , Hu Zhibin , Shen Hongbing , Christiani David C. , Chen Feng , Zhao Yang , You Dongfang
Published: August 2022

(1) Background: The association between metabolic obesity phenotypes and incident lung cancer (LC) remains unclear. (2) Methods: Based on the combination of baseline BMI categories and metabolic health status, participants were categorized into eight groups: metabolically healthy underweight (MHUW), metabolically unhealthy underweight (MUUW), metabolically healthy normal (MHN), metabolically unhealthy normal (MUN), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). The Cox proportional hazards model and Mendelian randomization (MR) were applied to assess the association between metabolic obesity phenotypes with LC risk. (3) Results: During a median follow-up of 9.1 years, 3654 incident LC patients were confirmed among 450,482 individuals. Compared with participants with MHN, those with MUUW had higher rates of incident LC (hazard ratio (HR) = 3.24, 95% confidence interval (CI) = 1.33–7.87, p = 0.009). MHO and MHOW individuals had a 24% and 18% lower risk of developing LC, respectively (MHO: HR = 0.76, 95% CI = 0.61–0.95, p = 0.02; MHO: HR = 0.82, 95% CI = 0.70–0.96, p = 0.02). No genetic association of metabolic obesity phenotypes and LC risk was observed in MR analysis. (4) Conclusions: In this prospective cohort study, individuals with MHOW and MHO phenotypes were at a lower risk and MUUW were at a higher risk of LC. However, MR failed to reveal any evidence that metabolic obesity phenotypes would be associated with a higher risk of LC.
Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids
Authors: Markowska Anna , Kurzawa Paweł , Bednarek Wiesława , Gryboś Anna , Mardas Marcin , Krzyżaniak Monika , Majewski Jan , Markowska Janina , Gryboś Marian , Żurawski Jakub
Published: August 2022

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.
Prevalence of Protein-Energy Wasting in Dialysis Patients Using a Practical Online Tool to Compare with Other Nutritional Scores: Results of the Nutrendial Study
Authors: Arias-Guillén Marta , Collado Silvia , Coll Elisabeth , Carreras Jordi , Betancourt Loreley , Romano Bárbara , Fernández Marisol , Duarte Verónica , Garro Julia , Soler Jordi , González Juan Carlos , Calabia Jordi
Published: August 2022

This cross-sectional study aims to explore the prevalence of protein-energy wasting (PEW) in dialysis patients in Catalonia, Spain, using a new and practical online tool which enables rapid calculation and comparison with other nutritional scores. Methods: A web tool (Nutrendial) was created to introduce different variables and automatically calculate PEW, Malnutrition inflammation Score (MIS) and Subjective Global Assessment (SGA) in 1389 patients (88% in haemodialysis (HD)), 12% in peritoneal dialysis (PD) from different regions of Catalonia. Results: A prevalence of 23.3% (26% HD, 10.2% PD) of PEW was found, with a mean MIS score of 6 and SGA score of C in 7% of the patients. ROC analysis showed MIS as the best nutritional score to diagnose PEW (AUC 0.85). Albumin delivered lower diagnostic precision (AUC 0.77) and sensitivity (66%). A cut off point of 7 (86% sensitivity and 75% specificity) for MIS and 3.7 mg/dL for albumin were found to predict the appearance of PEW in this population. SGA B or C showed an 87% sensitivity and 55% specificity to diagnose PEW. Very low nutritional intervention (14%) was recorded with this tool in patients with PEW. Conclusions: This new online tool facilitated the calculation of PEW, enabling different professionals—including nephrologists, dieticians and nurses—to efficiently obtain insights into the nutritional status of the Catalonian dialysis population and implement the required nutritional interventions. MIS is the score with more sensitivity to diagnose PEW.
Retail Cost and Energy Adjusted Cost Are Associated with Dietary Diversity and Nutrient Adequacy for Diets of 6–24 Months Children
Authors: Mulabisano Tshavhuyo A. , Laubscher Ria , Hoffman Marinel , Hill Jillian , Kunneke Ernesta , Smuts Cornelius M. , Faber Mieke
Published: August 2022

