bluuebunny/crossref_metadata_2025 huggingface dataset:
Food Insecurity and Maternal Diet Influence Human Milk Composition between the Infant’s Birth and 6 Months after Birth in Central-Africa
Authors: Bottin Jeanne H. , Eussen Simone R. B. M. , Igbinijesu Aisosa J. , Mank Marko , Koyembi Jean-Christophe Junior , Nyasenu Yawo Tufa , Ngaya Gilles , Mad-Bondo Daniel , Kongoma Jean-Bertrand , Stahl Bernd , Sansonetti Philippe J. , Bourdet-Sicard Raphaëlle , Moya-Alvarez Violeta
Published: September 2022

Although the World Health Organization (WHO) and UNICEF recommend that infants should be exclusively breastfed for the first 6 months of life, evidence is scarce on how the mother’s undernourishment status at delivery and maternal dietary factors influence human milk (HM) composition during the first 6 months of life in regions with high food insecurity. The maternal undernourishment status at delivery, maternal diet, and HM nutrients were assessed among 46 women and their 48 vaginally born infants in Bangui at 1, 4, 11, 18, and 25 weeks after birth through 24-h recalls and food consumption questionnaires from December 2017 to June 2019 in the context of the "Mother-to-Infant TransmIssion of microbiota in Central-Africa" (MITICA) study. High food insecurity indexes during the follow-up were significantly associated with them having lower levels of many of the human milk oligosaccharides (HMOs) that were measured and with lower levels of retinol (aß-coef = −0.2, p value = 0.04), fatty acids (aß-coef = −7.2, p value = 0.03), and amino acids (aß-coef = −2121.0, p value < 0.001). On the contrary, women from food-insecure households displayed significantly higher levels of lactose in their HM (aß-coef = 3.3, p value = 0.02). In parallel, the consumption of meat, poultry, and fish was associated with higher HM levels of many of the HMOs that were measured, total amino acids (aß-coef = 5484.4, p value < 0.001), and with lower HM levels of lactose (aß-coef = −15.6, p value = 0.01). Food insecurity and maternal diet had a meaningful effect on HM composition with a possible impact being an infant undernourishment risk. Our results plead for consistent actions on food security as an effective manner to influence the nutritional content of HM and thereby, potentially improve infant survival and healthy growth.
Translation and Validation of the Greek Version of the Evidence-Based Practice Competency Questionnaire for Registered Nurses (EBP-COQ Prof©)
Authors: Schetaki Stefania , Patelarou Evridiki , Giakoumidakis Konstantinos , Trivli Alexandra , Kleisiaris Christos , Patelarou Athina
Published: September 2022

(1) Background: Evidence-based nursing is the benchmark of the nursing profession. It is widely recognized that evidence enhances knowledge, skills, and competencies in nursing education and thus the quality of patient care. Although several proposals have been introduced to reinforce nurses through education in evidence-based practice (EBP) for clinical practice, there is no validated EBP competence tool to determine how nurses approach evidence-based nursing in healthcare practices in Greece. Therefore, the aim of the present study was to translate and validate the Greek version of the Evidence-Based Practice Competency Questionnaire, Professional version (EBP-COQ Prof©). (2) Methods: A cross-sectional study was conducted in a sample of registered nurses working in the public sector. (3) Results: 414 clinical nurses were recruited in total with a response rate of 75.3% and a mean age of 43 years old. Most of the nursing personnel were females, 354 (85.5%), and there were 60 (14.5%) males. Confirmatory factor analysis (CFA) showed a confirmation of the developer’s four-factor design. The estimated association between items on each scale showed a strong relationship. The competence questionnaire showed a high internal consistency between the components of attitude, knowledge, skills, and utilization. (4) Conclusions: The competence questionnaire shows a strong relationship between four the components, highlighting the four factors that should be promoted to improve the use of EBP nursing practices.
Serendipitous Discovery of a Competitive Inhibitor of FraB, a Salmonella Deglycase and Drug Target
Authors: Thirugnanasambantham Pankajavalli , Kovvali Sravya , Cool Austin , Gao Yuan , Sabag-Daigle Anice , Boulanger Erin F. , Mitton-Fry Mark , Capua Angela Di , Behrman Edward J. , Wysocki Vicki H. , Lindert Steffen , Ahmer Brian M. M. , Gopalan Venkat
Published: September 2022

Although salmonellosis, an infectious disease, is a significant global healthcare burden, there are no Salmonella-specific vaccines or therapeutics for humans. Motivated by our finding that FraB, a Salmonella deglycase responsible for fructose-asparagine catabolism, is a viable drug target, we initiated experimental and computational efforts to identify inhibitors of FraB. To this end, our recent high-throughput screening initiative yielded almost exclusively uncompetitive inhibitors of FraB. In parallel with this advance, we report here how a separate structural and computational biology investigation of FrlB, a FraB paralog, led to the serendipitous discovery that 2-deoxy-6-phosphogluconate is a competitive inhibitor of FraB (KI ~ 3 μM). However, this compound was ineffective in inhibiting the growth of Salmonella in a liquid culture. In addition to poor uptake, cellular metabolic transformations by a Salmonella dehydrogenase and different phosphatases likely undermined the efficacy of 2-deoxy-6-phosphogluconate in live-cell assays. These insights inform our ongoing efforts to synthesize non-hydrolyzable/-metabolizable analogs of 2-deoxy-6-phosphogluconate. We showcase our findings largely to (re)emphasize the role of serendipity and the importance of multi-pronged approaches in drug discovery.
Prevalence and Genotyping of HPV in Oral Squamous Cell Carcinoma in Northern Brazil
Authors: de Menezes Silvio , Miranda Yasmim , da Silva Yngrid , Carvalho Tábata , Alves Flávia , Silvestre Rodrigo , Oliveira-Filho Aldemir , de Alencar Menezes Tatiany , de Souza Fonseca Ricardo , Laurentino Rogério , Machado Luiz
Published: September 2022

