bluuebunny/crossref_metadata_2025 huggingface dataset:
The Superiority of Bacillus megaterium over Escherichia coli as a Recombinant Bacterial Host for Hyaluronic Acid Production
Authors: Nasser HebaT’Allah , Eikmanns Bernhard J. , Tolba Mahmoud M. , El-Azizi Mohamed , Abou-Aisha Khaled
Published: November 2022

(1) Background: Hyaluronic acid (HA) is a polyanionic mucopolysaccharide extensively used in biomedical and cosmetic industries due to its unique rheological properties. Recombinant HA production using other microbial platforms has received increasing interest to avoid potential toxin contamination associated with its production by streptococcal fermentation. In this study, the Gram-negative strains Escherichia coli (pLysY/Iq), E. coli Rosetta2, E. coli Rosetta (DE3) pLysS, E. coli Rosetta2 (DE3), E. coli Rosetta gammiB(DE3)pLysS, and the Gram-positive Bacillus megaterium (MS941) were investigated as new platforms for the heterologous production of HA. (2) Results: The HA biosynthesis gene hasA, cloned from Streptococcus equi subsp. zoopedemicus, was ligated into plasmid pMM1522 (MoBiTec), resulting in pMM1522 hasA, which was introduced into E. coli Rosetta-2(DE3) and B. megaterium (MS941). The initial HA titer by the two hosts in the LB medium was 5 mg/L and 50 mg/L, respectively. Streptococcal hasABC and hasABCDE genes were ligated into plasmid pPT7 (MoBiTec) and different E. coli host strains were then transformed with the resulting plasmids pPT7hasABC and pPT7hasABCDE. For E. coli Rosetta-gamiB(DE3)pLysS transformed with pPT7hasABC, HA production was 500 ± 11.4 mg/L in terrific broth (TB) medium. Productivity was slightly higher (585 ± 2.9 mg/L) when the same host was transformed with pPT7 carrying the entire HA operon. We also transformed B. megaterium (MS941) protoplasts carrying T7-RNAP with pPT7hasABC and pPT7hasABCDE. In comparison, the former plasmid resulted in HA titers of 2116.7 ± 44 and 1988.3 ± 19.6 mg/L in LB media supplemented with 5% sucrose and A5 medium + MOPSO, respectively; the latter plasmid boosted the titer final concentration further to reach 2476.7 ± 14.5 mg/L and 2350 ± 28.8 mg/L in the two media, respectively. The molecular mass of representative HA samples ranged from 105 − 106 Daltons (Da), and the polydispersity index (PDI) was <2. Fourier transform infrared spectroscopy (FTIR) spectra of the HA product were identical to those obtained for commercially available standard polymers. Finally, scanning electron microscopic examination revealed the presence of extensive HA capsules in E. coli Rosetta-gamiB(DE3)pLysS, while no HA capsules were produced by B. megaterium. (3) Conclusions: Our results suggested that Gram-positive bacteria are probably superior host strains for recombinant HA production over their Gram-negative counters. The titers and the molecular weight (MW) of HA produced by B. megaterium were significantly higher than those obtained by different E. coli host strains used in this study.
Development of a Real-Time Recombinase-Aided Amplification Method to Rapidly Detect Methicillin-Resistant Staphylococcus aureus
Authors: Ding Xiaoyan , Wang Hejia , Cui Mingquan , Cheng Min , Zhao Qi , Bai Yuhui , Zhang Chunping , Zhang Cunshuai , Xu Shixin , Li Ting
Published: November 2022

Methicillin-resistant staphylococcus aureus (MRSA) is a major pathogen responsible for human hospital and community-onset diseases and severe invasive livestock infections. Rapid detection of MRSA is essential to control the spread of MRSA. Conventional identification methods and antibacterial susceptibility tests of MRSA are time-consuming. The commonly used qPCR assay also has the disadvantages of being complicated and expensive, restricting its application in resource-limited clinical laboratories. Here, a real-time fluorescent recombinase-assisted amplification (RAA) assay targeting the most conserved regions within the mecA gene of MRSA was developed and evaluated to detect MRSA. The detection limit of this assay was determined to be 10 copies/reaction of positive plasmids. The established RAA assay showed high specificity for MRSA detection without cross-reactivities with other clinically relevant bacteria. The diagnostic performance of real-time RAA was evaluated using 67 clinical S. aureus isolates from dairy farms, which were detected in parallel using the TaqMan probe qPCR assay. The results showed that 56 and 54 samples tested positive for MRSA by RAA and qPCR, respectively. The overall agreement between both assays was 97.01% (65/67), with a kappa value of 0.9517 (p < 0.001). Further linear regression analysis demonstrated that the detection results between the two assays were significantly correlated (R2 = 0.9012, p < 0.0001), indicating that this RAA assay possesses similar detection performance to the qPCR assay. In conclusion, our newly established RAA assay is a time-saving and convenient diagnostic tool suitable for MRSA detection and screening.
Revisiting Limestone Quality for Soil Liming Purpose
Authors: Bortoluzzi Edson Campanhola , Garibotti Andressa , Tiecher Tales , dos Santos Danilo Rheinheimer , Moterle Diovane Freire , Fiorin Jackson E.
Published: November 2022