Poor nutrition during the first two years of life has long term consequences, but resource-poor households often do not have the means to access nutrient-dense and diverse diets. Pooled data of 24-h dietary recalls (n = 3336) and 2019 retail food prices were analyzed to determine associations of retail cost and energy cost (per 100 kcal) with diet quality indicators for diets of 6–24-month-old South African children who were breastfed (BF-diet) and not breastfed (NBF-diet) during the 24-h recall period. Compared to the BF-diet, retail cost for the NBF-diet was three times higher for age 6–11 months, and double for age 12–17 months. Higher retail cost and energy cost were both associated with higher mean adequacy ratios and dietary diversity scores for BF and NBF diets, except energy cost for the NBF-diet for age 6–11 months. Overall, inclusion of flesh foods, vitamin A-rich fruits and vegetables, and other fruit and vegetables increased from the lowest to the highest retail cost tertile. The higher cost of more nutritious diets highlights the importance of the affordability of diets in interventions aimed at improving diet quality. Possible strategies include: identifying the most-affordable foods within each food group, focusing on foods that provide multiple key micronutrients, and the inclusion of locally available indigenous foods.
The Impact of the COVID-19 Pandemic on Dietary Patterns of Pregnant Women: A Comparison between Two Mother-Child Cohorts in Sicily, Italy
Authors: Magnano San Lio Roberta , Barchitta Martina , Maugeri Andrea , La Rosa Maria Clara , Giunta Giuliana , Panella Marco , Cianci Antonio , Galvani Fabiola , Pappalardo Elisa , Ettore Giuseppe , Agodi Antonella
Published: August 2022

A maternal diet, before and during pregnancy, plays a key role in ensuring maternal and newborn health. The COVID-19 pandemic, however, may have compromised dietary habits in the general population and in specific subgroups of individuals. Here, we evaluated the impact of COVID-19 on the diet of pregnant women, using data from two mother-child cohorts in Sicily (Italy). Dietary data were collected using a food frequency questionnaire and analyzed through the Mediterranean diet (MD) score and principal component analysis (PCA). The comparison of maternal dietary consumption before and during the COVID-19 pandemic showed differences in terms of vegetables (p < 0.001), fruit (p < 0.001), dairy products (p < 0.001), fish (p < 0.001), and legumes (p = 0.001). Accordingly, after adjusting for covariates, mothers enrolled during the pandemic were more likely to report low adherence to MD than those enrolled before (OR = 1.65; 95%CI = 1.12–2.42; p = 0.011). A similar result was obtained by analyzing the adherence to a prudent dietary pattern, derived through PCA and characterized by high intake of cooked and row vegetables, legumes, fruit, fish, and soup. Overall, these findings suggested that the COVID-19 pandemic may have influenced maternal diet during pregnancy. However, further efforts are needed to investigate the main causes and consequences of this change.
Liraglutide and Exercise: A Possible Treatment for Obesity?
Authors: Macêdo Ana Paula Azevêdo , Vieira Renan Fudoli Lins , Brisque Guilherme Domingos , Abud Gabriela Ferreira , Pauli José Rodrigo
Published: August 2022

(1) Background: Obesity has become an important public health problem worldwide, and its characterization as a chronic disease reflects the impact of a complex and multifactorial condition. The treatment for obesity is based on lifestyle interventions that induce a negative energy balance. However, adherence to a lifestyle intervention is a challenge for many overweight and obese people. Thus, pharmacotherapy in the management of obesity is used to increase patient adherence to lifestyle changes and overcome the biological adaptations that occur with weight loss. Among these drugs, liraglutide stands out. Liraglutide is an analog of human glucagon-like peptide-1 (GLP-1), a hormone that regulates glucose-dependent insulin secretion, and glucagon release. (2) Results: Liraglutide appears to be effective in weight reduction and glycemic control in diabetic and obese patients, and combination of liraglutide and exercise can also bring benefits in weight loss. Furthermore, the combination of liraglutide and physical exercise can prevent adverse effects observed in the administration of liraglutide. (3) Conclusions: liraglutide seems to contribute to cardiometabolic improvement in obese individuals with or without diabetes, and the combination of liraglutide and physical exercise can prevent adverse effects observed in the administration of liraglutide.
Inhibition of Melanization by Kojic Acid Promotes Cell Wall Disruption of the Human Pathogenic Fungus Fonsecaea sp.
Authors: Pereira Jorge Augusto Leão , Moraes Lienne Silveira de , Sena Chubert Bernardo Castro de , Nascimento José Luiz Martins do , Rodrigues Ana Paula D. , Silva Silvia Helena Marques da , Silva Edilene O.
Published: August 2022