Highly oncogenic human papillomavirus (HPV) is well known to be associated with and a risk factor for various types of oral carcinomas such as oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate and describe the HPV-induced OSCC prevalence and genotyping in the city of Belém, northern Brazil. This cross-sectional study features 101 participants who attended an oral pathology referral center in a dental college looking for diagnoses of oral lesions (OL). After signing the consent term and meeting the inclusion criteria, all participants went through a sociodemographic and epidemiological questionnaire. Then, OL were collected by excisional or incisional biopsy depending on OL size; after that, OL tissues were preserved in paraffin blocks to histopathological diagnoses. Afterwards, paraffin blocks were divided into benign and malignant/premalignant lesions based on the classification of potentially malignant disorders of the oral and oropharyngeal mucosa. Then, the paraffin blocks had DNA extraction performed by the ReliaPrep FFPE gDNA Miniprep method in order to identify HPV DNA of high oncogenic risk and low oncogenic risk. Then, the viral DNA was amplified and typed using the Inno-Lipa genotyping Extra II method, and the collected data were analyzed by Chi-square and G-tests. In total, 59/101 (58.4%) OL were malignant/premalignant lesions, of which OSCC was the most prevalent with 40/59 (67.7%) and 42/101 (41.6%) benign lesions. The most common area of OL incidence was upper gingiva 46/101 (45.5%). Regarding HPV DNA detection, approximately 27/101 (26.7%) had positive results; of these, 17/59 (28.8%) were malignant/premalignant lesions, and the most prevalent genotypes detected were 16, 18, 52 and 58, while among benign lesions, 10/42 (66.6%) had HPV-positive results, and the most prevalent genotypes detected were 6, 11 and 42. Age range was the only risk factor with a significant association between HPV and OSCC presence (p-value: 0.0004). A correlation between OSCC and oral HPV among analyzed samples could not be demonstrated in our small cohort.
Serological Survey of Aujeszky’s Disease in Wild Boar from Southeastern France
Authors: Laidoudi Younes , Davoust Bernard , Watier-Grillot Stéphanie , Oger Aurélie , Le Potier Marie-Frédérique , Deblanc Céline
Published: September 2022

Aujeszky’s disease virus (ADV), also known as pseudorabies virus, causes an important neurological infection with a major economic and health impact on animal husbandry. Here, we serologically screened muscle fluid from wild boar (Sus scrofa) for the presence of anti-ADV antibodies. Animals were caught during two hunting seasons (2019–2020 and 2021–2022) from three areas in southeastern France known to be endemic with wild boar populations. A total of 30.33% of the 399 tested animals scored positive for anti-glycoprotein B antibodies directed against ADV using a commercial competitive ELISA test. A significant effect (p-value < 0.0001) of the geographical location and animal age on ADV seroprevalence was observed. The results of this study confirmed the importance of wild boar in the epidemiology of ADV in southeastern France.
The New Haplotypes of Bartonella spp. and Borrelia burgdorferi Sensu Lato Identified in Lipoptena spp. (Diptera: Hippoboscidae) Collected in the Areas of North-Eastern Poland
Authors: Werszko Joanna , Świsłocka Magdalena , Witecka Joanna , Szewczyk Tomasz , Steiner-Bogdaszewska Żaneta , Wilamowski Konrad , Asman Marek
Published: September 2022

Deer keds are hematophagous ectoparasites (Diptera: Hippoboscidae) that mainly parasitize Cervidae. These flies are particularly important for animal health due to the occurrence of numerous pathogenic microorganisms. They may also attack humans and their bites may cause allergenic symptoms. The aim of the study was to identify the molecular characteristics of Borrelia burgdorferi sensu lato and Bartonella spp. pathogens detected in Lipoptena spp. sampled both from the hosts and from the environment. For identification of Bartonella spp and B. burgdorferi s. l., the primers specific to the rpoB and flaB gene fragments were used, respectively. The overall prevalence of B. burgdorferi s.l. DNA in Lipoptena cervi was 14.04%, including 14.8% infection in the tested group of winged specimens. The overall prevalence of Bartonella spp. was 57.02%. The presence of these bacteria was detected in 53.5% of specimens of L. cervi and 75.7% of L. fortisetosa. The phylogenetic analysis showed five new haplotypes of the rpoB gene of Bartonella sp. isolated from L. cervi/Lipoptena fortisetosa. We also identified one new haplotype of B. afzelii and three haplotypes of B. burgdorferi isolated from winged specimens of L. cervi. This is the first study to detect the genetic material of B. burgdorferi s.l. in L. cervi in Poland and the first report on the identification of these bacteria in host-seeking specimens in the environment.
Capsaicin Inhibits Multiple Voltage-Gated Ion Channels in Rabbit Ventricular Cardiomyocytes in TRPV1-Independent Manner
Authors: Isaev Dmytro , Yang Keun-Hang Susan , Shabbir Waheed , Howarth Frank Christopher , Oz Murat
Published: September 2022

