bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal and Early Life Exposure to the Danish Mandatory Vitamin D Fortification Policy Might Prevent Inflammatory Bowel Disease Later in Life: A Societal Experiment
Authors: Duus Katrine S. , Moos Caroline , Frederiksen Peder , Andersen Vibeke , Heitmann Berit L.
Published: April 2021

This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 (95% CI: 0.79; 0.95). No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age.
Effects of Lactobacillus plantarum CJLP55 on Clinical Improvement, Skin Condition and Urine Bacterial Extracellular Vesicles in Patients with Acne Vulgaris: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Kim Mi-Ju , Kim Kun-Pyo , Choi Eunhye , Yim June-Hyuck , Choi Chunpil , Yun Hyun-Sun , Ahn Hee-Yoon , Oh Ji-Young , Cho Yunhi
Published: April 2021

Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.
Interferon Gamma Inhibits Equine Herpesvirus 1 Replication in a Cell Line-Dependent Manner
Authors: Kim Seong K. , Shakya Akhalesh K. , O’Callaghan Dennis J.
Published: April 2021

The sole equine herpesvirus 1 (EHV-1) immediate-early protein (IEP) is essential for viral replication by transactivating viral immediate-early (IE), early (E), and late (L) genes. Here, we report that treatment of mouse MH-S, equine NBL6, and human MRC-5 cells with 20 ng/mL of IFN-γ reduced EHV-1 yield by 1122-, 631-, and 10,000-fold, respectively. However, IFN-γ reduced virus yield by only 2–4-fold in mouse MLE12, mouse L-M, and human MeWo cells compared to those of untreated cells. In luciferase assays with the promoter of the EHV-1 early regulatory EICP0 gene, IFN-γ abrogated trans-activation activity of the IEP by 96% in MH-S cells, but only by 21% in L-M cells. Similar results were obtained in assays with the early regulatory UL5 and IR4 promoter reporter plasmids. IFN-γ treatment reduced IEP protein expression by greater than 99% in MH-S cells, but only by 43% in L-M cells. The expression of IEP and UL5P suppressed by IFN-γ was restored by JAK inhibitor treatment, indicating that the inhibition of EHV-1 replication is mediated by JAK/STAT1 signaling. These results suggest that IFN-γ blocks EHV-1 replication by inhibiting the production of the IEP in a cell line-dependent manner. Affymetrix microarray analyses of IFN-γ-treated MH-S and L-M cells revealed that five antiviral ISGs (MX1, SAMHD1, IFIT2, NAMPT, TREX1, and DDX60) were upregulated 3.2–18.1-fold only in MH-S cells.
Seroprevalence and Risk Factors Associated with Chlamydia abortus Infection in Sheep and Goats in Eastern Saudi Arabia
Authors: Fayez Mahmoud , Elmoslemany Ahmed , Alorabi Mohammed , Alkafafy Mohamed , Qasim Ibrahim , Al-Marri Theeb , Elsohaby Ibrahim
Published: April 2021

Chlamydia abortus (C. abortus) is intracellular, Gram-negative bacterium that cause enzootic abortion in sheep and goats. Information on C. abortus seroprevalence and flock management risk factors associated with C. abortus seropositivity in sheep and goats in Saudi Arabia are scarce. The objectives of this study were to (i) estimate the animal, flock, and within-flock seroprevalence of C. abortus among Eastern Province sheep and goat flocks and (ii) identify the flock management and animal risk factors associated with C. abortus seropositivity in Eastern Province, Saudi Arabia. A cross-sectional study with a two-stage sampling process was carried out in the Eastern Province, Saudi Arabia, between 2015 and 2016. A total of 1717 sheep and 1101 goat serum samples were collected from 21 sheep and 14 goat flocks, then were tested for C. abortus antibodies using a commercial ELISA Kit. In addition, vaginal swabs and aborted tissue samples were collected from sheep (n = 48) and goats (n = 15) with recent history of abortion for detection of C. abortuspmp gene using PCR. A questionnaire was constructed to collect information about flock management and animal risk factors possibly associated with C. abortus infection in sheep and goats. The true sheep and goat-level seroprevalences were 11.1% (95% CI: 9.7–12.7) and 10.6% (95% CI: 8.8–12.5), respectively. The true flock-level seroprevalence was 100% for both sheep and goats. However, the average within sheep and goat flocks true seroprevalences were 9.6% (95% CI: 1.8–22.9) and 9.3% (95% CI: 1.8–19.5), respectively. Multivariable logistic regression revealed that introduction of new sheep to the flocks (OR = 2.6; 95% CI: 1.5–4.4), type of breeding system (OR = 1.8; 95% CI: 1.0–3.4), flocks allowing females in (OR = 1.9; 95% CI: 1.1–3.3) or females out (OR = 2.2; 95% CI: 1.1–4.3), and sheep age 1.4–2.8 years (OR = 1.9; 95% CI: 1.3–2.9) were potential risk factors for C. abortus seropositivity in sheep flocks. However, in goat flocks, the introduction of new goats to the flocks (OR: 1.9; 95% CI: 1.2–3.0) was identified as a risk factor, whereas good farm hygiene (OR: 0.3; 95% CI: 0.2–0.7) was identified as a protective factor. C. abortus pmp gene was identified in 45 (93.8%) and 15 (100%) of samples collected from sheep and goats, respectively. These results could be used to implement efficient management measures to prevent and control C. abortus infection in sheep and goats in Eastern Province, Saudi Arabia, but also could be used to reduce the risk of C. abortus infection in sheep and goat flocks with similar management practices in other regions.
High Biofilm Formation of Non-Smooth Candida parapsilosis Correlates with Increased Incorporation of GPI-Modified Wall Adhesins
Authors: Moreno-Martínez Ana Esther , Gómez-Molero Emilia , Sánchez-Virosta Pablo , Dekker Henk L. , de Boer Albert , Eraso Elena , Bader Oliver , de Groot Piet W. J.
Published: April 2021

