bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression Analysis of Molecular Chaperones Hsp70 and Hsp90 on Development and Metabolism of Different Organs and Testis in Cattle (Cattle–yak and Yak)
Authors: Cui Yan , Liu Penggang , Yu Sijiu , He Junfeng , Afedo Seth Y. , Zou Shengnan , Zhang Qian , Liu Jun , Song Liangli , Xu Yuanfang , Wang Ting , Li Hui
Published: November 2022

Hsp70 and Hsp90 play an important role in testis development and spermatogenesis regulation, but the exact connection between Hsp70 and Hsp90 and metabolic stress in cattle is unclear. Here, we focused on the male cattle–yak and yak, investigated the expression and localization of Hsp70 and Hsp90 in their tissues, and explored the influence of these factors on development and metabolism. In our study, a total of 54 cattle (24 cattle–yaks and 30 yaks; aged 1 day to 10 years) were examined. The Hsp90 mRNA of the cattle–yak was first cloned and compared with that of the yak, and variation in the amino acid sequence was found, which led to differences in protein spatial structure. Using real-time quantitative PCR (RT-qPCR) and Western blot (WB) techniques, we investigated whether the expression of Hsp70 and Hsp90 mRNA and protein are different in the cattle–yak and yak. We found a disparity in Hsp70 and Hsp90 mRNA and protein expression in different non-reproductive organs and in testicular tissues at different stages of development, while high expression was observed in the testes of both juveniles and adults. Moreover, it was intriguing to observe that Hsp70 expression was significantly high in the yak, whereas Hsp90 was high in the cattle–yak (p < 0.01). We also examined the location of Hsp70 and Hsp90 in the testis by immunohistochemical (IHC) and immunofluorescence (IF) techniques, and the results showed that Hsp70 and Hsp90 were positive in the epithelial cells, spermatogenic cells, and mesenchymal cells. In summary, our study proved that Hsp70 and Hsp90 expressions were different in different tissues (kidney, heart, cerebellum, liver, lung, spleen, and testis), and Hsp90 expression was high in the testis of the cattle–yak, suggesting that dysplasia of the cattle–yak may correlate with an over-metabolism of Hsp90.
Report on Vincristine-Producing Endophytic Fungus Nigrospora zimmermanii from Leaves of Catharanthus roseus
Authors: Birat Kanchan , Binsuwaidan Reem , Siddiqi Tariq Omar , Mir Showkat Rasool , Alshammari Nawaf , Adnan Mohd , Nazir Rahila , Ejaz Bushra , Malik Moien Qadir , Dewangan Rikeshwer Prasad , Ashraf Syed Amir , Panda Bibhu Prasad
Published: November 2022

Vincristine is an anti-cancer compound and one of the most crucial vinca alkaloids produced by the medicinal plant Catharanthus roseus (L.) G. Don. (Apocynaceae). This plant is home to hundreds of endophytic microbes, which produce a variety of bioactive secondary metabolites that are known for their medicinal properties. In this study, we focused on isolating an endophytic fungus that could increase the yield of vincristine under laboratory conditions as an alternative to plant-mediated extraction of vincristine. The endophytic fungus Nigrospora zimmermanii (Apiosporaceae) was isolated from Catharanthus roseus and it was found to be producing the anticancer compound vincristine. It was identified using high-performance thin-layer chromatography by matching the Rf value and spectral data with the vincristine standard and mass spectrometry data and the reference molecule from the PubChem database. The generation study of this microbe showed that the production of vincristine in the parent fungus was at its maximum, i.e., 5.344 µg/mL, while it was slightly reduced in subsequent generations. A colonization study was also performed and it showed that the fungus N. zimmermanii was able to re-infect the plant Catharanthus roseus after 20 days of inoculation. The colonization study showed that N. zimmernanii could infect the plant after isolation. This method is an efficient and easy way to obtain a high yield of vincristine, as compared to plant-mediated production.
Body Weight and Metabolic Rate Changes in Narcolepsy: Current Knowledge and Future Directions
Authors: Dhafar Hamza O. , BaHammam Ahmed S.
Published: November 2022

Narcolepsy is a known auto-immune disease that presents mainly in the teenage years with irresistible sleep attacks. Patients with narcolepsy, especially NT1, have been found to have a high prevalence of obesity and other metabolic derangements. This narrative review aimed to address the relationship between narcolepsy and changes in weight and metabolic rate, and discuss potential mechanisms for weight gain and metabolic changes and future research agendas on this topic. This article will provide a balanced, up-to-date critical review of the current literature, and delineate areas for future research, in order to understand the pathophysiological metabolic changes in narcolepsy. Articles using predefined keywords were searched for in PubMed and Google Scholar databases, with predefined inclusion and exclusion criteria. Compared to controls, patients with narcolepsy are more likely to be obese and have higher BMIs and waist circumferences. According to recent research, weight gain in narcolepsy patients may be higher during the disease’s outset. The precise mechanisms causing this weight gain remains unknown. The available information, albeit limited, does not support differences in basal or resting metabolic rates between patients with narcolepsy and controls, other than during the time of disease onset. The evidence supporting the role of orexin in weight gain in humans with narcolepsy is still controversial, in the literature. Furthermore, the available data did not show any appreciable alterations in the levels of CSF melanin-concentrating hormone, plasma and CSF leptin, or serum growth hormone, in relation to weight gain. Other mechanisms have been proposed, including a reduction in sympathetic tone, hormonal changes, changes in eating behavior and physical activity, and genetic predisposition. The association between increased body mass index and narcolepsy is well-recognized; however, the relationship between narcolepsy and other metabolic measures, such as body fat/muscle distribution and metabolic rate independent of BMI, is not well documented, and the available evidence is inconsistent. Future longitudinal studies with larger sample sizes are needed to assess BMR in patients with narcolepsy under a standard protocol at the outset of narcolepsy, with regular follow-up.
Shifts in Product Distribution in Microwave Plasma Methane Pyrolysis Due to Hydrogen and Nitrogen Addition
Authors: Wnukowski Mateusz , Gerber Julia , Mróz Karolina
Published: November 2022