Capsaicin is a naturally occurring alkaloid derived from chili pepper which is responsible for its hot, pungent taste. It exerts multiple pharmacological actions, including pain-relieving, anti-cancer, anti-inflammatory, anti-obesity, and antioxidant effects. Previous studies have shown that capsaicin significantly affects the contractility and automaticity of the heart and alters cardiovascular functions. In this study, the effects of capsaicin were investigated on voltage-gated ion currents in rabbit ventricular myocytes. Capsaicin inhibited rapidly activated (IKr) and slowly activated (IKs) K+ currents and transient outward (Ito) K+ current with IC50 values of 3.4 µM,14.7 µM, and 9.6 µM, respectively. In addition, capsaicin, at higher concentrations, suppressed voltage-gated Na+ and Ca2+ currents and inward rectifier IK1 current with IC50 values of 42.7 µM, 34.9 µM, and 38.8 µM, respectively. Capsaicin inhibitions of INa, IL-Ca, IKr, IKs, Ito, and IK1 were not reversed in the presence of capsazepine (3 µM), a TRPV1 antagonist. The inhibitory effects of capsaicin on these currents developed gradually, reaching steady-state levels within 3 to 6 min, and the recoveries were usually incomplete during washout. In concentration-inhibition curves, apparent Hill coefficients higher than unity suggested multiple interaction sites of capsaicin on these channels. Collectively, these findings indicate that capsaicin affects cardiac electrophysiology by acting on a diverse range of ion channels and suggest that caution should be exercised when capsaicin is administered to carriers of cardiac channelopathies or to individuals with arrhythmia-prone conditions, such as ischemic heart diseases.
Pretargeted Imaging beyond the Blood–Brain Barrier—Utopia or Feasible?
Authors: Lopes van den Broek Sara , Shalgunov Vladimir , García Vázquez Rocío , Beschorner Natalie , Bidesi Natasha S. R. , Nedergaard Maiken , Knudsen Gitte M. , Sehlin Dag , Syvänen Stina , Herth Matthias M.
Published: September 2022

Pretargeting is a promising nuclear imaging technique that allows for the usage of antibodies (Abs) with enhanced imaging contrast and reduced patient radiation burden. It is based on bioorthogonal chemistry with the tetrazine ligation—a reaction between trans-cyclooctenes (TCOs) and tetrazines (Tzs)—currently being the most popular reaction due to its high selectivity and reactivity. As Abs can be designed to bind specifically to currently ‘undruggable’ targets such as protein isoforms or oligomers, which play a crucial role in neurodegenerative diseases, pretargeted imaging beyond the BBB is highly sought after, but has not been achieved yet. A challenge in this respect is that large molecules such as Abs show poor brain uptake. Uptake can be increased by receptor mediated transcytosis; however, it is largely unknown if the achieved brain concentrations are sufficient for pretargeted imaging. In this study, we investigated whether the required concentrations are feasible to reach. As a model Ab, we used the bispecific anti-amyloid beta (Aβ) anti-transferrin receptor (TfR) Ab 3D6scFv8D3 and conjugated it to a different amount of TCOs per Ab and tested different concentrations in vitro. With this model in hand, we estimated the minimum required TCO concentration to achieve a suitable contrast between the high and low binding regions. The estimation was carried out using pretargeted autoradiography on brain sections of an Alzheimer’s disease mouse model. Biodistribution studies in wild-type (WT) mice were used to correlate how different TCO/Ab ratios alter the brain uptake. Pretargeted autoradiography showed that increasing the number of TCOs as well as increasing the TCO-Ab concentration increased the imaging contrast. A minimum brain concentration of TCOs for pretargeting purposes was determined to be 10.7 pmol/g in vitro. Biodistribution studies in WT mice showed a brain uptake of 1.1% ID/g using TCO-3D6scFv8D3 with 6.8 TCO/Ab. According to our estimations using the optimal parameters, pretargeted imaging beyond the BBB is not a utopia. Necessary brain TCO concentrations can be reached and are in the same order of magnitude as required to achieve sufficient contrast. This work gives a first estimate that pretargeted imaging is indeed possible with antibodies. This could allow the imaging of currently ‘undruggable’ targets and therefore be crucial to monitor (e.g., therapies for intractable neurodegenerative diseases).
Non-Cryoprecipitation Separation of Coagulation FVIII and Prothrombin Complex Proteins by Pseudoaffinity Calcium Elution Chromatography Using Anion Exchange Resin
Authors: Feliciano Gabriel Pinna , Arimori Sara Hayama , Nakao Vinicius Watanabe , Dos Santos Joice Rodrigues , Martins Elizabeth A. L. , Bemquerer Marcelo Porto , Cheng Elisabeth
Published: September 2022

