bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumption of a Low Carbohydrate Diet in Overweight or Obese Pregnant Women Is Associated with Longer Gestation of Pregnancy
Authors: Tanner Helen , Barrett Helen L. , Callaway Leonie K. , Wilkinson Shelley A. , Dekker Nitert Marloes
Published: October 2021

Studies of obstetric outcomes in women consuming low-carbohydrate diets have reported conflicting results. Most studies have defined low-carbohydrate diets by the percentage that carbohydrates contribute to overall energy intake, rather than by an absolute amount in grams per day (g/d). We hypothesised that a low absolute carbohydrate diet affects obstetric outcomes differently than a low percentage carbohydrate diet. Dietary data were collected from overweight or obese women in the Study of Probiotic IN Gestational diabetes at 16- and 28-weeks’ gestation. Obstetric outcomes were compared between women whose carbohydrate intake was in the lowest quintile vs quintiles 2–5. Mean gestation was increased in women whose absolute carbohydrate intake was in the lowest quintile at 16 and at both 16- and 28-weeks’ gestation compared with all other women (16: 39.7 vs. 39.1 weeks, p = 0.008; 16 and 28: 39.8 vs. 39.1, p = 0.005). In linear regression analysis, a low absolute carbohydrate intake at 16 and at 28 weeks’ gestation was associated with increased gestation at delivery (16: p = 0.04, adjusted R2 = 0.15, 28: p = 0.04, adjusted R2 = 0.17). The coefficient of beta at 16 weeks’ gestation was 0.50 (95% CI 0.03–0.98) and at 28 weeks’ gestation was 0.51 (95%CI 0.03–0.99) meaning that consumption of a low absolute carbohydrate diet accounted for an extra 3.5 days in gestational age. This finding was not seen in women whose percentage carbohydrate intake was in the lowest quintile. Low-carbohydrate consumption in pregnancy is associated with increased gestational age at delivery.
Factors Related to Diet Quality: A Cross-Sectional Study of 1055 University Students
Authors: Ramón-Arbués Enrique , Granada-López José-Manuel , Martínez-Abadía Blanca , Echániz-Serrano Emmanuel , Antón-Solanas Isabel , Jerue Benjamin Adam
Published: October 2021

Given that there is only a limited body of evidence available concerning the dietary habits of Spanish university students, the present study assesses the quality of this group’s diet, their adherence to the National Food-Based Dietary Guidelines, and the predictive factors of their diet quality. To do so, a cross-sectional study was performed on a sample of 1055 students. The quality of the participants’ diets was then analysed by using the Spanish Healthy Eating Index, and then their level of compliance was assessed in light of the dietary recommendations put forth by the Spanish Society for Community Nutrition. According to these standards, only 17.4% of the participants had a healthy diet. The level of compliance with the recommendations was poor, highlighting especially the low levels of “fruit” and “vegetables” that they consumed as well as high levels of “cold meats and cuts” and “sweets”. The factors that predicted a worse diet are being male, living alone, low levels of physical activity, smoking, high alcohol intake, leading a sedentary lifestyle, psychological distress, and insomnia (p < 0.005). Furthermore, participants with low or high body weights showed signs of a higher quality diet (p < 0.001). The present findings suggest that a significant proportion of university students ought to change their dietary habits; these also attest to the importance of developing strategies that are directly targeted at university students in order to promote a healthy diet.
The Impact of Multispecies Probiotics on Calcium and Magnesium Status in Healthy Male Rats
Authors: Suliburska Joanna , Harahap Iskandar Azmy , Skrypnik Katarzyna , Bogdański Paweł
Published: October 2021