Methane pyrolysis can produce many valuable products besides hydrogen, e.g., C2 compounds or carbon black. In the conditions provided by microwave plasma, the distribution of these products might be shifted by the addition of hydrogen and nitrogen. In this work, different ratios of H2:CH4, ranging from 0:1 to 4:1, were tested. The most unambiguous and promising result was obtained for the highest H2:CH4 ratio. For this ratio, a significant improvement in methane conversion rate was observed (from 72% to 95%) along with the increase in C2H2 and C2H4 yield and selectivity. The results support the hypothesis that the H radicals present in the plasma are responsible for improving methane conversion, while the presence of molecular hydrogen shifts the product distribution towards C2 compounds. Based on the carbon balance, the increase in the output of C2 compounds was obtained at the cost of solid carbon. At the same time, the addition of hydrogen resulted in the formation of bigger carbon particles. Finally, with the addition of both nitrogen and hydrogen, the formation of carbon was completely inhibited. Hydrogen cyanide was the main product formed instead of soot and some of the acetylene.
Influence of Post Heat Treatment Condition on Corrosion Behavior of 18Ni300 Maraging Steel Manufactured by Laser Powder Bed Fusion
Authors: Bae Kichang , Shin Dongmin , Kim Jun-Ho , Lee Wookjin , Jo Ilguk , Lee Junghoon
Published: November 2022

Laser powder bed fusion (LPBF) is a promising additive-manufacturing process for metallic materials. It has the advantage of flexibility in product design, such that various mechanical parts can be fabricated. However, because metal parts are built-up in a layer-by-layer manner, the material fabricated by LPBF has an anisotropic microstructure, which is important for the design of materials. In this study, the corrosion resistance of 18Ni300 maraging steel (MS) fabricated by LPBF was explored considering the building direction. Furthermore, the effects of heat treatment and aging on the microstructure and corrosion resistance were investigated. Sub-grain cells formed by rapid cooling in LPBF improve the corrosion resistance of MS. As a result, the as-built MS has the highest corrosion resistance. However, the sub-grain cells are eliminated by heat treatment or aging, which causes the deterioration of corrosion resistance. In the case of 18Ni300 MS, the cylindrical sub-grain cells are formed and aligned along the heat dissipation direction, which is similar to the building direction; thus, a significant anisotropy in corrosion resistance is found in the as-built MS. However, such anisotropy in corrosion resistance is diminished by heat treatment and aging, which eliminates the sub-grain cells.
Genosensing Applications of Glassy Carbon Electrodes Modified with Multi-Walled Carbon Nanotubes Non-Covalently Functionalized with Polyarginine
Authors: Gallay Pablo , López Mujica Michael , Bollo Soledad , Rivas Gustavo
Published: November 2022

We report the advantages of glassy carbon electrodes (GCE) modified with multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with polyarginine (PolyArg) for the adsorption and electrooxidation of different DNAs and the analytical applications of the resulting platform. The presence of the carbon nanostructures, and mainly the charge of the PolyArg that supports them, facilitates the adsorption of calf-thymus and salmon sperm double-stranded DNAs and produces an important decrease in the overvoltages for the oxidation of guanine and adenine residues and a significant enhancement in the associated currents. As a proof-of-concept of possible GCE/MWCNTs-PolyArg biosensing applications, we develop an impedimetric genosensor for the quantification of microRNA-21 at femtomolar levels, using GCE/MWCNTs-PolyArg as a platform for immobilizing the DNA probe, with a detection limit of 3fM, a sensitivity of 1.544 × 103 Ω M−1, and a successful application in enriched biological fluids.
Surface Spectroscopy of Pyrite Obtained during Grinding and Its Magnetisation
Authors: Reyes Martín , Herrera Guadalupe , Escudero Ramiro , Patiño Francisco , Reyes Iván A. , Flores Mizraim , Palacios Elia G. , Juárez Julio , Barrientos Francisco
Published: November 2022