Hemophilia A is treated with human plasma coagulation factor VIII (FVIII) replacement therapy and Hemophilia B with coagulation factor IX, which is purified from prothrombin complex concentrate (PCC). In this paper we evaluated the separation of FVIII and PCC by directly loading raw thawed plasma to an anion exchange resin (AEX). Under this relatively high ionic strength, most of the plasma proteins such as albumin, immunoglobulins and others were not adsorbed. Five resins commonly used in protein purification (plasma fractionation) were tested. With all resins, PCC was eluted by pseudoaffinity in a calcium gradient step. Afterwards, FVIII could be recovered with a good yield and high purification factor in the salt gradient step with 400–500 mM NaCl. Using ANX Sepharose FF and Q Sepharose FF, the CaCl2 elution step was introduced after the intermediate wash with 200 mM NaCl, whereas using DEAE Sepharose FF, Fractogel EMD TMAE and Fractogel EMD DEAD, PCC eluted after the wash of the unbound proteins. Our results indicate that three important fractions: (1) albumin, immunoglobulin etc.; (2) PCC; and (3) FVIII can be separated in one chromatographic AEX column and the delicate and troublesome cryoprecipitation can be eliminated, making the purification of blood products faster and cheaper.
Palmitoleic Acid Acts on Adipose-Derived Stromal Cells and Promotes Anti-Hypertrophic and Anti-Inflammatory Effects in Obese Mice
Authors: Simão Jussara J. , Cruz Maysa M. , Abdala Fernanda M. , Bolsoni-Lopes Andressa , Armelin-Correa Lucia , Alonso-Vale Maria Isabel C.
Published: September 2022

Adipose tissue (AT) secretes adipokines, modulators of low-grade chronic inflammation in obesity. Molecules that induce the emergence of new and functional adipocytes in AT can alleviate or prevent inflammatory and metabolic disorders. The objective of this study was to investigate the role of palmitoleic acid (n7) in 3T3-L1 and primary pre-adipocyte differentiation and AT inflammation. C57BL/6j mice were submitted to a control or high-fat diet (HFD) for 8 weeks, and treated with n7 for 4 weeks. Mice consuming a HFD presented an increase in body weight, epididymal (Epi) fat mass, and Epi adipocytes size. N7 treatment attenuated the body weight gain and completely prevented the hypertrophy of Epi adipocytes, but not the increment in Epi mass induced by the HFD, suggesting a greater adipocytes hyperplasia in animals treated with n7. It was agreed that n7 increased 3T3-L1 proliferation and differentiation, as well as the expression of genes involved in adipogenesis, such as Cebpa, Pparg, aP2, Perilipin, and Scl2a4. Furthermore, n7 decreased the inflammatory cytokines Mcp1, Tnfa, Il6, Cxcl10, and Nos2 genes in Epi vascular stromal cells, but not in the whole AT. These findings show that n7 exerts anti-hypertrophic effects in adipocytes which influence the surrounding cells by attenuating the overexpression of pro-inflammatory cytokines triggered by a HFD.
Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development
Authors: Gkountanas Kostas , Malenović Anđelija , Dotsikas Yannis
Published: September 2022

A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride.
Structurally Modified Bioactive Peptide Inhibits SARS-CoV-2 Lentiviral Particles Expression
Authors: Bhullar Khushwant S. , Nael Manal A. , Elokely Khaled M. , Drews Steven J. , Wu Jianping
Published: September 2022

Coronavirus disease 2019 (COVID-19), the current global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various pharmaceuticals are being developed to counter the spread of the virus. The strategy of repurposing known drugs and bioactive molecules is a rational approach. A previously described molecule, Ile-Arg-Trp (IRW), is a bioactive tripeptide that exhibits an ability to boost angiotensin converting enzyme-2 (ACE2) expression in animals and cells. Given the importance of SARS-CoV-2 S receptor binding domain (RBD)-ACE2 interaction in SARS-CoV-2 pathophysiology, we synthesized various IRW analogs intending to mitigate the RBD-ACE-2 interaction. Herein, we describe two analogs of IRW, A9 (Acetyl-Ile-Arg-Trp-Amide) and A14 (Formyl-Ile-Arg-Trp-Amide) which lowered the SARS-CoV-2 S RBD-ACE2 (at 50 µM) in vitro. The free energy of binding suggested that A9 and A14 interacted with the SARS-CoV-2 S RBD more favorably than ACE2. The calculated MMGBSA ΔG of spike binding for A9 was −57.22 kcal/mol, while that of A14 was −52.44 kcal/mol. A14 also inhibited furin enzymatic activity at various tested concentrations (25, 50, and 100 µM). We confirmed the effect of the two potent analogs using SARS-CoV-2 spike protein overexpressing cells. Both peptides lowered the protein expression of SARS-CoV-2 spike protein at the tested concentration (50 µM). Similarly, both peptides, A9 and A14 (50 µM), also inhibited pseudotyped lentiviral particles with SARS-CoV-2 Spike in ACE2 overexpressing cells. Further, the molecular dynamics (MD) calculations showed the interaction of A9 and A14 with multiple residues in spike S1 RBD. In conclusion, novel peptide analogs of ACE2 boosting IRW were prepared and confirmed through in vitro, cellular, and computational evaluations to be potential seed candidates for SARS-CoV-2 host cell binding inhibition.
Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma
Authors: Chen Yang , Wang Bin , Chen Wenping , Wang Tao , Li Min , Shen Zucheng , Wang Fang , Jia Jing , Li Fenglan , Huang Xiangyu , Zhuang Junyang , Li Ning
Published: September 2022

Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal therapy (PTT) has many outstanding properties, but suffers from poor photostability of photosensitizer and incomplete ablation. Multimodal therapies could combine the advantages of different therapy methods to improve antitumor efficiency. Hence, we designed a nano-delivery system (ICG&DHA@ZIF-8) using zeolitic imidazolate framework-8 (ZIF-8) with a high porous rate and pH sensitivity property, to co-load DHA and indocyanine green (ICG). Dynamic light scattering and transmission electron microscopy were used to characterize the prepared nanoparticles. The photothermal conversion and drug release performances of ICG&DHA@ZIF-8 were investigated. In vitro antitumor efficacy and cellular uptake were studied. The mechanism of the combination treatment was studied by reactive oxygen species level detection and western blot assays. In vivo antitumor assays were then studied with the guidance of ex vivo imaging. The results showed that the ICG&DHA@ZIF-8 based combination therapy could efficiently kill hepatic carcinoma cells and suppress tumor growth. This research provides a potential nanodrug for the treatment of hepatic carcinoma.
Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus
Authors: Mohammadi Tabar Mohadeseh , Khaleghi Moj , Bidram Elham , Zarepour Atefeh , Zarrabi Ali
Published: September 2022

Infectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol (GO-PEG) nano-platform was synthesized and penicillin and oxacillin, two antibiotics that are ineffective against Methicillin-resistant S. aureus (MRSA), were loaded on it to improve their effectiveness. The nanocomposites were characterized using FTIR, XRD, UV–Vis, FE-SEM/EDX, and Zeta potential analyses, followed by an evaluation of their antibacterial activity toward MRSA. Based on the results, drug loaded GO-PEG nanocomposites with loading efficiencies of 81% and 92% for penicillin and oxacillin, respectively, were successfully synthesized. They showed a controlled release within six days. The zeta potential of GO-PEG-oxacillin and penicillin was −13 mV and −11 mV, respectively. The composites showed much more activity against MRSA (80–85% inhibition) in comparison to GO-PEG (almost 0% inhibition) and pure antibiotics (40–45% inhibition). SEM images of MRSA treated with GO-PEG-antibiotics showed a deformation in the structure of bacterial cells, which led to the collapse of their intracellular components. These results demonstrate the effectiveness of utilizing the GO-based nanoplatforms in enhancing the antibacterial activity of the antibiotics.
Characterization and Differential Cytotoxicity of Gramicidin Nanoparticles Combined with Cationic Polymer or Lipid Bilayer
Authors: Pérez-Betancourt Yunys , Zaia Rachel , Evangelista Marina Franchi , Ribeiro Rodrigo Tadeu , Roncoleta Bruno Murillo , Mathiazzi Beatriz Ideriha , Carmona-Ribeiro Ana Maria
Published: September 2022

Gramicidin (Gr) nanoparticles (NPs) and poly (diallyl dimethyl ammonium) chloride (PDDA) water dispersions were characterized and evaluated against Gram-positive and Gram-negative bacteria and fungus. Dynamic light scattering for sizing, zeta potential analysis, polydispersity, and colloidal stability over time characterized Gr NPs/PDDA dispersions, and plating and colony-forming units counting determined their microbicidal activity. Cell viabilities of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans in the presence of the combinations were reduced by 6, 7, and 7 logs, respectively, at 10 μM Gr/10 μg·mL−1 PDDA, 0.5 μM Gr/0. 5μg·mL−1 PDDA, and 0.5 μM Gr/0.5 μg·mL−1 PDDA, respectively. In comparison to individual Gr doses, the combinations reduced doses by half (S. aureus) and a quarter (C. albicans); in comparison to individual PDDA doses, the combinations reduced doses by 6 times (P. aeruginosa) and 10 times (C. albicans). Gr in supported or free cationic lipid bilayers reduced Gr activity against S. aureus due to reduced Gr access to the pathogen. Facile Gr NPs/PDDA disassembly favored access of each agent to the pathogen: PDDA suctioned the pathogen cell wall facilitating Gr insertion in the pathogen cell membrane. Gr NPs/PDDA differential cytotoxicity suggested the possibility of novel systemic uses for the combination.
Binding and Kinetic Analysis of Human Protein Phosphatase PP2A Interactions with Caspase 9 Protein and the Interfering Peptide C9h
Authors: Dorgham Karim , Murail Samuel , Tuffery Pierre , Savier Eric , Bravo Jeronimo , Rebollo Angelita
Published: September 2022

The serine/threonine phosphatase PP2A and the cysteine protease Caspase 9 are two proteins involved in physiological and pathological processes, including cancer and apoptosis. We previously demonstrated the interaction between Caspase 9 and PP2A and identified the C9h peptide, corresponding to the binding site of Caspase 9 to PP2A. This interfering peptide can modulate Caspase 9/PP2A interaction leading to a strong therapeutic effect in vitro and in vivo in mouse models of tumor progression. In this manuscript, we investigate (I) the peptide binding to PP2A combining docking with molecular dynamics and (II) the secondary structure of the peptide using CD spectroscopy. Additionally, we compare the binding affinity, using biolayer interferometry, of the wild-type protein PP2A with Caspase 9 and vice versa to that observed between the PP2A protein and the interfering peptide C9h. This result strongly encourages the use of peptides as new therapeutics against cancer, as shown for the C9h peptide already in clinical trial.
Extracts of Rheum palmatum and Aloe vera Show Beneficial Properties for the Synergistic Improvement of Oral Wound Healing
Authors: Müller-Heupt Lena Katharina , Wiesmann Nadine , Schröder Sofia , Korkmaz Yüksel , Vierengel Nina , Groß Jonathan , Dahm Rolf , Deschner James , Opatz Till , Brieger Juergen , Al-Nawas Bilal , Kämmerer Peer W.
Published: September 2022