The quality of lime is generally estimated by traditional methodologies, which consist of coarse granulometry and chemical reactivity determinations. Performing a detailed chemical/mineralogical and fine granulometric characterization is the objective of this study. Fifteen lime samples, from an original 52 commercial samples, were analyzed by their granulometric profile (GP) and chemical-mineralogical compositions to discuss limestone quality inside the tree group of traditional efficiency neutralizing power (ENP) and Mg contents. The lime reactivity was estimated using laser diffraction under water and acid solution (1 mol L−1 HCl). The grain-size distribution ranged from 0.563 to 1124 µm and the GP was associated with the chemical and mineralogical compositions. Samples with high ENP (>99%) presented differences in GP regarding Mg contents. Lime with low ENP presents the most varied mineral assemblage, while calcite and dolomite were the predominant minerals in high-ENP samples. Samples containing high Mg were the most sensitive to the acid solution, suggesting great reactivity. This work contributes to a better understanding of limestone quality than routine analyses performed so far. Additionally, the use of the laser diffraction method promotes a rapid lime reactivity test for liming purposes.
Prediction of Slag Viscosity Based on Machine Learning for Molten Gasification of Hazardous Wastes
Authors: Li Changlun , Xi Wenshuai , Wang Caihong , Lin Xiongchao , Xu Deping , Wang Yonggang
Published: November 2022

Experimental data from viscosity measurements of 124 glassy slags were used to drive and develop machine learning models that could be used for direct or indirect viscosity prediction. Samples were categorized according to the content of chemical components or general competitive neural network. The direct viscosity prediction using artificial neural network models of different kinds of slag samples was established. The prediction average error and maximum absolute error in the corresponding models were significantly smaller than the artificial neural network without categorizing the samples. Moreover, the viscosity curve for each glassy slag was fitted by a general formula, and the corresponding parameters were obtained. The principal component analysis (PCA)–particle swarm optimization (PSO)–back propagation (BP) neural network models for predicting parameters were proposed. This indirect approach was considered to successfully overcome the limitations of temperature and viscosity ranges in direct prediction while delivering smooth viscosity curves.
Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study
Authors: Euden Joanne , Pallmann Philip , Grozeva Detelina , Albur Mahableshwar , Bond Stuart E. , Brookes-Howell Lucy , Dark Paul , Hellyer Thomas , Hopkins Susan , Howard Philip , Llewelyn Martin J. , Maboshe Wakunyambo , McCullagh Iain J. , Ogden Margaret , Parsons Helena , Partridge David , Powell Neil , Shaw Dominick , Shinkins Bethany , Szakmany Tamas , Todd Stacy , Thomas-Jones Emma , West Robert M. , Carrol Enitan D. , Sandoe Jonathan A. T.
Published: November 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.
Inhibitors and Enablers to Explainable AI Success: A Systematic Examination of Explanation Complexity and Individual Characteristics
Authors: Wienrich Carolin , Carolus Astrid , Roth-Isigkeit David , Hotho Andreas
Published: November 2022

With the increasing adaptability and complexity of advisory artificial intelligence (AI)-based agents, the topics of explainable AI and human-centered AI are moving close together. Variations in the explanation itself have been widely studied, with some contradictory results. These could be due to users’ individual differences, which have rarely been systematically studied regarding their inhibiting or enabling effect on the fulfillment of explanation objectives (such as trust, understanding, or workload). This paper aims to shed light on the significance of human dimensions (gender, age, trust disposition, need for cognition, affinity for technology, self-efficacy, attitudes, and mind attribution) as well as their interplay with different explanation modes (no, simple, or complex explanation). Participants played the game Deal or No Deal while interacting with an AI-based agent. The agent gave advice to the participants on whether they should accept or reject the deals offered to them. As expected, giving an explanation had a positive influence on the explanation objectives. However, the users’ individual characteristics particularly reinforced the fulfillment of the objectives. The strongest predictor of objective fulfillment was the degree of attribution of human characteristics. The more human characteristics were attributed, the more trust was placed in the agent, advice was more likely to be accepted and understood, and important needs were satisfied during the interaction. Thus, the current work contributes to a better understanding of the design of explanations of an AI-based agent system that takes into account individual characteristics and meets the demand for both explainable and human-centered agent systems.
Associations of Dietary Intakes with Gynecological Cancers: Findings from a Cross-Sectional Study
Authors: Zhu Guixian , Li Zengbin , Tang Liqiong , Shen Mingwang , Zhou Zhangjian , Wei Yuhang , Zhao Yang , Bai Shuheng , Song Lingqin
Published: November 2022