Chromoblastomycosis (CBM) is a chronic human subcutaneous mycosis caused by various aetiologic agents. CBM does not have an established treatment but may be managed using antifungal agents, surgical removal of the lesions, or cryotherapy. Kojic acid (KA), a known tyrosinase inhibitor with a variety of biological actions, including fungistatic action against the fungus Cryptococcus neoformans, mediated by inhibiting melanin production, seems to be an alternative to improve the treatment of CBM. The aim of the present study was to analyze the action of KA against the pathogenic fungus Fonsecaea sp., an aetiological agent of CBM. The fungal culture was incubated with KA, and the amount of melanin was assessed, followed by cytochemical detection. Subsequently, the samples were analyzed by light microscopy, transmission and scanning electron microscopy. Culture analysis revealed that 100 g/mL KA significantly decreased the melanization of the fungus and the exocytosis of melanin into the culture supernatant. Additionally, KA induced less growth of biofilm formation and intense disruption of the cell wall, and decreased the number of melanin-containing vesicles in the culture supernatant. Finally, KA inhibited fungal filamentation in culture and the subsequent phagocytosis process. Thus, KA may be a promising substance to help in the treatment of CBM.
High Predictive Value of the Soluble ZEBRA Antigen (Epstein-Barr Virus Trans-Activator Zta) in Transplant Patients with PTLD
Authors: Lupo Julien , Wielandts Anne-Sophie , Buisson Marlyse , Consortium CRYOSTEM , Habib Mohammed , Hamoudi Marwan , Morand Patrice , Verduyn-Lunel Frans , Caillard Sophie , Drouet Emmanuel
Published: August 2022

The ZEBRA (Z EBV replication activator) protein is the major transcription factor of EBV, expressed upon EBV lytic cycle activation. An increasing body of studies have highlighted the critical role of EBV lytic infection as a risk factor for lymphoproliferative disorders, such as post-transplant lymphoproliferative disease (PTLD). We studied 108 transplanted patients (17 PTLD and 91 controls), retrospectively selected from different hospitals in France and in the Netherlands. The majority of PTLD were EBV-positive diffuse large B-cell lymphomas, five patients experienced atypical PTLD forms (EBV-negative lymphomas, Hodgkin’s lymphomas, and T-cell lymphomas). Fourteen patients among the seventeen who developed a pathologically confirmed PTLD were sZEBRA positive (soluble ZEBRA, plasma level above 20 ng/mL, measured by an ELISA test). The specificity and positive predictive value (PPV) of the sZEBRA detection in plasma were 98% and 85%, respectively. Considering a positivity threshold of 20 ng/mL, the sensitivity of the sZEBRA was 82.35% and the specificity was 94.51%. The mean of the sZEBRA values in the PTLD cases were significantly higher than in the controls (p < 0.0001). The relevance of the lytic cycle and, particularly, the role of ZEBRA in lymphomagenesis is a new paradigm pertaining to the prevention and treatment strategies for PTLD. Given the high-specificity and the predictive values of this test, it now appears relevant to investigate the lytic EBV infection in transplanted patients as a prognostic biomarker.
Co-Occurrence of β-Lactam and Aminoglycoside Resistance Determinants among Clinical and Environmental Isolates of Klebsiella pneumoniae and Escherichia coli: A Genomic Approach
Authors: Altayb Hisham N. , Elbadawi Hana S. , Alzahrani Faisal A. , Baothman Othman , Kazmi Imran , Nadeem Muhammad Shahid , Hosawi Salman , Chaieb Kamel
Published: August 2022