Various local and systemic factors compromise oral wound healing and may lead to wound dehiscence, inflammation, or ulcers. Currently, there is a lack of topical therapeutical options. Thus, this study aimed to investigate the effect of Aloe vera (AV) and Rheum palmatum root (RPR) on oral wound healing capacity in vitro. The effect of AV and RPR on human primary fibroblast viability and migration was studied by measuring metabolic activity and gap closure in a scratch assay. Furthermore, cell cycle distribution and cytoskeletal features were analyzed. Antimicrobial activity against the oral pathogen Porphyromonas gingivalis was evaluated by broth microdilution assay. AV and RPR increased fibroblast migration after single agent treatment. Synergistic effects of the plant extract combination were observed regarding cellular migration which were confirmed by calculation of the phenomenological combination index (pCI), whereas the cell cycle distribution was not influenced. Furthermore, the combination of AV and RPR showed synergistic antibacterial effects as determined by the fractional inhibitory concentration index. This study demonstrated that the combination of AV and RPR can promote the migration of human primary fibroblasts in vitro and exert antimicrobial efficacy against P. gingivalis, suggesting these compounds for the topical treatment of wound healing disorders.
Effect of Primary Packaging Material on the Stability Characteristics of Diazepam and Midazolam Parenteral Formulations
Authors: Rodríguez Fernández María José , Serrano Lopez Dolores Remedios , Torrado Juan José
Published: September 2022

Diazepam and midazolam are formulated in autoinjectors for parenteral administration to decrease seizures in the case of emergency. However, the compatibility of these lipophilic drugs with the primary packaging material is a key part of drug formulation development. In this work, diazepam and midazolam were packaged in glass syringes as parenteral solutions using two different elastomeric sealing materials (PH 701/50 C BLACK and 4023/50 GRAY). Syringes were stored at three different storage temperatures: 4, 25, and 40 °C. At different time points over 3 years, physical appearance, benzodiazepine sorption on the sealing elastomeric materials, and drug content in solution were assayed. A detailed study on the adsorption profile of both benzodiazepines on the elastomeric gaskets was performed, indicating that the novel rubber material made of bromobutyl derivatives (4023/50 GRAY) is a better choice for manufacturing autoinjectors due to lower drug adsorption. Diazepam showed a better stability profile than midazolam, with the latter solubilised as a hydrochloride salt in an acidic pH that can affect the integrity of the elastomer over time. The amount of drug adsorbed on the surface of the elastomer was measured by NIR and correlated using chemometric models with the amount retained in the elastomeric gaskets quantified by HPLC.
Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones
Authors: Mármol Inés , Quero Javier , Azcárate Paula , Atrián-Blasco Elena , Ramos Carla , Santos Joana , Gimeno María Concepción , Rodríguez-Yoldi María Jesús , Cerrada Elena
Published: September 2022

In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.
Detection Optimization of an Optically Trapped Microparticle in Vacuum with Kalman Filter
Authors: Xu Shidong , Chen Ming , Yang Jianyu , Chen Xingfan , Li Nan , Hu Huizhu
Published: September 2022

The optical trapping of micro-nano particles in a high vacuum has become a popular research platform in various frontier fields of physics because of its excellent isolation from the environment. The precise measurement of particle motion information is required to analyze and control particle motion modes in traps. However, the detection accuracy is limited by measurement noise and coupling signals from other axes in microparticle optical traps. In this study, we use the Kalman filter to extract the real motion information of each axis under simulation conditions, and the results show that the Kalman filter performs well in noise suppression, improving the RMSE from 12.64 to 5.18 nm and enhancing the feedback cooling performance by approximately 27% through reducing the axes’ signal coupling ratio. We believe that as a solution to these challenges, the Kalman filter will bring a significant achievement to micrometer particle optical traps in vacuums.
Effect of the Number of Dark Days and Planting Density on the Health-Promoting Phytochemicals and Antioxidant Capacity of Mustard (Brassica juncea) Sprouts
Authors: Li Zhiqing , Di Hongmei , Cheng Wenjuan , Ren Guanru , Zhang Yi , Ma Jie , Ma Wei , Yang Jiao , Lian Huashan , Li Xiaomei , Huang Zhi , Tang Yi , Zheng Yangxia , Li Huanxiu , Zhang Fen , Sun Bo
Published: September 2022