Although probiotics have been discovered in numerous diseases in the last decade, there is little consensus on the relationship between probiotic properties and minerals balance and their distribution in the organism. This research aimed to evaluate the calcium (Ca) and magnesium (Mg) status in rats on a diet containing multispecies probiotics. Thirty male 10-week-old Wistar rats were selected and divided into three groups (n = 10 rats)—a group fed a standard diet (C), a group fed a low-dose of multispecies probiotics with 2.5 × 109 CFU per day (LD), and a group fed high-dose of multispecies probiotics 1 × 1010 CFU per day (HD) for 6 weeks. The results revealed that HD intake significantly increased the Ca concentration in hair and Mg concentration in femur bones. A significant positive correlation was found between calcium and magnesium levels in hair. The Ca/Mg molar ratio was lower in testicles in the groups with probiotics. In conclusion, multispecies probiotics altered the Ca concentration in hair and Mg level in femur bone, and also changed the molar ratio of these elements in testicles in male rats.
Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children
Authors: Hayman Thomas , Hickey Peter , Amann-Zalcenstein Daniela , Bennett Cavan , Ataide Ricardo , Sthity Rahvia Alam , Khandaker Afsana Mim , Islam Kazi Munisul , Stracke Katharina , Yassi Nawaf , Watson Rosie , Long Julie , Westcott Jamie , Krebs Nancy F. , King Janet C. , Black Robert E. , Islam Md. Munirul , McDonald Christine M. , Pasricha Sant-Rayn
Published: October 2021

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.
Retrospective Evaluation on the Use of a New Polysaccharide Complex in Managing Paediatric Type 1 Diabetes with Metabolic Syndrome (MetS)
Authors: Stagi Stefano , Papacciuoli Valeria , Ciofi Daniele , Piccini Barbara , Farello Giovanni , Toni Sonia , Ferrari Marta , Chiarelli Francesco
Published: October 2021

Background: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. Aims: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). Patients and Methods: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years’ standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5–15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4–15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. Results: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). Conclusions: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.
Metabolic Syndrome and Sarcopenia
Authors: Nishikawa Hiroki , Asai Akira , Fukunishi Shinya , Nishiguchi Shuhei , Higuchi Kazuhide
Published: October 2021

Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.
Clinical Implications of Malnutrition in the Management of Patients with Pancreatic Cancer: Introducing the Concept of the Nutritional Oncology Board
Authors: Rovesti Giulia , Valoriani Filippo , Rimini Margherita , Bardasi Camilla , Ballarin Roberto , Di Benedetto Fabrizio , Menozzi Renata , Dominici Massimo , Spallanzani Andrea
Published: October 2021

Pancreatic cancer represents a very challenging disease, with an increasing incidence and an extremely poor prognosis. Peculiar features of this tumor entity are represented by pancreatic exocrine insufficiency and an early and intense nutritional imbalance, leading to the highly prevalent and multifactorial syndrome known as cancer cachexia. Recently, also the concept of sarcopenic obesity has emerged, making the concept of pancreatic cancer malnutrition even more multifaceted and complex. Overall, these nutritional derangements play a pivotal role in contributing to the dismal course of this malignancy. However, their relevance is often underrated and their assessment is rarely applied in clinical daily practice with relevant negative impact for patients’ outcome in neoadjuvant, surgical, and metastatic settings. The proper detection and management of pancreatic cancer-related malnutrition syndromes are of primary importance and deserve a specific and multidisciplinary (clinical nutrition, oncology, etc.) approach to improve survival, but also the quality of life. In this context, the introduction of a “Nutritional Oncology Board” in routine daily practice, aimed at assessing an early systematic screening of patients and at implementing nutritional support from the time of disease diagnosis onward seems to be the right path to take.
The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency
Authors: Staretz-Chacham Orna , Pode-Shakked Ben , Kristal Eyal , Abraham Smadar Yaala , Porper Keren , Wormser Ohad , Shelef Ilan , Anikster Yair
Published: October 2021

Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). Objective: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. Results: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients’ quality of life (QOL) was not significantly improved. Conclusions: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.
Non-Bovine Species and the Risk to Effective Control of Bovine Viral Diarrhoea (BVD) in Cattle
Authors: Evans Caitlin A. , Reichel Michael P.
Published: October 2021