Background: Gynecological cancers, including cervical cancer, ovarian cancer and endometrial cancer are leading causes of cancer-related death in women worldwide. Diet plays an important role in cancer development, which is widely accepted. However, the associations between dietary intakes and gynecological cancers remain unclear. Methods: A total of 12,437 women aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007–2016, were included in this study. The relationships between 30 dietary factors (4 macronutrients, 15 vitamins, 9 minerals, caffeine and alcohol) and gynecological cancers were assessed. Results: We observed negative correlations of intakes of phosphorus (odds ratio (OR), 95% confidence interval (CI); 0.998 (0.996, 0.999), p = 0.002) with cervical cancer, and intakes of vitamin B12 (0.812 (0.714, 0.925), p = 0.002), phosphorus (0.997 (0.996, 0.999), p < 0.001) and alcohol (0.971 (0.950, 0.992), p = 0.009) with endometrial cancer. The data showed positive associations of intake of caffeine (1.002 (1.001, 1.003), p = 0.003) with cervical cancer, and intake of copper (2.754 (1.313, 5.778), p = 0.009) with endometrial cancer. In addition, we found potential negative correlations between intake of vitamin B1 (p = 0.025) and cervical cancer; zinc (p = 0.048) and ovarian cancer; and potassium (p = 0.032) and endometrial cancer. Potential positive associations were found between intake of calcium and cervical cancer (p = 0.026) and endometrial cancer (p = 0.034), and between sodium (p = 0.042) and endometrial cancer. Intakes of protein, total sugars, total fat, cholesterol, vitamin A, alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, vitamin B2, niacin, vitamin B6, food folate, vitamin C, vitamin D, vitamin E, vitamin K, magnesium, iron and selenium showed no relationship with gynecological cancers (p > 0.05). Conclusions: Specific dietary factors were associated with gynecological cancers. More epidemiological studies are needed to validate our results.
Benefits of Circulating Human Metabolites from Fish Cartilage Hydrolysate on Primary Human Dermal Fibroblasts, an Ex Vivo Clinical Investigation for Skin Health Applications
Authors: Wauquier Fabien , Boutin-Wittrant Line , Bouvret Elodie , Le Faouder Julie , Roux Véronique , Macian Nicolas , Pickering Gisèle , Wittrant Yohann
Published: November 2022

Due to its significant exposure to stressful environmental factors, the skin undergoes a high remodeling rate over time, which alters not only its appearance but also its functionality. This alteration of the skin, namely photoaging, is characterized by dryness and a loss of elasticity that mainly originates from the dysregulation of dermal fibroblast activities. In order to overcome such tissue outcome, cosmetic products have evolved toward nutricosmetics, thus promoting beauty from within. Among bio-actives of interest, bio-peptides deriving from plant or animal sources may exert various biological activities beyond their nutritional value. However, studies remain mostly descriptive and the mode of action at the cellular level in clinic remains a concern. In a recent clinical trial, it was showed that supplementation with a fish cartilage hydrolysate (FCH) improved signs of chronological and photoaging-induced skin changes in healthy women. Here, using an original ex vivo clinical approach adapted to nutricosmetic purpose, we further demonstrated that this fish cartilage hydrolysate was absorbed and that the circulating metabolites produced in humans following FCH intake stimulate human dermal fibroblast growth, promote specific hyaluronan production, up-regulate elastin synthesis and inhibit MMP-1 and 3 expression along with the enhancement of TGF-β release. Altogether, these data provide clues on the mechanisms likely contributing to the beneficial impact of FCH on human skin functionality by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging onset.
Associations of Genetically Predicted Vitamin B12 Status across the Phenome
Authors: Dib Marie-Joe , Ahmadi Kourosh R. , Zagkos Loukas , Gill Dipender , Morris Brooke , Elliott Paul , Dehghan Abbas , Tzoulaki Ioanna
Published: November 2022

Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20–0.50) and pernicious anaemia (0.29, 0.19–0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.
On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
Authors: Duntas Leonidas H. , Alexandraki Krystallenia I.
Published: November 2022