Mustard is an edible vegetable in the genus Brassica with tender and clean sprouts and short growth cycles that has become a rich source of nutrients required by humans. Here, the effects of dark exposure duration and planting density on the health-promoting phytochemicals and the antioxidant capacity of mustard sprouts were evaluated. The content of soluble sugar, soluble protein, chlorophyll, and carotenoids and the antioxidant capacity of mustard were higher in the two-day dark treatment; the content of indolic glucosinolates was also more affected in the dark day experiment than in the planting density experiment. The soluble sugar, soluble protein, and aliphatic and total glucosinolate levels were higher when sprouts were grown at high densities (6–7 g per tray); however, no significant variation was observed in the content of chlorophyll and carotenoids and the antioxidant capacity. The results of this study show that the optimum cultivation regime for maximizing the concentrations of nutrients of mustard plants is a planting density of 6 g of seeds per tray and a two-day dark treatment.
Resistance to Snow Mold as a Target Trait for Rye Breeding
Authors: Ponomareva Mira , Gorshkov Vladimir , Ponomarev Sergey , Mannapova Gulnaz , Askhadullin Danil , Askhadullin Damir , Gogoleva Olga , Meshcherov Azat , Korzun Viktor
Published: September 2022

Winter rye is a versatile crop widely used for food and industry. Although rye is resistant to abiotic stressors and many phytopathogens, it is severely damaged by pink snow mold (SM)—a progressive disease caused by the psychrotolerant fungus Microdochium nivale under the snow cover or during prolonged periods of wet and cool conditions. Due to little use of the SM resistance sources in contemporary breeding, varieties with at least moderate resistance to SM are limited. Our study aimed to integrate field assessment under natural conditions and an artificially enriched infection background with laboratory techniques for testing rye accessions and selecting SM resistant sources for applied breeding programs and genetic research. We revealed valuable sources of SM resistance and split rye accessions, according to the level of the genetic divergence of the SM resistance phenotype. This allowed us to select the most distinct donors of the SM resistance, for their use as parental forms, to include novel variability sources in the breeding program for achieving high genetic variability, as well as enhanced and durable SM resistance, in progeny. The rye accessions analyzed here, and the suggested options for their use in breeding, are valuable tools for rye breeding.
Physiological and Transcriptomic Analyses Reveal the Mechanisms of Compensatory Growth Ability for Early Rice after Low Temperature and Weak Light Stress
Authors: Wang Hui , Zhong Lei , Fu Xiaoquan , Huang Shiying , Fu Haihui , Shi Xiang , Hu Lifang , Cai Yicong , He Haohua , Chen Xiaorong
Published: September 2022

“Late spring coldness” (T) is a frequent meteorological disaster in the spring in southern China, often causing severe yield losses of direct-seeded early rice. In this study, we investigated the mechanisms underlying the differences in the compensatory growth ability of different rice genotypes by focusing on agronomic traits, physiological indicators, and transcriptome. The results showed that there were significant differences in the compensatory growth recovery ability of different genotypes after a combination of four days of low temperature and weak light stress. Only the strong compensatory growth genotype B116 was able to grow rapidly and reduce soluble protein and H2O2 concentrations rapidly after stress. By analyzing enzyme activity as well as endogenous hormone concentration, we found that the high superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and high levels of abscisic acid (ABA) could reduce the damage of B116 during stress. Meanwhile, higher glutamine synthetase (GS) and nitrate reductase (NR) activity and higher levels of gibberellin A3(GA3), indoleacetic acid (IAA), and zeatin nucleoside (ZR) could enable B116 to grow rapidly after stress. The identified differentially expressed genes (DEGs) indicated that there were large differences in POD-related genes and gibberellin metabolism between B116 and B144 after stress; RT-PCR quantification also showed a trend consistent with RNA-seq, which may be an important reason for the differences in compensatory growth ability.
Silicon Supplementation Alleviates the Salinity Stress in Wheat Plants by Enhancing the Plant Water Status, Photosynthetic Pigments, Proline Content and Antioxidant Enzyme Activities
Authors: Singh Pooja , Kumar Vikram , Sharma Jyoti , Saini Sakshi , Sharma Priyanka , Kumar Sandeep , Sinhmar Yogesh , Kumar Dhirendra , Sharma Asha
Published: September 2022

Silicon (Si) is the most abundant element on earth after oxygen and is very important for plant growth under stress conditions. In the present study, we inspected the role of Si in the mitigation of the negative effect of salt stress at three concentrations (40 mM, 80 mM, and 120 mM NaCl) in two wheat varieties (KRL-210 and WH-1105) with or without Si (0 mM and 2 mM) treatment. Our results showed that photosynthetic pigments, chlorophyll stability index, relative water content, protein content, and carbohydrate content were reduced at all three salt stress concentrations in both wheat varieties. Moreover, lipid peroxidation, proline content, phenol content, and electrolyte leakage significantly increased under salinity stress. The antioxidant enzyme activities, like catalase and peroxidase, were significantly enhanced under salinity in both leaves and roots; however, SOD activity was drastically decreased under salt stress in both leaves and roots. These negative effects of salinity were more pronounced in WH-1105, as KRL-210 is a salt-tolerant wheat variety. On the other hand, supplementation of Si improved the photosynthetic pigments, relative water, protein, and carbohydrate contents in both varieties. In addition, proline content, MDA content, and electrolyte leakage were shown to decline following Si application under salt stress. It was found that applying Si enhanced the antioxidant enzyme activities under stress conditions. Si showed better results in WH-1105 than in KRL-210. Furthermore, Si was found to be more effective at a salt concentration of 120 mM compared to low salt concentrations (40 mM, 80 mM), indicating that it significantly improved plant growth under stressed conditions. Our experimental findings will open a new area of research in Si application for the identification and implication of novel genes involved in enhancing salinity tolerance.
Evaluation of Trigonella foenum-graecum L. Plant Food Safety after Lead Exposure: Phytochemical Processes
Authors: Mnafgui Wiem , Rizzo Valeria , Muratore Giuseppe , Hajlaoui Hicham , Elleuch Amine
Published: September 2022