Bovine viral diarrhoea virus (BVDV) is an economically important and highly prevalent virus of domestic cattle. Infections with BVDV may lead to both, reproductive and immunological effects that can result in widespread calf losses and increased susceptibility to diseases, such as mastitis and respiratory disease. While BVDV is generally considered to be host specific, it and other Pestivirus species, such as Border disease virus (BDV) in sheep, have been shown to be infecting species other than those from which they were originally isolated from. Recently BVDV was placed on the OIE’s list of notifiable disease and control and eradication programmes for BVDV have been developed throughout much of Europe, the United States, and the United Kingdom. While some countries, including Sweden and Ireland have successfully implemented eradication programmes, other countries such as New Zealand and Australia are still in the early stages of BVDV control. Despite effective control methods, incursions of BVDV into previously cleared herds still occur. While the cause of these incursions is often due to lapses in control methods, the ability of ruminant pestiviruses to infect species other than cattle poses the question as to whether non-bovine species could be impeding the success of BVDV eradication and control. As such, the aim of this review is to make mention of what is known about the cross-species transmission of BVDV, BDV and other pestiviruses between cattle and non-bovine ungulate species and draw conclusions as to the risk non-bovine species pose to the successful control and eradication of BVDV from cattle.
Surveillance along the Rio Grande during the 2020 Vesicular Stomatitis Outbreak Reveals Spatio-Temporal Dynamics of and Viral RNA Detection in Black Flies
Authors: Young Katherine I. , Valdez Federico , Vaquera Christina , Campos Carlos , Zhou Lawrence , Vessels Helen K. , Moulton J. Kevin , Drolet Barbara S. , Rozo-Lopez Paula , Pelzel-McCluskey Angela M. , Peters Debra C. , Rodriguez Luis L. , Hanley Kathryn A.
Published: October 2021

Vesicular stomatitis virus (VSV) emerges periodically from its focus of endemic transmission in southern Mexico to cause epizootics in livestock in the US. The ecology of VSV involves a diverse, but largely undefined, repertoire of potential reservoir hosts and invertebrate vectors. As part of a larger program to decipher VSV transmission, we conducted a study of the spatiotemporal dynamics of Simulium black flies, a known vector of VSV, along the Rio Grande in southern New Mexico, USA from March to December 2020. Serendipitously, the index case of VSV-Indiana (VSIV) in the USA in 2020 occurred at a central point of our study. Black flies appeared soon after the release of the Rio Grande’s water from an upstream dam in March 2020. Two-month and one-year lagged precipitation, maximum temperature, and vegetation greenness, measured as Normalized Difference Vegetation Index (NDVI), were associated with increased black fly abundance. We detected VSIV RNA in 11 pools comprising five black fly species using rRT-PCR; five pools yielded a VSIV sequence. To our knowledge, this is the first detection of VSV in the western US from vectors that were not collected on premises with infected domestic animals.
Differentiation of Aspergillus flavus from Aspergillus oryzae Targeting the cyp51A Gene
Authors: Nargesi Sanaz , Abastabar Mahdi , Valadan Reza , Mayahi Sabah , Youn Jung-Ho , Hedayati Mohammad Taghi , Seyedmousavi Seyedmojtaba
Published: October 2021

Aspergillus flavus is one of the most important agents of invasive and non-invasive aspergillosis, especially in tropical and subtropical regions of the world, including Iran. Aspergillus oryzae is closely related to A. flavus, and it is known for its economic importance in traditional fermentation industries. Reports of infection due to A. oryzae are scarce. Several studies reported that differentiating these two species in clinical laboratories is not possible using MALDI-TOF or by targeting fungal barcode genes, such as Internal Transcribed Spacer (ITS) and β-tubulin (benA). The species-level identification of causative agents and the determination of antifungal susceptibility patterns can play significant roles in the outcome of aspergillosis. Here, we aimed to investigate the discriminatory potential of cyp51A PCR-sequencing versus that of the ITS, benA and calmodulin (CaM) genes for the differentiation of A. flavus from A. oryzae. In a prospective study investigating the molecular epidemiology of A. flavus in Iran between 2008 and 2018, out of 200 clinical isolates of A. flavus, 10 isolates showed >99% similarity to both A. flavus and A. oryzae. Overall, the ITS, β-tubulin and CaM genes did not fulfil the criteria for differentiating these 10 isolates. However, the cyp51A gene showed promising results, which warrants further studies using a larger set of isolates from more diverse epidemiological regions of the world.
Knowledge, Attitudes and Practices on Rabies among Human and Animal Health Professionals in Senegal
Authors: Ba Mouhamadou Faly , Kane Ndèye Mbacké , Diallo Mamadou Kindi Korka , Bassoum Oumar , Boh Oumy Kaltome , Mboup Fatoumata Zahra Mohamed , Faye El Hadji Bilal , Bedekelabou Andre Pouwedeou , Dieng Sara Danièle , Diop Fatimata Niang , Badiane Médoune , Ridde Valéry , Faye Adama
Published: October 2021