The 100th anniversary of the discovery of vitamin D3 (VitD3) coincides with significant recent advances in understanding its mechanism of action along with accumulating knowledge concerning its genomic and nongenomic activities. A close relationship between VitD3 and the immune system, including both types of immunity, innate and adaptive, has been newly identified, while low levels of VitD3 have been implicated in the development of autoimmune thyroiditis (AIT). Active 1,25(OH)2 D3 is generated in immune cells via 1-α-hydroxylase, subsequently interacting with the VitD3 receptor to promote transcriptional and epigenomic responses in the same or adjacent cells. Despite considerable progress in deciphering the role of VitD3 in autoimmunity, its exact pathogenetic involvement remains to be elucidated. Finally, in the era of coronavirus disease 2019 (COVID-19), brief mention is made of the possible links between VitD3 deficiency and risks for severe COVID-19 disease. This review aims to commemorate the centennial of the discovery of VitD3 by updating our understanding of this important nutrient and by drawing up a framework of guidance for VitD3 supplementation, while emphasizing the necessity for personalized treatment in patients with autoimmune thyroid disease. A tailored approach based on the specific mechanisms underlying VitD3 deficiency in different diseases is recommended.
Early Enteral Feeding of the Preterm Infant—Delay until Own Mother’s Breastmilk Becomes Available? (Israel, 2012–2017)
Authors: Ofek Shlomai Noa , Patt Yonatan Shneor , Wazana Yaara , Ziv-Baran Tomer , Strauss Tzipora , Morag Iris
Published: November 2022

Aim: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother’s breastmilk or to wait for breastmilk to be available. Methods: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012–2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported. Results: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group. Conclusion: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother’s breastmilk.
Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research
Authors: Amimo Joshua O. , Michael Husheem , Chepngeno Juliet , Raev Sergei A. , Saif Linda J. , Vlasova Anastasia N.
Published: November 2022

Vitamin A (VA) is critical for many biological processes, including embryonic development, hormone production and function, the maintenance and modulation of immunity, and the homeostasis of epithelium and mucosa. Specifically, VA affects cell integrity, cytokine production, innate immune cell activation, antigen presentation, and lymphocyte trafficking to mucosal surfaces. VA also has been reported to influence the gut microbiota composition and diversity. Consequently, VA deficiency (VAD) results in the imbalanced production of inflammatory and immunomodulatory cytokines, intestinal inflammation, weakened mucosal barrier functions, reduced reactive oxygen species (ROS) and disruption of the gut microbiome. Although VAD is primarily known to cause xerophthalmia, its role in the impairment of anti-infectious defense mechanisms is less defined. Infectious diseases lead to temporary anorexia and lower dietary intake; furthermore, they adversely affect VA status by interfering with VA absorption, utilization and excretion. Thus, there is a tri-directional relationship between VAD, immune response and infections, as VAD affects immune response and predisposes the host to infection, and infection decreases the intestinal absorption of the VA, thereby contributing to secondary VAD development. This has been demonstrated using nutritional and clinical studies, radiotracer studies and knockout animal models. An in-depth understanding of the relationship between VAD, immune response, gut microbiota and infections is critical for optimizing vaccine efficacy and the development of effective immunization programs for countries with high prevalence of VAD. Therefore, in this review, we have comprehensively summarized the existing knowledge regarding VAD impacts on immune responses to infections and post vaccination. We have detailed pathological conditions associated with clinical and subclinical VAD, gut microbiome adaptation to VAD and VAD effects on the immune responses to infection and vaccines.
A Breastfeeding Relaxation Intervention Promotes Growth in Late Preterm and Early Term Infants: Results from a Randomized Controlled Trial
Authors: Dib Sarah , Wells Jonathan C. K. , Eaton Simon , Fewtrell Mary
Published: November 2022

Breastfeeding involves signaling between mother and offspring through biological (breast milk) and behavioral pathways. This study tested this by examining the effects of a relaxation intervention in an understudied infant population. Breastfeeding mothers of late preterm (340/7–366/7 weeks) and early term (370/7–386/7 weeks) infants were randomized to the relaxation group (RG, n = 35), where they were asked to listen to a meditation recording while breastfeeding from 3 weeks post-delivery, or the control group (CG, n = 37) where no intervention was given. Primary outcomes-maternal stress and infant weight-were assessed at 2–3 (baseline) and 6–8 weeks post-delivery. Secondary outcomes included infant length, infant behavior, maternal verbal memory, salivary cortisol, and breast milk composition. Infants in the RG had significantly higher change in weight-for-age Z-score compared to those in CG (effect size: 0.4; 95% CI: 0.09, 0.71; p = 0.01), and shorter crying duration [RG: 5.0 min, 0.0–120.0 vs. CG: 30.0 min, 0.0–142.0; p = 0.03]. RG mothers had greater reduction in cortisol (effect size: −0.08 ug/dL, 95% CI −0.15, −0.01; p = 0.03) and better maternal verbal learning score (effect size: 1.1 words, 95% CI 0.04, 2.1; p = 0.04) than CG mothers, but did not differ in stress scores. A simple relaxation intervention during breastfeeding could be beneficial in promoting growth of late preterm and early term infants. Further investigation of other potential biological and behavioral mediators is warranted.
Muscle Function, Body Composition, Insulin Sensitivity and Physical Activity in Adolescents Born Preterm: Impact of Gestation and Vitamin D Status
Authors: Wood Claire L. , Tinnion Robert , Hollingsworth Kieren G. , Trenell Michael I. , Pearce Mark S. , Cheetham Tim D. , Embleton Nicholas D.
Published: November 2022

Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1–18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact on muscle metabolism.
Adzuki Bean MY59 Extract Reduces Insulin Resistance and Hepatic Steatosis in High-Fat-Fed Mice via the Downregulation of Lipocalin-2
Authors: Lee Jaewoong , Lee Byong Won , Kim Kyung Eun , An Hyeong Seok , Jeong Eun Ae , Shin Hyun Joo , Song Seok Bo , Roh Gu Seob
Published: November 2022

Adzuki bean is well known as a potential functional food that improves metabolic complications from obesity and diabetes. Lipocalin-2 (LCN2) has been implicated to have an important role in obesity and diabetes. However, the protective roles of adzuki bean MY59 extract (ABE) on insulin resistance and hepatic steatosis are not fully understood. In the present study, we investigated the effects of ABE on LCN2 expression in high-fat diet (HFD)-fed mice. ABE reduced HFD-induced fat mass and improved insulin resistance. In addition to hepatic steatosis, HFD-fed mice showed many apoptotic cells and neutrophils in the epididymal fat pads. However, these findings were significantly reduced by ABE supplementation. In particular, we found that increased LCN2 proteins from serum, epididymal fat pads, and liver in HFD-fed mice are significantly reduced by ABE. Furthermore, ABE reduced increased heme oxygenase-1 and superoxide dismutase-1 expressions in adipose tissue and liver in HFD-fed mice. We found that hepatic nuclear factor-kappa B (NF-κB) p65 expression in HFD-fed mice was also reduced by ABE. Thus, these findings indicate that ABE feeding could improve insulin resistance and hepatic steatosis by decreasing LCN2-mediated inflammation and oxidative stress in HFD-fed mice.
Genetic Predisposition, Fruit Intake and Incident Stroke: A Prospective Chinese Cohort Study
Authors: Wang Jun , Li Jianxin , Liu Fangchao , Huang Keyong , Yang Xueli , Liu Xiaoqing , Cao Jie , Chen Shufeng , Shen Chong , Yu Ling , Lu Fanghong , Zhao Liancheng , Li Ying , Hu Dongsheng , Huang Jianfeng , Gu Dongfeng , Lu Xiangfeng
Published: November 2022

The aim of this study was to evaluate the association between fruit intake and stroke risk considering the genetic predisposition. We used data from 34,871 participants from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR project) from 2007 to 2020. A polygenic risk score comprising 534 genetic variants associated with stroke and its related factors was constructed to categorize individuals into low, intermediate, and high genetic risk groups. The associations of genetic and fruit intake with incident stroke were assessed by the Cox proportional hazard regression. We documented 2586 incident strokes during a median follow-up of 11.2 years. Compared with fruit intake < 200 g/week, similar relative risk reductions in stroke with adherence to fruit intake > 100 g/day across the genetic risk categories were observed (28–32%), but the absolute risk reductions were relatively larger in the highest genetic risk group (p for trend = 0.03). In comparison to those with a fruit intake < 200 g/week, those with a fruit intake >100 g/day in the low, intermediate, and high genetic risk groups had an average of 1.45 (95% CI, 0.61–2.31), 2.12 (1.63–2.59), and 2.19 (1.13–3.22) additional stroke-free years at aged 35, respectively. Our findings suggest that individuals with a high genetic risk could gain more absolute risk reductions and stroke-free years than those with a low genetic risk from increasing fruit intake for the stroke primary prevention.
Effect of Fortified Formula on Growth and Nutritional Status in Young Children: A Systematic Review and Meta-Analysis
Authors: Brooker Paige G. , Rebuli Megan A. , Williams Gemma , Muhlhausler Beverly S.
Published: November 2022