During grinding with forged steel media, sulphides such as pyrite undergo surface changes due to the occurrence of oxidation–reduction reactions, which affect its depression during the concentration process. For this reason, in this work, the surface modification of pyrite during grinding was studied; FTIR, ICP-OES, XRD and SEM-EDS were used for the materials’ characterisation. It was found that the pyrite obtained during grinding showed magnetic susceptibility due to the absorption and superficial formation of magnetite Fe3O4, Fe–O bonds identified by FTIR at 598 cm−1, and of other species, such as oxy-hydroxy-sulphates at 696 cm−1 and goethite α-FeOOH at 875 cm−1. This caused the reversal of the zeta potential magnitude (ζ) from positive to negative at pH 8.3 and 30 min of grinding. The ζ of the pyrite throughout the studied pH ranges was, overall, positive, i.e., +5 mV. However, at pH 10.5 and 15 min of grinding, the ζ turned negative. This was associated with the formation of Fe–CO3 (−2) bonds in the siderite, which were identified with the absorption bands corresponding to 756, 1448 and 1493 cm−1.
Numerical Investigation of Photo-Generated Carrier Recombination Dynamics on the Device Characteristics for the Perovskite/Carbon Nitride Absorber-Layer Solar Cell
Authors: Saeed Faisal , Haseeb Khan Muhammad , Tauqeer Haider Ali , Haroon Asfand , Idrees Asad , Shehrazi Syed Mzhar , Prokop Lukas , Blazek Vojtech , Misak Stanislav , Ullah Nasim
Published: November 2022

The nitrogenated holey two-dimensional carbon nitride (C2N) has been efficaciously utilized in the fabrication of transistors, sensors, and batteries in recent years, but lacks application in the photovoltaic industry. The C2N possesses favorable optoelectronic properties. To investigate its potential feasibility for solar cells (as either an absorber layer/interface layer), we foremost detailed the numerical modeling of the double-absorber-layer–methyl ammonium lead iodide (CH3NH3PbI3) –carbon nitride (C2N) layer solar cell and subsequently provided in-depth insight into the active-layer-associated recombination losses limiting the efficiency (η) of the solar cell. Under the recombination kinetics phenomena, we explored the influence of radiative recombination, Auger recombination, Shockley Read Hall recombination, the energy distribution of defects, Band Tail recombination (Hoping Model), Gaussian distribution, and metastable defect states, including single-donor (0/+), single-acceptor (−/0), double-donor (0/+/2+), double-acceptor (2/−/0−), and the interface-layer defects on the output characteristics of the solar cell. Setting the defect (or trap) density to 1015cm−3 with a uniform energy distribution of defects for all layers, we achieved an η of 24.16%. A considerable enhancement in power-conversion efficiency ( η~27%) was perceived as we reduced the trap density to 1014cm−3 for the absorber layers. Furthermore, it was observed that, for the absorber layer with double-donor defect states, the active layer should be carefully synthesized to reduce crystal-order defects to keep the total defect density as low as 1017cm−3 to achieve efficient device characteristics.
Association of 100% Fruit Juice Consumption with Cognitive Measures, Anxiety, and Depression in US Adults
Authors: Agarwal Sanjiv , Fulgoni Victor L. , Jacques Paul F.
Published: November 2022

Cognitive decline, anxiety, and depression are significant contributors to human ill health and decreased quality of life. Intake of fruits including 100% juice is associated with beneficial effects on several health outcomes. The current study explored the potential associations between consumption of 100% fruit juice and neurocognitive markers in adults. Twenty-four-hour dietary recall data from the National Health and Nutrition Examination Survey (NHANES) 1988–1994, 1999–2018 for adults 20+ years (N = 62,606) were used to assess 100% fruit juice intake, and NHANES questionnaire data were used for the assessment of neurocognition. Association of usual intake of 100% fruit juice with neurocognitive outcomes were assessed by regression analysis after adjusting for demographic, lifestyle, dietary, and health-related covariates. About 21% of adults were fruit juice consumers and the intake was a little over 2 oz per day. Consumers of 100% fruit juice had 16.3% fewer days per month of feeling anxious compared to non-consumers. There were no significant associations of 100% fruit juice usual intake with other neurocognitive measures. A large number of potential confounding variables have been identified to be associated with one or more neurocognitive measures suggesting that these may be important parameters to include in future studies.
Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data
Authors: Kang Ho Suk , Kim So Young , Choi Hyo Geun , Lim Hyun , Kim Joo-Hee , Kim Ji Hee , Cho Seong-Jin , Nam Eun Sook , Min Kyueng-Whan , Park Ha Young , Kim Nan Young , Choi Younghee , Kwon Mi Jung
Published: November 2022

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (>20 years) based on the Korean Genome and Epidemiology Study data (2005–2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.
Correction: Machado et al. The Effect of Curcumin on Renal Ischemia/Reperfusion Injury in Diabetic Rats. Nutrients 2022, 14, 2798
Authors: Machado Douglas Ikedo , de Oliveira Silva Eloiza , Ventura Sara , Vattimo Maria de Fátima Fernandes
Published: November 2022

In the original publication [...]
A Rapid Review of the Impact of Family-Based Digital Interventions for Obesity Prevention and Treatment on Obesity-Related Outcomes in Primary School-Aged Children
Authors: Chai Li , Farletti Rebecca , Fathi Leila , Littlewood Robyn
Published: November 2022