Rabies is still a public health problem in Senegal. This study aimed to assess the knowledge, attitudes and practices on rabies among human and animal health professionals. It was a cross-sectional, descriptive and analytical study conducted in the Kaffrine district. Data were collected from 28 June to 01 July 2021. An exhaustive recruitment was done, and the final sample size was 95 health professionals. R software was used for descriptive, bivariate and multivariate analyses. Health professionals with sufficient knowledge, positive attitudes and good practices in relation to rabies represented 35.8%, 26.3% and 45.3% of the study respectively. The results of the multivariate analysis showed that professionals who worked in urban areas (AOR = 11.10; 95% CI = [3.50–41.69]) and who worked in animal health (AOR = 7.45; 95% CI = [1.16–70.40]) were more likely to have sufficient knowledge about rabies. Professionals with tertiary education (AOR = 12.40; CI95% = [1.80–268.00]) and with sufficient knowledge (AOR = 3.41; CI95% = [1.01–12.70]) were more likely to have a positive attitude about rabies. Professionals with a positive attitude about rabies (AOR = 3.23; 95% CI = [1.08–10.70]) were more likely to have a good practice when presented with an animal bite case. These results suggest that improving health professionals’ knowledge about rabies is essential in order to influence their attitudes and practices against rabies.
One Health Perspectives on New Emerging Viral Diseases in African Wild Great Apes
Authors: Azevedo Denis S. , Duarte José Lucas C. , Freitas Carlos Felipe G. , Soares Karoline L. , Sousa Mônica S. , Sousa Eduardo Sérgio S. , Lucena Ricardo B.
Published: October 2021

The most recent emerging infectious diseases originated in animals, mainly in wildlife reservoirs. Mutations and recombination events mediate pathogen jumps between host species. The close phylogenetic relationship between humans and non-human primates allows the transmission of pathogens between these species. These pathogens cause severe impacts on public health and impair the conservation of habituated or non-habituated wild-living apes. Constant exposure of great apes to human actions such as hunting, deforestation, the opening of roads, and tourism, for example, contributes to increased interaction between humans and great apes. In spite of several studies emphasizing the risks of pathogen transmission between animals and humans, outbreaks of the reverse transmission of infectious agents threatening wildlife still occur on the African continent. In this context, measures to prevent the emergence of new diseases and conservation of primate species must be based on the One Health concept; that is, they must also ensure the monitoring of the environment and involve political and social aspects. In this article, we review and discuss the anthropological aspects of the transmission of diseases between people and wild primates and discuss new anthropozoonotic diseases in great apes in Africa from studies published between 2016 and 2020. We conclude that the health of great apes also depends on monitoring the health of human populations that interact with these individuals.
STAT1-Dependent Recruitment of Ly6ChiCCR2+ Inflammatory Monocytes and M2 Macrophages in a Helminth Infection
Authors: Becerra-Díaz Mireya , Ledesma-Soto Yadira , Olguín Jonadab E. , Sánchez-Barrera Angel , Mendoza-Rodríguez Mónica G. , Reyes Sandy , Satoskar Abhay R. , Terrazas Luis I.
Published: October 2021