The presence of antimicrobial-resistance genes (ARGs) in mobile genetic elements (MGEs) facilitates the rapid development and dissemination of multidrug-resistant bacteria, which represents a serious problem for human health. This is a One Health study which aims to investigate the co-occurrence of antimicrobial resistance determinants among clinical and environmental isolates of K. pneumoniae and E. coli. Various bioinformatics tools were used to elucidate the bacterial strains’ ID, resistome, virulome, MGEs, and phylogeny for 42 isolates obtained from hospitalized patients (n = 20) and environmental sites (including fresh vegetables, fruits, and drinking water) (n = 22). The multilocus sequence typing (MLST) showed that K. pneumoniae belonged to ten sequence types (STs) while the E. coli belonged to seventeen STs. Multidrug-resistant isolates harbored β-lactam, aminoglycoside resistance determinants, and MGE were detected circulating in the environment (drinking water, fresh vegetables, and fruits) and in patients hospitalized with postoperative infections, neonatal sepsis, and urinary tract infection. Four K. pneumoniae environmental isolates (7E, 16EE, 1KE, and 19KE) were multidrug-resistant and were positive for different beta-lactam and aminoglycoside resistance determinants. blaCTX-M-15 in brackets of ISEc 9 and Tn 3 transposases was detected in isolates circulating in the pediatrics unit of Soba hospital and the environment. This study documented the presence of bacterial isolates harboring a similar pattern of antimicrobial resistance determinants circulating in hospitals and environments. A rapid response is needed from stakeholders to initiate a program for infection prevention and control measures to detect such clones disseminated in the communities and hospitals.
Neuroprotective Effect of Morin Hydrate against Attention-Deficit/Hyperactivity Disorder (ADHD) Induced by MSG and/or Protein Malnutrition in Rat Pups: Effect on Oxidative/Monoamines/Inflammatory Balance and Apoptosis
Authors: Salem Hoda A. , Elsherbiny Nehal , Alzahrani Sharifa , Alshareef Hanan M. , Abd Elmageed Zakaria Y. , Ajwah Sadeem M. , Hamdan Ahmed M. E. , Abdou Yahia S. , Galal Omneya O. , El Azazy Marwa K. A. , Abu-Elfotuh Karema
Published: August 2022

Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)―a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals’ behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1β), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.
Efficacy of Kan Jang® in Patients with Mild COVID-19: Interim Analysis of a Randomized, Quadruple-Blind, Placebo-Controlled Trial
Authors: Ratiani Levan , Pachkoria Elene , Mamageishvili Nato , Shengelia Ramaz , Hovhannisyan Areg , Panossian Alexander
Published: August 2022

Kan Jang®, the fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim extracts, is a herbal medicinal product for relieving symptoms of upper respiratory tract infections. This study aimed to assess the efficacy of Kan Jang®/Nergecov® on duration and the relief of inflammatory symptoms in adults with mild COVID-19. 86 patients with laboratory-confirmed COVID-19 and mild symptoms for one to three days received supportive treatment (paracetamol) and six Kan Jang® (daily dose of andrographolides—90 mg) or placebo capsules a day for 14 consecutive days in this randomized, quadruple-blinded, placebo-controlled, two-parallel-group study. The primary efficacy outcomes were the decrease in the acute-phase duration and the severity of symptoms score (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles), an increase in cognitive functions, physical performance, quality of life, and decrease in IL-6, c-reactive protein, and D-dimer in blood. Kan Jang®/Nergecov® was effective in reducing the risk of progression to severe COVID-19, decreasing the disease progression rate by almost 2.5-fold compared to placebo. Absolute risk reduction by Kan Jang treatment is 14%, the relative risk reduction is 243.9%, and the number Needed to Treat is 7.14. Kan Jang®/Nergecov® reduces the duration of disease, virus clearance, and days of hospitalization and accelerates recovery of patients, relief of sore throat, muscle pain, runny nose, and normalization of body temperature. Kan Jang®/Nergecov® significantly relieves the severity of inflammatory symptoms such as sore throat, runny nose, and muscle pain, decreases pro-inflammatory cytokine IL-6 level in the blood, and increases patients’ physical performance (workout) compared to placebo. In this study, for the first time we demonstrate that Kan Jang®/Nergecov® is effective in treating mild COVID-19.
HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ
Authors: Miyajima Chiharu , Hayakawa Yurika , Inoue Yasumichi , Nagasaka Mai , Hayashi Hidetoshi
Published: August 2022

Transcriptional coactivator with PDZ-binding motif (TAZ) is a downstream transcriptional regulator of the Hippo pathway that controls cell growth and differentiation. The aberrant activation of TAZ correlates with a poor prognosis in human cancers, such as breast and colon cancers. We previously demonstrated that TAZ inhibited the tumor suppressor functions of p53 and enhanced cell proliferation. Statins, which are used to treat dyslipidemia, have been reported to suppress the activity of TAZ and exert anti-tumor effects. In the present study, we focused on the regulation of p53 functions by TAZ and investigated whether statins modulate these functions via TAZ. The results obtained suggest that statins, such as simvastatin and fluvastatin, activated the transcriptional function of p53 by suppressing TAZ protein expression. Furthermore, co-treatment with simvastatin and anti-tumor agents that cooperatively activate p53 suppressed cancer cell survival. These results indicate a useful mechanism by which statins enhance the effects of anti-tumor agents through the activation of p53 and may represent a novel approach to cancer therapy.
New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity
Authors: Talianová Veronika , Kejík Zdeněk , Kaplánek Robert , Veselá Kateřina , Abramenko Nikita , Lacina Lukáš , Strnadová Karolína , Dvořánková Barbora , Martásek Pavel , Masařík Michal , Megová Magdalena Houdová , Bušek Petr , Křížová Jana , Zdražilová Lucie , Hansíková Hana , Vlčák Erik , Filimonenko Vlada , Šedo Aleksi , Smetana Karel , Jakubek Milan
Published: August 2022