Virtual delivery of obesity prevention and treatment programs may be effective for supporting children and families to adopt healthy lifestyle changes while enhancing program accessibility. This rapid review aimed to summarize the impact of family-based digital interventions for childhood obesity prevention and treatment. Four databases were searched up to February 2021 for trials of interactive digital programs aimed to prevent and/or treat obesity in children aged 5–12 years and reported diet, physical activity, sedentary behavior, sleep, or weight-related outcomes in children. A total of 23 publications (from 18 interventions) were included. Behavior change theories were used in 13 interventions with “Social Cognitive Theory” applied most frequently (n = 9). Interventions included websites (n = 11), text messaging (n = 5), video gaming (n = 2), Facebook (n = 3), and/or mobile applications (n = 2). Studies reported changes in body mass index (BMI; n = 11 studies), diet (n = 11), physical activity (n = 10), screen time (n = 6), and/or sleep (n = 1). Significant improvements were reported for diet (n = 5) or physical activity (n = 4). Two of the six interventions were effective in reducing screen time. Digital interventions have shown modest improvements in child BMI and significant effectiveness in diet and physical activity, with emerging evidence supporting the use of social media and video gaming to enhance program delivery.
Percutaneous Radiology Gastrostomy (PRG)-Associated Complications at a Tertiary Hospital over the Last 25 Years
Authors: Piñar-Gutiérrez Ana , Serrano-Aguayo Pilar , García-Rey Silvia , Vázquez-Gutiérrez Rocío , González-Navarro Irene , Tatay-Domínguez Dolores , Garrancho-Domínguez Pilar , Remón-Ruiz Pablo J. , Martínez-Ortega Antonio J. , Nacarino-Mejías Verónica , Iglesias-López Álvaro , Pereira-Cunill José Luis , García-Luna Pedro Pablo
Published: November 2022

Objectives: We aimed to describe and compare the complications associated with different percutaneous radiologic gastrostomy (PRG) techniques. Methods: A retrospective and prospective observational study was conducted. Patients who underwent a PRG between 1995–2020 were included. Techniques: A pigtail catheter was used until 2003, a balloon catheter without pexy was used between 2003–2009 and a balloon catheter with gastropexy was used between 2015–2021. For the comparison of proportions, X2 tests or Fisher’s test were used when necessary. Univariate analysis was performed to study the risk factors for PRG-associated complications. Results: n = 330 (pigtail = 114, balloon-type without pexy = 28, balloon-type with pexy = 188). The most frequent indication was head and neck cancer. The number of patients with complications was 44 (38.5%), 11 (39.2%) and 54 (28,7%), respectively. There were seven (25%) cases of peritonitis in the balloon-type without-pexy group and 1 (0.5%) in the balloon-type with-pexy group, the latter being the only patient who died in the total number of patients (0.3%). Two (1%) patients of the balloon-type with-pexy group presented with gastrocolic fistula. The rest of the complications were minor. Conclusions: The most frequent complications associated with the administration of enteral nutrition through PRG were minor and the implementation of the balloon-type technique with pexy has led to a decrease in them.
Professional Male Beach Handball Players Performance Profile
Authors: Martínez-Rodríguez Alejandro , Sánchez-Sánchez Javier , Martínez-Olcina María , Vicente-Martínez Manuel , Yáñez-Sepúlveda Rodrigo , Cortés-Roco Guillermo , Vázquez-Diz Juan Antonio , Sánchez-Sáez Juan Antonio
Published: November 2022

Beach handball is a sport that has seen an increase in the number of players in the last decade. The aim of the study was to evaluate the basic measures of body composition, maturation, performance outcomes and the adherence to the Mediterranean diet of professional beach handball players, as a function of category (junior vs. senior) and playing positions. Thirty-six professional beach handball players participated in the study: 18 seniors (age: 25.0 ± 5.19) and 18 juniors (age: 16.7 ± 0.46); Each player’s body composition and different sports performance variables were analysed using the CMJ test, the Abalakov test, the Yo-Yo Test IR1 and the handgrip test. The Mediterranean diet Adherence was analysed using the KIDMED questionnaire. Significant differences are observed for all performance variables, with the values of senior players being higher in all cases (p < 0.005). Moreover, the adherence to the Mediterranean diet is moderate. Positive correlations were observed between the CMJ and weight (p = 0.012) and the CMJ and the BMI (p = 0.003). The same was observed for the Abalakov test, with p = 0.004 for weight and p = 0.001 for the BMI. Regarding the dynamometry, it positively correlates with the height (p = 0.002), the sitting height (p = 0.008), wingspan (p < 0.001) and weight (p = 0.011). The opposite occurred with the Yo-Yo Test and the KIDMED variables. Conclusions: One aspect to improve, as a key performance factor, would be the adherence to the Mediterranean diet for both categories. Players with a better adherence, achieved better results in the performance tests.
Are Caffeine’s Effects on Resistance Exercise and Jumping Performance Moderated by Training Status?
Authors: Berjisian Erfan , Naderi Alireza , Mojtahedi Shima , Grgic Jozo , Ghahramani Mohammad Hossein , Karayigit Raci , Forbes Jennifer L. , Amaro-Gahete Francisco J. , Forbes Scott C.
Published: November 2022