Signal Transducer and Activator of Transcription (STAT) 1 signaling is critical for IFN-γ-mediated immune responses and resistance to protozoan and viral infections. However, its role in immunoregulation during helminth parasitic infections is not fully understood. Here, we used STAT1−/− mice to investigate the role of this transcription factor during a helminth infection caused by the cestode Taenia crassiceps and show that STAT1 is a central molecule favoring susceptibility to this infection. STAT1−/− mice displayed lower parasite burdens at 8 weeks post-infection compared to STAT1+/+ mice. STAT1 mediated the recruitment of inflammatory monocytes and the development of alternatively activated macrophages (M2) at the site of infection. The absence of STAT1 prevented the recruitment of CD11b+Ly6ChiLy6G− monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b+Ly6ChiLy6G− cells. Importantly, CD11b+Ly6ChiLy6G− cells highly expressed PDL-1 and suppressed T-cell proliferation elicited by anti-CD3 stimulation. PDL-1+ cells were mostly absent in STAT1−/− mice. Furthermore, only STAT1+/+ mice developed M2 macrophages at 8 weeks post-infection, although macrophages from both T. crassiceps-infected STAT1+/+ and STAT1−/− mice responded to IL-4 in vitro, and both groups of mice were able to produce the Th2 cytokine IL-13. This suggests that CD11b+CCR2+Ly6ChiLy6G− cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b+CCR2+Ly6ChiLy6G− cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.
Discovery of a Novel Class of Norovirus Inhibitors with High Barrier of Resistance
Authors: Van Dycke Jana , Puxeddu Michela , La Regina Giuseppe , Mastrangelo Eloise , Tarantino Delia , Rymenants Jasper , Sebastiani Jessica , Nalli Marianna , Matthijnssens Jelle , Neyts Johan , Silvestri Romano , Rocha-Pereira Joana
Published: October 2021

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting in ~219,000 deaths annually and a societal cost of ~USD60 billion. There are no antivirals or vaccines available to treat and/or prevent HuNoV. In this study, we performed a large-scale phenotypical antiviral screening using the mouse norovirus (MNV), which included ~1000 drug-like small molecules from the Drug Design and Synthesis Centre (Sapienza University, Rome). Compound 3-((3,5-dimethylphenyl)sulfonyl)-5-chloroindole-N-(phenylmethanol-4-yl)-2.carboxamide (compound 1) was identified as an inhibitor of MNV replication with an EC50 of 0.5 ± 0.1 µM. A series of 10 analogs were synthesized of which compound 6 showed an improved potency/selectivity (EC50 0.2 ± 0.1 µM) against MNV; good activity was also observed against the HuNoV GI replicon (EC50 1.2 ± 0.6 µM). Time-of-drug-addition studies revealed that analog 6 acts at a time point that coincides with the onset of viral RNA replication. After six months of selective pressure, two compound 6res variants were independently selected, both harboring one mutation in VPg and three mutations in the RdRp. After reverse engineering S131T and Y154F as single mutations into the MNV backbone, we did not find a markedly compound 6res phenotype. In this study, we present a class of novel norovirus inhibitors with a high barrier to resistance and in vitro antiviral activity.
Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics
Authors: Panossian Alexander , Abdelfatah Sara , Efferth Thomas
Published: October 2021

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up- or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.
Naphthyridine Derivatives Induce Programmed Cell Death in Naegleria fowleri
Authors: Rizo-Liendo Aitor , Arberas-Jiménez Iñigo , Martin-Encinas Endika , Sifaoui Ines , Reyes-Batlle María , Chao-Pellicer Javier , Alonso Concepción , Palacios Francisco , Piñero José E. , Lorenzo-Morales Jacob
Published: October 2021