Previous reviews of the effect of young child formulas on health outcomes in infants and toddlers have been inconclusive. In this study, we undertook a contemporary synthesis of studies investigating the effects of consuming fortified milk beverages (compared to cow’s milk or unfortified comparator formula) on growth and/or nutritional status in children 1–3 years of age. Five electronic databases were searched (PubMed, Web of Science, Scopus, ProQuest, and Cochrane Library) for randomised controlled trials comparing fortified milk against control milk in young children (9–48 months), published between January 1990 and June 2022. Outcomes were growth, body composition, biochemical markers, and/or nutritional status. Mean differences (MD) were pooled using random-effects meta-analysis where there were ≥3 studies. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Nineteen articles (12 studies; n = 4795) met the inclusion criteria. Heterogeneity was substantial, likely attributable to considerable variation in study characteristics. Fortified milk was associated with increased weight gain (MD = 0.14 kg [95% CI 0.06, 021], p = 0.0003) compared with control milk. Subgroup analyses demonstrated increases in weight in lower-income countries, and in studies with intervention periods > 6 months. There were no effects of fortified milks on other anthropometric measures. Haemoglobin (MD = 3.76 g/L [95% CI 0.17, 7.34], p = 0.04) and ferritin (MD = 0.01 nmol/L [95% CI 0.00, 0.02], p = 0.02) concentrations were increased in infants consuming fortified milks. Fortified milk beverages appear to offer a safe and acceptable source of complementary nutrition as a short-term strategy for addressing nutritional deficits and may modestly promote weight gain in vulnerable populations when provided for periods > 6 months. This study was prospectively registered with PROSPERO (CRD42022339920) and funded by the Infant Nutrition Council.
Anti-Inflammatory Dietary Diversity and Depressive Symptoms among Older Adults: A Nationwide Cross-Sectional Analysis
Authors: Lv Xiaoyang , Sun Siwei , Wang Jingjing , Chen Huashuai , Li Shaojie , Hu Yang , Yu Mingzhi , Zeng Yi , Gao Xiangyang , Xu Yajun , Yao Yao
Published: November 2022

The purpose of this study was to associate the anti-inflammatory dietary diversity and depressive symptoms among a nationwide sample of Chinese older adults. We used data from the 2018 wave of Chinese longitudinal healthy longevity survey (CLHLS). We assessed depressive symptoms using the 10 items of the center for epidemiologic studies depression scale (CES-D-10). Based on the dietary diversity index (DDI) generated by previous studies, we construct two novel indicators: the protein-enriched dietary diversity index diet (PEDDI) and the anti-inflammatory dietary diversity index diet (AIDDI). We used multivariate logistic models to evaluate the associations of DDI, PEDDI, and AIDDI with depressive symptoms, statistically adjusted for a range of potential confounders. A total of 12,192 participants (mean age 83.6 years) were included in the analysis. We found that participants with a higher score of DDI (OR = 0.91, 95% CI: 0.89–0.92) and PEDDI (OR = 0.91, 95% CI: 0.88–0.93) showed lower odds of having depressive symptoms, while the association between AIDDI and depressive symptoms was more marked (OR = 0.80, 95% CI: 0.78–0.83). The associations remained in subgroup analyses and sensitivity analyses. The results indicate that intaking diversified diet, particularly anti-inflammatory foods, may be associated with a lower risk of depressive symptoms. The findings of this study, if confirmed as causal, provide evidence that an intervention of adopting an anti-inflammatory diversified diet may reduce the burden of depression among older adults.
Pharmacodynamics and Clinical Implications of the Main Bioactive Peptides: A Review
Authors: Colletti Alessandro , Favari Elda , Grandi Elisa , Cicero Arrigo F. G.
Published: November 2022

Bioactive peptides (BPs) are a heterogeneous class of molecules found in a wide range of plant and animal sources. BPs have a number of different industrial applications including pharmacology (nutraceuticals), food, cosmetology, and pet food. Though BPs were initially used mainly as food additives, today the estimated peptide-based product market is around US $40 billion per year, highlighting consumer demand. The nutraceutical field is one of the most interesting applications for BPs, however there are some limitations to the efficacy of BPs in nutraceutical treatments, including low bioaccessibility and bioavailability. Thus, new extraction and isolation techniques have been developed, using both vegetable and animal sources, to obtain BPs with specific activities and improve the bioactivity and the bioavailability. Randomized clinical trials show a possible relationship between the administration of BPs and the reduction of several cardiovascular risk factors, including hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycaemia. In addition, BPs exhibit antioxidant, anti-inflammatory, antimicrobial, and anticancer potential, but long-term clinical studies are still needed. The aim of this review is to give a general introduction of BPs, describe their production and application methods, present data regarding bioactivity and bioavailability, and finally highlight the future prospects of this class of molecules in clinical practice.
Mirabegron and Physical Exercise Is a Potential Strategical for BAT Activation in Obesity
Authors: Antunes Gabriel Calheiros , Macêdo Ana Paula Azevêdo , Conceição Luciana Renata , Pauli José Rodrigo
Published: November 2022