This study aimed to explore if the effects of caffeine intake on resistance exercise and jumping performance are moderated by training status. We included ten resistance-trained and ten recreationally active males in a randomized, double-blind, crossover study. Participants were categorized into groups according to their resistance to training experience and muscular strength levels. Exercise performance outcomes included weight lifted and mean velocity during a one-repetition maximum (1RM) bench press and squat; repetitions were performed to muscular failure in the same exercises with 70% of 1RM and countermovement jump (CMJ) height. Exercise performance was evaluated on three occasions, following no substance ingestion (control), caffeine (6 mg/kg), and placebo. There was a main effect on the condition for all the performance outcomes (all p ≤ 0.02), except for the 1RM squat mean velocity (p = 0.157) and 1RM bench press mean velocity (p = 0.719). For weight lifted in the 1RM bench press, there was a significant difference when comparing the caffeine vs. control, caffeine vs. placebo, and placebo vs. control. For weight lifted in the 1RM squat, a significant difference was found when comparing the caffeine vs. control. For muscular endurance outcomes and jump height, a significant difference was found when caffeine was compared to the control or placebo. Effect sizes were trivial for muscular strength (Hedges’ g: 0.04–0.12), small for the jump height (Hedges’ g: 0.43–0.46), and large for muscular endurance (Hedges’ g: 0.89–1.41). Despite these ergogenic effects, there was no significant training status × caffeine interaction in any of the analyzed outcomes. In summary, caffeine ingestion is ergogenic for muscular strength, endurance, and jump height. These effects are likely to be of a similar magnitude in resistance-trained and recreationally active men.
Serum Phosphate Levels Modify the Impact of FGF23 Levels on Hemoglobin in Chronic Kidney Disease
Authors: Navarro-González Juan F. , Mora-Fernández Carmen , Diaz-Tocados Juan Miguel , Bozic Milica , Bermúdez-López Marcelino , Martín Marisa , Valdivielso Jose Manuel
Published: November 2022

Anemia is a complication of chronic kidney disease (CKD). Phosphate and fibroblast growth factor-23 (FGF23) have a close relationship, as both are related to the pathogenesis of anemia. However, the possible interplay between them regarding their effect on anemia has not been evaluated. This was a cross-sectional study of 896 participants from the NEFRONA study (273 CKD3, 246 CKD4-5, 282 dialysis and 95 controls). The levels of 25(OH) and 1,25(OH)2 vitamin D, intact FGF23 (iFGF23) and soluble Klotho were measured, together with standard blood biochemistries. Anemia was defined as hemoglobin levels < 13 g/dL in men and <12 g/dL in women. Patients with anemia (407, 45.4%) were younger, mostly men and diabetic; were in advanced CKD stages; had lower calcium, 1,25(OH)2 vitamin D and albumin levels; and had higher ferritin, phosphate, intact PTH, and iFGF23. An inverse correlation was observed between hemoglobin and both iFGF23 and phosphate. The multivariate logistic regression analyses showed that the adjusted risk of anemia was independently associated with higher serum phosphate and LogiFGF23 levels (ORs (95% CIs) of 4.33 (2.11–8.90) and 8.75 (3.17–24.2), respectively (p < 0.001)). A significant interaction between phosphate and iFGF23 (OR of 0.66 (0.53–0.83), p < 0.001) showed that the rise in the adjusted predicted risk of anemia with the increase in iFGF23 was steeper when phosphate levels were low. Phosphate levels acted as modifiers of the effect of iFGF23 concentration on anemia. Thus, the effect of the increase in iFGF23 levels was stronger when phosphate levels were low.
Serotype Distribution, Virulence Determinants and Antimicrobial Susceptibility of Streptococcus agalactiae Isolated from Young Infants
Authors: Jin Zhengjiang , Li Juan , Zhou Haijian , Wang Zhenhui , Yi Lu , Liu Nian , Du Jiaxi , Chang Chien-Yi , Ji Wenjing
Published: November 2022

Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is the most common cause of serious infections in the first 3 months of life worldwide. The pathogenicity of GBS is closely related to serotypes, surface proteins and virulence factors, and the distribution of them may vary temporally and geographically. However, data related to GBS surface proteins and virulence determinants in China are very few. The aim of this study is to investigate the genetic characteristics of clinical GBS isolates from infected infants. Methods: We recovered GBS isolates from infected infants younger than 3 months during 2017–2021 at Maternal and Child Health Hospital of Hubei Province in China. We assessed the GBS serotypes, surface proteins, virulence determinants and antibiotic resistance genes distribution, by Multilocus sequence typing (MLST) and whole-genome sequencing analysis. Results: Among 97 isolates (81 EOD and 16 LOD), 5 serotypes were detected. Serotype III was the most represented (49.5%), followed by type Ib (20.6%). The isolates belonged to 17 different sequence types (STs) that grouped into the 8 clonal complexes (CCs). The most frequently identified ST was ST17 (23.7%). The most predominant surface protein of alpha-protein-like (alp) family (one of the protein components of the GBS surface antigen, resistant to trypsin) present was Rib (41.2%), which was mainly detected in serotype III. The srr1, which encodes Srr1 protein, was identified in 54.6% of isolates. The hvgA encoding for hypervirulent GBS adhesin can be detected in all 24 serotype III GBS. Among the pilus islands genes, 50% and 58.8% of the isolates were positive for pi-1 and pi-2a genes, respectively. The presence of pi-2b was mainly associated with serotype III/CC17 strains; 56.7% of isolates carried tetM, tetO/tetL, ermB antibiotic resistant genes. Among all the virulence genes detected, the cfb-cylE-lmb-pavA pattern was the main virulence gene profile (81.4%), mainly in serotype III/CC17. Conclusions: The whole genomic sequencing data revealed the high variation in surface proteins, determining virulence and antibiotic resistance in clinical isolates from 97 GBS infected infants. These data provide insightful characteristics of genetic features of GBS. Constant epidemiological surveillance is warranted to provide information on the GBS pathogenic dynamics and antibiotic resistance profiles in the surveyed areas for improving therapeutic outcomes.
SARS-CoV-2 and Dengue Virus Coinfection in a Mexican Pediatric Patient: A Case Report from Early Molecular Diagnosis
Authors: Zepeda-Carrillo Eloy A. , Soria Saavedra Francisco M. , Mercado Villegas Maria B. , López Alvarado Alejandra , Regla-Nava Jose Angel , Torres-Valadez Rafael
Published: November 2022

Mexico is an endemic region for dengue virus (DENV). The increase in this disease coincides with outbreaks of COVID-19, both of which are single-stranded positive RNA viruses. These characteristics make it difficult to distinguish each disease because they share clinical and laboratory features, which can consequently result in misdiagnoses. This is why the use of precision confirmatory tests (qRT-PCR) are crucial for early diagnosis. We herein report a pediatric patient who presented a coinfection for DENV and COVID-19, “SARS-CoV-2/Dengue”. This patient initially presented a fever, cough, and headache and, three days later, developed generalized pain and epistaxis. Blood studies revealed thrombocytopenia and leukopenia, and the patient was admitted to the hospital for a probable DENV infection. Within 48 h, qRT-PCR tests specific for SARS-CoV-2 and DENV were performed and resulted as positive. The patient immediately received pharmacological treatment with azithromycin, oseltamivir, and metamizole. During hospitalization (9 days), the patient had no signs of respiratory distress and maintained normal body temperature and normal blood oxygen saturation. This case warns of the need for early diagnosis and adequate clinical and pharmacological management in the face of a “SARS-CoV-2/Dengue” coinfection. Early molecular detection of both viruses and timely treatment helped the patient to achieve a favorable recovery.
Common Microbial Genital Infections and Their Impact on the Innate Immune Response to HPV in Cervical Cells
Authors: Fracella Matteo , Oliveto Giuseppe , Sorrentino Leonardo , Roberto Piergiorgio , Cinti Lilia , Viscido Agnese , Di Lella Federica Maria , Giuffrè Federica , Gentile Massimo , Pietropaolo Valeria , Prezioso Carla , Palma Ettore , Recine Nadia , Palaia Innocenza , Scagnolari Carolina , Antonelli Guido , Pierangeli Alessandra
Published: November 2022

The persistence of high-risk (HR) human papillomavirus (HPV) genotypes is a prerequisite of cervical cancer. It is not clear whether and how bacterial vaginosis (BV) and sexually transmitted infections (STIs) cause higher rates of persistent HPV infection. This study aimed to characterize mucosal innate immunity to HPV, comparing different conditions. Specifically, expression levels of genes coding for Toll-like receptors (TLR)7 and 9, several type III Interferon-related genes (IFNL1, 2, 3, their specific receptor subunit IFNLR1, and the IFN-stimulated gene ISG15). Chemokines CCL5 and CCL20 were measured in cervical cells positive, or not, for HPV, BV, and STIs. HPV DNA was detected in 51/120 (42.5%) enrolled women, two/third were HR-HPV genotypes. More than 50% of samples were BV- and/or STI-positive. HPV-positive women had BV, but not other STIs, more frequently than the HPV-negative. TLR9 and IFNL1 mRNAs were expressed in the LR, but much less in the HR HPV infection. Enhanced levels of TLR9, TLR7, IFNL2, and IFNLR1 were observed in HPV-positive women with BV and STI. TLR9-increased expression was associated with HPV persistence in previous studies; hence, bacterial coinfections may enhance this risk. Prospective measurements of type III IFNs and IFNLR1 are warranted to evaluate whether this response may act as a double-edged sword in infected epithelia.
Copaiba Oil Resin Exerts an Additive Effect to Babassu Oil on Behavioral Changes in Human Endometriotic Cell Cultures
Authors: Silva Julianna Henriques da , Abreu Leticia Coli Louvisse de , Ferrari Renato , Quintana Celia Yelimar Palmero , Barros Eliane Gouvêa de Oliveira , Cordeiro Natália de Moraes , Pontes Bruno , Sousa Valeria Pereira de , Cabral Lucio Mendes , Fernandes Patricia Dias , Nasciutti Luiz Eurico
Published: November 2022