Primary amoebic encephalitis (PAM) caused by the opportunistic pathogen Naegleria fowleri is characterized as a rapid and lethal infection of the brain which ends in the death of the patient in more than 90% of the reported cases. This amoeba thrives in warm water bodies and causes infection after individuals perform risky activities such as splashing or diving, mostly in non-treated water bodies such as lakes and ponds. Moreover, the infection progresses very fast and no fully effective molecules have currently been found to treat PAM. In this study, naphthyridines fused with chromenes or chromenones previously synthetized by the group were tested in vitro against the trophozoite stage of two strains of N. fowleri. In addition, the most active molecule was evaluated in order to check the induction of programmed cell death (PCD) in the treated amoebae. Compound 3 showed good anti-Naegleria activity (61.45 ± 5.27 and 76.61 ± 10.84 µM, respectively) against the two different strains (ATCC® 30808 and ATCC® 30215) and a good selectivity compared to the cytotoxicity values (>300 µM). In addition, it was able to induce PCD, causing DNA condensation, damage at the cellular membrane, reduction in mitochondrial membrane potential and ATP levels, and ROS generation. Hence, naphthyridines fused with chromenes or chromenones could be potential therapeutic agents against PAM in the near future.
Pharmacometabolomics by NMR in Oncology: A Systematic Review
Authors: Gómez-Cebrián Nuria , Vázquez Ferreiro Pedro , Carrera Hueso Francisco Javier , Poveda Andrés José Luis , Puchades-Carrasco Leonor , Pineda-Lucena Antonio
Published: October 2021

Pharmacometabolomics (PMx) studies aim to predict individual differences in treatment response and in the development of adverse effects associated with specific drug treatments. Overall, these studies inform us about how individuals will respond to a drug treatment based on their metabolic profiles obtained before, during, or after the therapeutic intervention. In the era of precision medicine, metabolic profiles hold great potential to guide patient selection and stratification in clinical trials, with a focus on improving drug efficacy and safety. Metabolomics is closely related to the phenotype as alterations in metabolism reflect changes in the preceding cascade of genomics, transcriptomics, and proteomics changes, thus providing a significant advance over other omics approaches. Nuclear Magnetic Resonance (NMR) is one of the most widely used analytical platforms in metabolomics studies. In fact, since the introduction of PMx studies in 2006, the number of NMR-based PMx studies has been continuously growing and has provided novel insights into the specific metabolic changes associated with different mechanisms of action and/or toxic effects. This review presents an up-to-date summary of NMR-based PMx studies performed over the last 10 years. Our main objective is to discuss the experimental approaches used for the characterization of the metabolic changes associated with specific therapeutic interventions, the most relevant results obtained so far, and some of the remaining challenges in this area.
Design and Synthesis of Newly Synthesized Acrylamide Derivatives as Potential Chemotherapeutic Agents against MCF-7 Breast Cancer Cell Line Lodged on PEGylated Bilosomal Nano-Vesicles for Improving Cytotoxic Activity
Authors: Zaki Islam , Abou-Elkhair Reham A. I. , Abu Almaaty Ali H. , A. Abu Ali Ola , Fayad Eman , Ahmed Gaafar Ahmed Gaafar , Zakaria Mohamed Y.
Published: October 2021

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4-(furan-2-ylmethylene)-2-(3,4,5-trimethoxyphenyl)oxazol-5(4H)–one (1), and they are evaluated for their inhibitory activity against β-tubulin polymerization. The target molecules 2–5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent β-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. 23 full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE–mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = −22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound’s cytotoxic activity (IC50 = 0.75 ± 0.03 µM) instead of (IC50 = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.
Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.
Authors: Czechowicz Paulina , Neubauer Damian , Nowicka Joanna , Kamysz Wojciech , Gościniak Grażyna
Published: October 2021

Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.
Chitosan-Coated PLGA Nanoparticles Encapsulating Triamcinolone Acetonide as a Potential Candidate for Sustained Ocular Drug Delivery
Authors: Dandamudi Madhuri , McLoughlin Peter , Behl Gautam , Rani Sweta , Coffey Lee , Chauhan Anuj , Kent David , Fitzhenry Laurence
Published: October 2021