IL-6 signaling is involved in the pathogenesis of a number of serious diseases, including chronic inflammation and cancer. Targeting of IL-6 receptor (IL-6R) by small molecules is therefore an intensively studied strategy in cancer treatment. We describe the design, synthesis, and characteristics of two new bis-pentamethinium salts 5 and 6 (meta and para) bearing indole moieties. Molecular docking studies showed that both compounds have the potential to bind IL-6R (free energy of binding −9.5 and −8.1 kcal/mol). The interaction with IL-6R was confirmed using microscale thermophoresis analyses, which revealed that both compounds had strong affinity for the IL-6R (experimentally determined dissociation constants 26.5 ± 2.5 nM and 304 ± 27.6 nM, respectively). In addition, both compounds were cytotoxic for a broad spectrum of cancer cell lines in micromolar concentrations, most likely due to their accumulation in mitochondria and inhibition of mitochondrial respiration. In summary, the structure motif of bis-pentamethinium salts represents a promising starting point for the design of novel multitargeting compounds with the potential to inhibit IL-6 signaling and simultaneously target mitochondrial metabolism in cancer cells.
Emerging Bioactive Agent Delivery-Based Regenerative Therapies for Lower Genitourinary Tissues
Authors: Da Lin-Cui , Sun Yan , Lin Yun-Hong , Chen Su-Zhu , Chen Gang-Xin , Zheng Bei-Hong , Du Sheng-Rong
Published: August 2022

Injury to lower genitourinary (GU) tissues, which may result in either infertility and/or organ dysfunctions, threatens the overall health of humans. Bioactive agent-based regenerative therapy is a promising therapeutic method. However, strategies for spatiotemporal delivery of bioactive agents with optimal stability, activity, and tunable delivery for effective sustained disease management are still in need and present challenges. In this review, we present the advancements of the pivotal components in delivery systems, including biomedical innovations, system fabrication methods, and loading strategies, which may improve the performance of delivery systems for better regenerative effects. We also review the most recent developments in the application of these technologies, and the potential for delivery-based regenerative therapies to treat lower GU injuries. Recent progress suggests that the use of advanced strategies have not only made it possible to develop better and more diverse functionalities, but also more precise, and smarter bioactive agent delivery systems for regenerative therapy. Their application in lower GU injury treatment has achieved certain effects in both patients with lower genitourinary injuries and/or in model animals. The continuous evolution of biomaterials and therapeutic agents, advances in three-dimensional printing, as well as emerging techniques all show a promising future for the treatment of lower GU-related disorders and dysfunctions.
Unequal Behaviour between Hydrolysable Functions of Nirmatrelvir under Stress Conditions: Structural and Theoretical Approaches in Support of Preformulation Studies
Authors: Secretan Philippe-Henri , Annereau Maxime , Kini-Matondo Willy , Prost Bastien , Prudhomme Jade , Bournane Lina , Paul Muriel , Yagoubi Najet , Sadou-Yayé Hassane , Do Bernard
Published: August 2022

Nirmatrelvir is an antiviral drug approved for the treatment of COVID-19. The available dosage form consists of tablets marketed under the brand name PAXLOVID®. Although knowledge of nirmatrelvir’s intrinsic stability may be useful for any potential development of other pharmaceutical forms, no data regarding this matter is available to date. Preliminary forced degradation studies have shown that the molecule is stable under oxidative and photolytic conditions, while hydrolytic conditions, both acidic and basic, have proven deleterious. Indeed, the molecule presents a priori several functions that can undergo hydrolysis, i.e., three amide moieties and a nitrile function. However, considering the degradation products formed under forced conditions and which were detected and identified by LC-UV-HRMSn, the hydrolysis process leading to their formation is selective since it involved only 2 of the 4 hydrolysable functions of the molecule. Ab initio studies based on density functional theory (DFT) have helped better understand these reactivity differences in aqueous media. Some hydrolyzable functions of nirmatrelvir differ from others in terms of electrostatic potential and Fukui functions, and this seems to correlate with the forced degradation outcomes.
Mechanistic Insights into Graphene Oxide Driven Photocatalysis as Co-Catalyst and Sole Catalyst in Degradation of Organic Dye Pollutants
Authors: Prakash Jai
Published: August 2022