Background: Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu (Orbignya speciosa) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk (Copaifera langsdorffii) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC). Methods: CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. Results: After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production. Conclusions: Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.
Design, Synthesis, Molecular Modeling, and Anticancer Evaluation of New VEGFR-2 Inhibitors Based on the Indolin-2-One Scaffold
Authors: Abdelgawad Mohamed A. , Hayallah Alaa M. , Bukhari Syed Nasir Abbas , Musa Arafa , Elmowafy Mohammed , Abdel-Rahman Hamdy M. , Abd El-Gaber Mohammed K.
Published: November 2022

A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity. The effects of the most potent inhibitor, 17a, on cell cycle, apoptosis, and expression of apoptotic markers (caspase-3&-9, BAX, and Bcl-2) were studied. Molecular modeling studies, such as docking simulations, physicochemical properties prediction, and pharmacokinetic profiling were performed. The results revealed that derivatives 5b, 10e, 10g, 15a, and 17a exhibited potent anticancer activities with IC50 values from 0.74–4.62 µM against MCF-7 cell line (sunitinib IC50 = 4.77 µM) and from 1.13–8.81 µM against HepG2 cell line (sunitinib IC50 = 2.23 µM). Furthermore, these compounds displayed potent VEGFR-2 inhibitory activities with IC50 values of 0.160, 0.358, 0.087, 0.180, and 0.078 µM, respectively (sunitinib IC50 = 0.139 µM). Cell cycle analysis demonstrated the ability of 17a to induce a cell cycle arrest of the HepG2 cells at the S phase and increase the total apoptosis by 3.5-fold. Moreover, 17a upregulated the expression levels of apoptotic markers caspase-3 and -9 by 6.9-fold and 3.7-fold, respectively. In addition, 17a increased the expression level of BAX by 2.7-fold while decreasing the expression level of Bcl-2 by 1.9-fold. The molecular docking simulations displayed enhanced binding interactions and similar placement as sunitinib inside the active pocket of VEGFR-2. The molecular modeling calculations showed that all the test compounds were in accordance with Lipinski and Veber rules for oral bioavailability and had promising drug-likeness behavior.
The Effects of Positive Allosteric Modulators of α7–nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid
Authors: Gzielo Kinga , Nikiforuk Agnieszka
Published: November 2022

There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7–nicotinic acetylcholine receptors (α7–nAChRs), as a potential target of pharmacotherapy. A promising approach is based on positive allosteric modulators (PAMs) of these receptors due to their advantages over direct agonists. Nevertheless, α7 n–AChR ligands have not been widely studied in the context of autism. Therefore, using one of the most widely used rodent models of ASD, that is, prenatal exposure to valproic acid (VPA), we examined the impact of α7–nAChR PAMs (PNU–120596 and CCMI) on socio-communicative behavior during social play in adolescent male and female rats. The current study demonstrated that PAM treatment affected certain aspects of socio-communicative behavior in adolescent rats. Accordingly, PNU–120596 ameliorated deficient play abilities in VPA-exposed males, as revealed by increased play time during a social encounter. In addition, this compound enhanced the emission of ultrasonic vocalizations that accompanied playful interactions. Moreover, we observed the overall effect of PNU–120596 on non-playful forms of social behavior (i.e., social exploration) and acoustic parameters (i.e., the duration) of emitted calls. The present results suggest the ability of α7–nAChR PAMs to facilitate socio-communicative behavior in adolescent rats.
Precision Nanotoxicology in Drug Development: Current Trends and Challenges in Safety and Toxicity Implications of Customized Multifunctional Nanocarriers for Drug-Delivery Applications
Authors: Ahmad Anas , Imran Mohammad , Sharma Nisha
Published: November 2022

The dire need for the assessment of human and environmental endangerments of nanoparticulate material has motivated the formulation of novel scientific tools and techniques to detect, quantify, and characterize these nanomaterials. Several of these paradigms possess enormous possibilities for applications in many of the realms of nanotoxicology. Furthermore, in a large number of cases, the limited capabilities to assess the environmental and human toxicological outcomes of customized and tailored multifunctional nanoparticles used for drug delivery have hindered their full exploitation in preclinical and clinical settings. With the ever-compounded availability of nanoparticulate materials in commercialized settings, an ever-arising popular debate has been egressing on whether the social, human, and environmental costs associated with the risks of nanomaterials outweigh their profits. Here we briefly review the various health, pharmaceutical, and regulatory aspects of nanotoxicology of engineered multifunctional nanoparticles in vitro and in vivo. Several aspects and issues encountered during the safety and toxicity assessments of these drug-delivery nanocarriers have also been summarized. Furthermore, recent trends implicated in the nanotoxicological evaluations of nanoparticulate matter in vitro and in vivo have also been discussed. Due to the absence of robust and rigid regulatory guidelines, researchers currently frequently encounter a larger number of challenges in the toxicology assessment of nanocarriers, which have also been briefly discussed here. Nanotoxicology has an appreciable and significant part in the clinical translational development as well as commercialization potential of nanocarriers; hence these aspects have also been touched upon. Finally, a brief overview has been provided regarding some of the nanocarrier-based medicines that are currently undergoing clinical trials, and some of those which have recently been commercialized and are available for patients. It is expected that this review will instigate an appreciable interest in the research community working in the arena of pharmaceutical drug development and nanoformulation-based drug delivery.
AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats
Authors: Yan Weidong , Gao Sizhe , Zhang Qiaoni , Qi Jiachen , Liu Gang , Teng Yuan , Wang Jian , Yan Shujie , Ji Bingyang
Published: November 2022