The current treatment for the acquired retinal vasculopathies involves lifelong repeated intravitreal injections of either anti-vascular endothelial growth factor (VEGF) therapy or modulation of inflammation with steroids. Consequently, any treatment modification that decreases this treatment burden for patients and doctors alike would be a welcome intervention. To that end, this research aims to develop a topically applied nanoparticulate system encapsulating a corticosteroid for extended drug release. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) supports the controlled release of the encapsulated drug, while surface modification of these NPs with chitosan might prolong the mucoadhesion ability leading to improved bioavailability of the drug. Triamcinolone acetonide (TA)-loaded chitosan-coated PLGA NPs were fabricated using the oil-in-water emulsion technique. The optimized surface-modified NPs obtained using Box-Behnken response surface statistical design were reproducible with a particle diameter of 334 ± 67.95 to 386 ± 15.14 nm and PDI between 0.09 and 0.15. These NPs encapsulated 55–57% of TA and displayed a controlled release of the drug reaching a plateau in 27 h. Fourier-transform infrared spectroscopic (FTIR) analysis demonstrated characteristic peaks for chitosan (C-H, CONH2 and C-O at 2935, 1631 and 1087 cm−1, respectively) in chitosan-coated PLGA NPs. This result data, coupled with positive zeta potential values (ranged between +26 and +33 mV), suggests the successful coating of chitosan onto PLGA NPs. Upon coating of the NPs, the thermal stability of the drug, polymer, surfactant and PLGA NPs have been enhanced. The characteristics of the surface-modified NPs supports their use as potential candidates for topical ocular drug delivery for acquired retinal vasculopathies.
Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications
Authors: Vrettos Napoleon-Nikolaos , Roberts Clive J. , Zhu Zheying
Published: October 2021

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.
Engineered Exosomes-Based Photothermal Therapy with MRI/CT Imaging Guidance Enhances Anticancer Efficacy through Deep Tumor Nucleus Penetration
Authors: Yang Min , Wang Xiaohui , Pu Fang , Liu Ying , Guo Jia , Chang Shuzhuo , Sun Guoying , Peng Yinghua
Published: October 2021

Exosomes, as natural nanovesicles, have become a spotlight in the field of cancer therapy due to their reduced immunogenicity and ability to overcome physiological barriers. However, the tumor targeting ability of exosomes needs to be improved before its actual application. Herein, a multiple targeted engineered exosomes nanoplatform was constructed through rare earth element Gd and Dy-doped and TAT peptide-modified carbon dots (CDs:Gd,Dy-TAT) encapsulated into RGD peptide engineered exosomes (Exo-RGD), which were used to enhance the effect of cancer imaging diagnosis and photothermal therapy. In vitro and in vivo experiments showed that the resulting CDs:Gd,Dy-TAT@Exo-RGD could effectively accumulate at cancer site with an increased concentration owing to the targeting peptides modification and exosomes encapsulation. The tumor therapy effects of mice treated with CDs:Gd,Dy-TAT@Exo-RGD were heightened compared with mice from the CDs:Gd,Dy control group. After intravenous injection of CDs:Gd,Dy-TAT@Exo-RGD into tumor-bearing mice, the temperature of tumors rose to above 50 °C under NIR irradiation and the localized hyperpyrexia induced by CDs could remarkably ablate tumors. The survival rate of the mice was 100% after 60 days. In addition, the CDs:Gd,Dy-TAT@Exo-RGD exhibited higher MRI/CT imaging contrast enhancement of tumor sites than that of CDs:Gd,Dy. Our study identified that engineered exosomes are a powerful tool for encapsulating multiple agents to enhance cancer theranostic efficiency and provide insight into precise personalized nanomedicine.
Proving Nanoscale Chiral Interactions of Cyclodextrins and Propranolol Enantiomers by Means of SERS Measurements Performed on a Solid Plasmonic Substrate
Authors: Știufiuc Gabriela Fabiola , Toma Valentin , Onaciu Anca , Chiș Vasile , Lucaciu Constantin Mihai , Știufiuc Rareș Ionuț
Published: October 2021