(1) Background: Obesity is a global epidemic issue that has increased greatly in recent decades. Although interventions such as nutritional approaches and the practice of physical exercise are potential therapies to combat obesity, in some cases they are not sufficient. Therefore, the development of new pharmacological treatments is necessary. Combining these therapies with non-pharmacological alternatives could be an interesting strategy for treating obesity. Considered a pharmacological treatment for overactive bladder (OAB), mirabegron is also categorized as a β(3)-adrenoceptor agonist, and is used in recommended doses of 25 mg and 50 mg. Animal models have shown that the administration of 0.8 mg/kg of mirabegron leads to elevated activation of brown adipose tissue (BAT) and white adipose tissue (WAT) browning. (2) Results: Findings suggest that the pharmacological application of mirabegron has numerous beneficial effects in lipid metabolism, suggesting a potential action against obesity. In this context, physical exercise and mirabegron stimulate browning activation using different mechanisms. (3) Conclusions: According to the results of the studies presented in this review, mirabegron may be a promising pharmacological treatment for obesity due to its significant effects on estimated energy expenditure (EER) through thermogenesis elevation, BAT activation, and WAT browning seen in dosages up to 100 mg. In addition, the administration of mirabegron combined with physical exercise may be a potential alternative for increasing the body’s energy expenditure, with actions in distinct signaling pathways. Thus, physical exercise combined with mirabegron can alleviate some adverse side effects encountered with the use of the medication. Finally, although there have been advances in knowledge, more studies are needed to understand the combined effects of using mirabegron and physical exercise.
A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani
Authors: Hayat Obaid , Ullah Nazif , Sirajuddin Muhammad , Giardini Miriam A. , Nguyen Jennifer V. , Francisco Karol R. , Liu Lawrence J. , Sun Yujie Uli , Maurya Svetlana , McGrosso Dominic , Gonzalez David J. , Caffrey Conor R. , Debnath Anjan , Siqueira-Neto Jair L.
Published: November 2022

Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In this context, we tested the antiparasitic potential of 10 organotin (IV) derivatives from 4-(4-methoxyphenylamino)-4 oxobutanoic acid (MS26) against seven eukaryotic pathogens of medical importance: Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Giardia lamblia, Naegleria fowleri and Schistosoma mansoni. Among the compounds with and without antiparasitic activity, compound MS26Et3 stood out with a 50% effective concentration (EC50) of 0.21 and 0.19 µM against promastigotes and intracellular amastigotes of L. donovani, respectively, 0.24 µM against intracellular amastigotes of T. cruzi, 0.09 µM against T. brucei, 1.4 µM against N. fowleri and impaired adult S. mansoni viability at 1.25 µM. In terms of host/pathogen selectivity, MS26Et3 demonstrated relatively mild cytotoxicity toward host cells with a 50% viability concentration of 4.87 µM against B10R cells (mouse monocyte cell line), 2.79 µM against C2C12 cells (mouse myoblast cell line) and 1.24 µM against HEK923 cells (human embryonic kidney cell line). The selectivity index supports this molecule as a therapeutic starting point for a broad spectrum antiparasitic alternative. Proteomic analysis of host cells infected with L. donovani after exposure to MS26Et3 showed a reduced expression of Rab7, which may affect the fusion of the endosome with the lysosome, and, consequently, impairing the differentiation of L. donovani to the amastigote form. Future studies to investigate the molecular target(s) and mechanism of action of MS26Et3 will support its chemical optimization.
First Evidence of the Presence of the Causative Agent of Caseous Lymphadenitis—Corynebacterium pseudotuberculosis in Dairy Products Produced from the Milk of Small Ruminants
Authors: Langova Denisa , Slana Iva , Okunkova Jana , Moravkova Monika , Florianova Martina , Markova Jirina
Published: November 2022

This study focused on the detection and quantification of selected bacteria and on the presence of enterotoxin genes in milk and dairy products from sheep and goat farms in the Czech Republic using quantitative real-time PCR (qPCR) and multiplex PCR (PCR). The presence of Corynebacterium pseudotuberculosis (CP), Mycobacterium avium subsp. paratuberculosis (MAP), Listeria monocytogenes, Staphylococcus aureus, S. aureus enterotoxin genes and methicillin-resistant Staphylococcus aureus (MRSA) was determined in 18 milk samples, 28 fresh cheeses, 20 ripened cheeses and 14 yoghurts. The serological status of the herds in relation to CP and MAP was taken into account. The most frequently detected bacterium was S. aureus (48.8%), and subsequent PCR revealed 11 MRSA positive samples. The S. aureus enterotoxin genes seg, sei and sec were detected in two goat cheeses. Cheese samples showed a statistically higher risk of SA and MRSA occurrence. CP (8.8%) and MAP (13.8%) were detected by qPCR on two different seropositive farms. Cultivation of qPCR positive CP samples on agar plates supplemented with potassium tellurite showed the presence of viable bacterium. The results obtained confirmed the necessity of monitoring the infectious status of dairy animals and rapid diagnosis of bacterial pathogens in milk and dairy products.
Methicillin-Resistant Staphylococcus aureus Membrane Vesicles Inhibit the Proliferation and Induce the Apoptosis of Epithelial Cells
Authors: Chen Xu , Zhang Jingwei , Yang Meng , Du Guanhuan , Chen Fuxiang
Published: November 2022