Deep hypothermic circulatory arrest (DHCA) can induce systemic inflammatory response syndrome, including neuroinflammation. Finding suitable compounds is necessary for attenuating neuroinflammation and avoiding cerebral complications following DHCA. In the present study, we established DHCA rat models and monitored the vital signs during the surgical process. After surgery, we found significantly increased proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in DHCA rats. Quantitative proteomics analysis was performed for exploring the differentially expressed proteins in hippocampus of DHCA rats and the data showed the adiponectin receptor 1 protein was upregulated. More importantly, administration of AdipoRon, a small-molecule adiponectin receptor agonist, could improve the basic vital signs and attenuate the increased IL-6, IL-1β, and TNF-α in DHCA rats. Furthermore, AdipoRon inhibits the activation of microglia (M1 state) and promotes their transition to an anti-inflammatory state, via promoting the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), and downregulating nuclear factor kappa B (NF-κB) in DHCA rats. Consistently, we used LPS-treated BV2 cells to mimic the neuroinflammatory condition and found that AdipoRon dose-dependently decreased cytokines, along with increased phosphorylation of AMPK and downregulated NF-κB. In conclusion, our present data supported that AdipoRon inhibited DHCA-induced neuroinflammation via activating the hippocampal AMPK/NF-κB pathway.
Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC
Authors: Scarabel Lucia , Bignucolo Alessia , Toffoli Giuseppe , Cecchin Erika , De Mattia Elena
Published: November 2022

Pharmacogenetics plays a key role in personalized cancer treatment. Currently, the clinically available pharmacogenetic markers for metastatic colorectal cancer (mCRC) are in genes related to drug metabolism, such as DPYD for fluoropyrimidines and UGT1A1 for irinotecan. Recently, the impact of host variability in inflammatory and immune-response genes on treatment response has gained considerable attention, opening innovative perspectives for optimizing tailored mCRC therapy. A literature review was performed on the predictive role of immune-related germline genetic biomarkers on pharmacological outcomes in patients with mCRC. Particularly, that for efficacy and toxicity was reported and the potential role for clinical management of patients was discussed. Most of the available data regard therapy effectiveness, while the impact on toxicity remains limited. Several studies focused on the effects of polymorphisms in genes related to antibody-dependent cellular cytotoxicity (FCGR2A, FCGR3A) and yielded promising but inconclusive results on cetuximab efficacy. The remaining published data are sparse and mainly hypothesis-generating but suggest potentially interesting topics for future pharmacogenetic studies, including innovative gene–drug interactions in a clinical context. Besides the tumor immune escape pathway, genetic markers belonging to cytokines/interleukins (IL-8 and its receptors) and angiogenic mediators (IGF1) seem to be the best investigated and hopefully most promising to be translated into clinical practice after validation.
Anti-Candida Activity of Extracts Containing Ellagitannins, Triterpenes and Flavonoids of Terminalia brownii, a Medicinal Plant Growing in Semi-Arid and Savannah Woodland in Sudan
Authors: Salih Enass Y. A. , Julkunen-Tiitto Riitta , Luukkanen Olavi , Fyhrqvist Pia
Published: November 2022

Various parts of Terminalia brownii (Fresen) are used in Sudanese traditional medicine against fungal infections. The present study aimed to verify these uses by investigating the anti-Candida activity and phytochemistry of T. brownii extracts. Established agar diffusion and microplate dilution methods were used for the antifungal screenings. HPLC-DAD and UHPLC/QTOF-MS were used for the chemical fingerprinting of extracts and for determination of molecular masses. Large inhibition zones and MIC values of 312 µg/mL were obtained with acetone, ethyl acetate and methanol extracts of the leaves and acetone and methanol extracts of the roots. In addition, decoctions and macerations of the leaves and stem bark showed good activity. Sixty compounds were identified from a leaf ethyl acetate extract, showing good antifungal activity. Di-, tri- and tetra-gallotannins, chebulinic acid (eutannin) and ellagitannins, including an isomer of methyl-(S)-flavogallonate, terflavin B and corilagin, were detected in T. brownii leaves for the first time. In addition, genipin, luteolin-7-O-glucoside, apigenin, kaempferol-4’-sulfate, myricetin-3-rhamnoside and sericic acid were also characterized. Amongst the pure compounds present in T. brownii leaves, apigenin and β-sitosterol gave the strongest growth inhibitory effects. From this study, it was evident that the leaf extracts of T. brownii have considerable anti-Candida activity with MIC values ranging from 312 to 2500 µg/mL.