Lead stands as a food contaminant through its accumulation in consumed plants. In this study, the effects of lead (II) chloride (PbCl2) and its levels of uptake on morphological and phytochemical responses of fenugreek were assessed to evaluate its tolerance and safety for human consumption. Results revealed that PbCl2 (50–2000 mg L−1) did not affect the germination rate, but it decreased the radicle length and amylase activity. After three months of Pb treatments, the elemental analysis showed that Pb accumulation was greater in roots than shoots, and it was not present in harvested seeds. The bioaccumulation factor > 1 and the translocation factor << 1 observed for 1000 mg L−1 PbCl2 suggested appropriateness of fenugreek as a phytostabilizer. Additionally, increased lipid peroxidation, hydrogen peroxide, flavonoid levels and catalase activity were observed in Pb-treated fenugreek. Meanwhile, decreased chlorophyll content was detected under these conditions. In turn, the total phenol was correlated with Pb treatment only in roots. HPLC analysis proved that under Pb stress, gallic acid was the most produced compound in treated roots compared to shoots, followed by quercetin. Syringic and chlorogenic acids were more produced in shoots. In conclusion, fenugreek can be used for Pb phytoremediation and is safe for consumption after Pb treatments in the traditional medicine system.
Alchemilla monticola Opiz. Functional Traits Respond to Diverse Alpine Environmental Conditions in Karavanke, Slovenia
Authors: Trošt Sedej Tadeja , Turk Tajda
Published: September 2022

Alpine plants are exposed to demanding environmental conditions, such as high ultraviolet (UV) and photosynthetic radiation, extreme temperatures, drought, and nutrient deficiencies. Alpine plants adapt and acclimate to harsh conditions, developing several strategies, including biochemical, physiological, and optical responses. However, alpine plants’ survival strategies are hardly researched due to time-consuming and complex experimental conditions, which are supported by scarce studies. Our study focused on the functional traits of the alpine plant Alchemilla monticola Opiz (hairy lady’s mantle) growing at two different altitudes (1500, 2000 m a.s.l.) and two different UV exposures per altitude. Near-ambient (UV) and reduced (UV-) UV radiations were provided by using two sorts of UV absorbing filters; temperatures were monitored hourly. The experimental plots were located at Tegoška Gora, Karavanke, Slovenia. Functional traits: physiological, biochemical, and optical characteristics were recorded three times during the growing season. A. monticola showed high maximum photochemical efficiency at both altitudes throughout the season, which confirms good adaptation and acclimatization of the plant. Furthermore, significantly higher maximum photochemical efficiency at the subalpine altitude coincided with significantly higher UV absorbing compounds (UV AC) contents at the subalpine compared to the montane altitude in August. A. monticola manifested high UV AC contents throughout the season, with significantly increased synthesis of UV AC contents in the subalpine conditions in August and September. The stomatal conductance rate increased with altitude and was correlated mostly to a lower temperature. A. monticola leaves did not transmit any UV spectrum, which corresponded to high total UV AC contents. The leaf transmittance of the photosynthetic spectrum increased at the subalpine altitude, while the transmittance of the green and yellow spectra increased under the reduced UV radiation in the autumn. A. monticola’s high photosynthetic spectrum transmittance at the subalpine altitude in the autumn might therefore be due to subalpine harsh environmental conditions, as well as plant ontogenetical phase.
Edible Flower Species as a Promising Source of Specialized Metabolites
Authors: Dujmović Mia , Radman Sanja , Opačić Nevena , Fabek Uher Sanja , Mikuličin Vida , Voća Sandra , Šic Žlabur Jana
Published: September 2022

Eating habits are changing over time and new innovative nutrient-rich foods will play a great role in the future. Awareness of the importance of a healthy diet is growing, so consumers are looking for new creative food products rich in phytochemicals, i.e., specialized metabolites (SM). The consumption of fruits, vegetables and aromatic species occupies an important place in the daily diet, but different edible flower species are still neglected and unexplored. Flowers are rich in SM, have strong antioxidant capacities and also possess significant functional and biological values with favorable impacts on human health. The main aim of this study was to evaluate the content of SM and the antioxidant capacities of the edible flower species: Calendula officinalis L. (common marigold), Tagetes erecta L. (African marigold), Tropaeolum majus L. (nasturtium), Cucurbita pepo L. convar. giromontiina (zucchini) and Centaurea cyanus L. (cornflower). The obtained results showed the highest content of ascorbic acid (129.70 mg/100 g fw) and anthocyanins (1012.09 mg/kg) recorded for cornflower, phenolic compounds (898.19 mg GAE/100 g fw) and carotenoids (0.58 mg/g) for African marigold and total chlorophylls (0.75 mg/g) for common marigold. In addition to the esthetic impression of the food, they represent an important source of SM and thus can have a significant impact if incorporated in the daily diet.