Staphylococcus aureus, or methicillin-resistant Staphylococcus aureus (MRSA), is the predominant pathogen in skin and soft tissue infections (SSTIs), and MRSA membrane vesicles (MVs) play a pivotal role in bacterial pathogenesis and the modulation of the host immune response. We aimed to investigate the interaction between MRSA MVs and epithelial cells. In this study, MVs were isolated from an MRSA culture supernatant using the ELD method, comprising an electrophoretic technique used in combination with a 300 kDa cut-off dialysis bag. The proteomic analysis of the MRSA MVs via mass spectrometry showed that shared and distinct proteins exist in the MVs from clinical MRSA isolates with different genetic backgrounds, such as health-care-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA). These MRSA MVs were found to suppress the proliferation and increase the apoptosis of HaCaT cells. We conducted qPCR array, quantitative real-time PCR (qRT-PCR), and Western blotting (WB) analyses, and the results indicated that BCL2 antagonist/killer 1 (Bak1) may be involved in the apoptosis of HaCaT epithelial cells. Our findings suggest that MRSA MVs inhibit the proliferation and induce the apoptosis of epithelial cells.
Granulicatella spp., a Causative Agent of Infective Endocarditis in Children
Authors: Albano Chiara , Bagarello Sara , Giordano Salvatore , Sanfilippo Maria Fiorella , Comparato Calogero , Scardino Giuseppe , Garbo Valeria , Boncori Giovanni , Condemi Anna , Cascio Antonio , Colomba Claudia
Published: November 2022

Granulicatella spp. are non-motile, non-sporulating, facultatively anaerobic Gram-positive cocci. Throughout the literature, these organisms have been referred to by several names, such as “nutritionally deficient streptococci”, “vitamin-B dependent streptococci” and “pyridoxal-dependent streptococci”, because of their fastidious nutritional requirements, which can often make culture isolation challenging. Known to be a member of the normal microbiota of the human oral cavity and urogenital and intestinal tracts, similar to other streptococci, Granulicatella spp. can cause bacteremia, sepsis and infective endocarditis. Considering the difficulty in growing this organism on culture medium, the fact that it is now included among the bacteria known to be responsible for culture-negative infective endocarditis suggests that its pathogenic role could be highly underestimated. Moreover, being considered such a rare causative agent, it is not a target of standard antibiotic empiric treatment. We present a rare case of G. elegans endocarditis in a young child and review the medical literature on Granulicatella endocarditis in the pediatric population, with the aim of sharing knowledge about this microorganism, which can be challenging for a clinician who is not familiar with it.
Interactions of Antibacterial Naphthoquinones with Mesoporous Silica Surfaces: A Physicochemical and Theoretical Approach
Authors: Corpus-Mendoza César Iván , de Loera Denisse , López-López Lluvia Itzel , Acosta Brenda , Vega-Rodríguez Sarai , Navarro-Tovar Gabriela
Published: November 2022

1,4−naftoquinone (NQ) molecules have been extensively evaluated as potent antibacterial compounds; however, their use is limited, since they have low water solubility and exhibit toxicities in healthy eukaryotic cells. A possible path to overcoming these challenges is the use of particulate vehicles, such as SBA-15, which is a biocompatible and biodegradable mesoporous silica material, that may enhance drug delivery and decrease dosages. In this work, an isotherm model-based adsorption of three NQs into SBA-15 microparticles was evaluated. Interactions between NQs and SBA-15 microparticles were modeled at the B3LYP/6-31+G(d,p) level of theory to understand the nature of such interactions. The results demonstrated that the adsorption of NQ, 2NQ, and 5NQ into SBA-15 fit the Freundlich adsorption model. According to theorical studies, physisorption is mediated by hydrogen bonds, while the most stable interactions occur between the carbonyl group of NQ and silica surfaces. Both experimental and theoretical results contribute to a deeper understanding of the use of SBA-15 or similar particles as nanovehicles in such a way that NQs can be modified in carbonyl or C3 to enhance adsorptions. The theoretical and experimental results were in accordance and contribute to a deeper understanding of how interactions between NQ-type molecules and SiO2 materials occur.