Photocatalysis is a promising route to utilize sunlight, which has been potentially used to solve energy as well as environmental problems with an emphasis on fundamental understanding and technological applications in society. Semiconductors are excellent photocatalysts but often show less efficient activities due to the fast recombination of photogenerated charge carriers and very slow kinetics of surface photochemical reactions. However, recent advancements show promising strategies to improve their photocatalytic activities, including surface modifications using suitable co-catalysts and the development of novel efficient photocatalysts. Graphene oxide (GO) is one of such nanomaterials which shows multifarious roles in photocatalysis with a great potential to act as an independent solar-driven sole photocatalyst. In this minireview, the photochemistry of GO has been discussed in view of its multifarious roles/mechanisms in improving the photocatalytic activity of metal oxide semiconductors, plasmonic nanomaterials, and also their nanocomposites. In addition, recent advancements and applications of such GO-based photocatalysts in photocatalytic degradation of organic dye pollutants, including engineering of GO as the sole photocatalyst, have been discussed. Furthermore, the challenges and future prospects for the development of GO-based photocatalysts are discussed.
Exciton Transfer Dynamics and Annihilation in Rubidium–Cesium-Alloyed, Quasi-Two-Dimensional Perovskite
Authors: Abdelrazik Lamiaa , Jašinskas Vidmantas , Podlipskas Žydrūnas , Aleksiejūnas Ramūnas , Tamulaitis Gintautas , Gulbinas Vidmantas , Vyšniauskas Aurimas
Published: August 2022

Light-emitting diodes (LEDs) based on perovskite materials are a new group of devices that are currently undergoing rapid development. A significant fraction of these devices is based on quasi-2D perovskites fabricated with large organic cations. In this work, we describe the ultrafast scale dynamics in a quasi-2D PEA2(Rb0.6Cs0.4)2Pb3Br10 perovskite material with an excess of RbBr, which was previously used to fabricate blue-emitting perovskite LEDs. The results obtained using transient absorption spectroscopy are consistent with the assumption that the carrier dynamics in this material are dominated by excitons, most of which decay by exciton–exciton annihilation when high-intensity excitation is used. Furthermore, a slow energy transfer between different quasi-2D domains taking place within 50 ps was observed. The content of the RbBr did not show any strong influence on the observed dynamics. Our results show that the exciton–exciton annihilation proceeds much faster in thin (n = 2) quasi-2D domains than in thick (n ≥ 4) domains. This finding implies that perovskites with high-n, quasi-2D domains are preferable for efficient perovskite lasers and bright perovskite LEDs.
Nematicidal Screening of Aqueous Extracts from Plants of the Yucatan Peninsula and Ecotoxicity
Authors: Aviles-Gomez Jesús , Cristóbal-Alejo Jairo , Andrés María Fé , González-Coloma Azucena , Carnevali Germán , Pérez-Brito Daisy , Moo-Koh Felicia Amalia , Gamboa-Angulo Marcela
Published: August 2022

Active metabolites from plants are considered safer than synthetic chemicals for the control of plant-parasitic nematodes of the genus Meloidogyne. In the present work, 75 aqueous extracts (AEs) from different vegetative parts of 34 native plant species of the Yucatan Peninsula were evaluated against second-stage juveniles (J2s) of Meloidogyne incognita and M. javanica in microdilution assays. The highest mortality (M) against both Meloidogyne species was produced by the foliar AE from Alseis yucatanensis (M ≥ 94%) and Helicteres baruensis (M ≥ 77%) at 3% w/v after 72 h. Other active AEs at 3% were from the leaves of Croton itzaeus and stems of H. baruensis (M: 87–90%) on M. javanica and the stems of Annona primigenia and the leaves of Morella cerifera on M. incognita (M: 92–97%). The AEs from A. yucatanensis had the lowest LD50 against M. incognita (0.36% w/v), and against M. javanica (3.80% w/v). In an acute ecotoxicity assay of the most promising AEs using non-target earthworms (Eisenia fetida), the AE of A. yucatanensis had slight acute toxicity (LD50: 2.80% w/v), and the rest of the most active AEs were not ecotoxic. These tropical plants are potential candidates for further studies as biorational agents for controlling Meloidogyne species.