Chiral separation is an important issue for the pharmaceutical industry. Over the years, several separation methods have been developed, mainly based on chromatography. Their working principle is based on the formation of transient diastereoisomers, but the very subtle nanoscale interactions responsible for separation are not always understood. Recently, Raman and surface-enhanced Raman (SERS) spectroscopy have provided promising results in this field. Here we present Raman/SERS experimental data that provide useful information concerning the nanoscale interactions between propranolol enantiomers and α, β, and γ cyclodextrins. Raman spectroscopy was used to prove the formation of host–guest intermolecular complexes having different geometries of interaction. The occurrence of new vibrational bands and a change in the intensities of others are direct proofs of complexes’ formation. These observations were confirmed by DFT calculations. By performing SERS measurements on a new type of plasmonic substrate, we were able to prove the intermolecular interactions responsible for PRNL discrimination. It turned out that the interaction strength between the substrate and the intermolecular complexes is of paramount importance for SERS-based chiral discrimination. This approach could represent a very good starting point for the evaluation of molecular interactions manifesting between other pharmaceutical compounds and different classes of chiral selectors.
The Effects of a Short Self-Assembling Peptide on the Physical and Biological Properties of Biopolymer Hydrogels
Authors: Chowdhuri Sumit , Ghosh Moumita , Adler-Abramovich Lihi , Das Debapratim
Published: October 2021

Hydrogel scaffolds have attracted much interest in the last few years for applications in the field of bone and cartilage tissue engineering. These scaffolds serve as a convenient three-dimensional structure on which cells can grow while sensing the native environment. Natural polymer-based hydrogels are an interesting choice for such purposes, but they lack the required mechanical properties. In contrast, composite hydrogels formed by biopolymers and short peptide hydrogelators possess mechanical characteristics suitable for osteogenesis. Here, we describe how combining the short peptide hydrogelator, Pyrene-Lysine-Cysteine (PyKC), with other biopolymers, can produce materials that are suitable for tissue engineering purposes. The presence of PyKC considerably enhances the strength and water content of the composite hydrogels, and confers thixotropic behavior. The hyaluronic acid-PyKC composite hydrogels were shown to be biocompatible, with the ability to support osteogenesis, since MC3 T3-E1 osteoblast progenitor cells grown on the materials displayed matrix calcification and osteogenic differentiation. The osteogenesis results and the injectability of these composite hydrogels hold promise for their future utilization in tissue engineering.
Kinase Inhibition in Relapsed/Refractory Leukemia and Lymphoma Settings: Recent Prospects into Clinical Investigations
Authors: Machado Caio Bezerra , de Pinho Pessoa Flávia Melo Cunha , da Silva Emerson Lucena , da Costa Pantoja Laudreísa , Ribeiro Rodrigo Monteiro , de Moraes Filho Manoel Odorico , de Moraes Maria Elisabete Amaral , Montenegro Raquel Carvalho , Burbano Rommel Mário Rodriguez , Khayat André Salim , Moreira-Nunes Caroline Aquino
Published: October 2021

Cancer is still a major barrier to life expectancy increase worldwide, and hematologic neoplasms represent a relevant percentage of cancer incidence rates. Tumor dependence of continuous proliferative signals mediated through protein kinases overexpression instigated increased strategies of kinase inhibition in the oncologic practice over the last couple decades, and in this review, we focused our discussion on relevant clinical trials of the past five years that investigated kinase inhibitor (KI) usage in patients afflicted with relapsed/refractory (R/R) hematologic malignancies as well as in the pharmacological characteristics of available KIs and the dissertation about traditional chemotherapy treatment approaches and its hindrances. A trend towards investigations on KI usage for the treatment of chronic lymphoid leukemia and acute myeloid leukemia in R/R settings was observed, and it likely reflects the existence of already established treatment protocols for chronic myeloid leukemia and acute lymphoid leukemia patient cohorts. Overall, regimens of KI treatment are clinically manageable, and results are especially effective when allied with tumor genetic profiles, giving rise to encouraging future prospects of an era where chemotherapy-free treatment regimens are a reality for many oncologic patients.
PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells
Authors: Esfahani Maedeh Koohi Moftakhari , Alavi Seyed Ebrahim , Cabot Peter J. , Islam Nazrul , Izake Emad L.
Published: October 2021

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.