Candida parapsilosis is among the most frequent causes of candidiasis. Clinical isolates of this species show large variations in colony morphotype, ranging from round and smooth to a variety of non-smooth irregular colony shapes. A non-smooth appearance is related to increased formation of pseudohyphae, higher capacity to form biofilms on abiotic surfaces, and invading agar. Here, we present a comprehensive study of the cell wall proteome of C. parapsilosis reference strain CDC317 and seven clinical isolates under planktonic and sessile conditions. This analysis resulted in the identification of 40 wall proteins, most of them homologs of known Candida albicans cell wall proteins, such as Gas, Crh, Bgl2, Cht2, Ecm33, Sap, Sod, Plb, Pir, Pga30, Pga59, and adhesin family members. Comparative analysis of exponentially growing and stationary phase planktonic cultures of CDC317 at 30 °C and 37 °C revealed only minor variations. However, comparison of smooth isolates to non-smooth isolates with high biofilm formation capacity showed an increase in abundance and diversity of putative wall adhesins from Als, Iff/Hyr, and Hwp families in the latter. This difference depended more strongly on strain phenotype than on the growth conditions, as it was observed in planktonic as well as biofilm cells. Thus, in the set of isolates analyzed, the high biofilm formation capacity of non-smooth C. parapsilosis isolates with elongated cellular phenotypes correlates with the increased surface expression of putative wall adhesins in accordance with their proposed cellular function.
Design, Synthesis, Biological Evaluation and In Silico Studies of Pyrazole-Based NH2-Acyl Oseltamivir Analogues as Potent Neuraminidase Inhibitors
Authors: Ye Jiqing , Lin Lin , Xu Jinyi , Chan Paul Kay-sheung , Yang Xiao , Ma Cong
Published: April 2021

Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.
Screening of Benzimidazole-Based Anthelmintics and Their Enantiomers as Repurposed Drug Candidates in Cancer Therapy
Authors: Florio Rosalba , Carradori Simone , Veschi Serena , Brocco Davide , Di Genni Teresa , Cirilli Roberto , Casulli Adriano , Cama Alessandro , De Lellis Laura
Published: April 2021

Repurposing of approved non-antitumor drugs represents a promising and affordable strategy that may help to increase the repertoire of effective anticancer drugs. Benzimidazole-based anthelmintics are antiparasitic drugs commonly employed both in human and veterinary medicine. Benzimidazole compounds are being considered for drug repurposing due to antitumor activities displayed by some members of the family. In this study, we explored the effects of a large series of benzimidazole-based anthelmintics (and some enantiomerically pure forms of those containing a stereogenic center) on the viability of different tumor cell lines derived from paraganglioma, pancreatic and colorectal cancer. Flubendazole, parbendazole, oxibendazole, mebendazole, albendazole and fenbendazole showed the most consistent antiproliferative effects, displaying IC50 values in the low micromolar range, or even in the nanomolar range. In silico evaluation of their physicochemical, pharmacokinetics and medicinal chemistry properties also provided useful information related to the chemical structures and potential of these compounds. Furthermore, in view of the potential repurposing of these drugs in cancer therapy and considering that pharmaceutically active compounds may have different mechanisms of action, we performed an in silico target prediction to assess the polypharmacology of these benzimidazoles, which highlighted previously unknown cancer-relevant molecular targets.
Evaluation of the Expression Profile of Irinotecan-Induced Diarrhea in Patients with Colorectal Cancer
Authors: Okunaka Mashiro , Kano Daisuke , Matsui Reiko , Kawasaki Toshikatsu , Uesawa Yoshihiro
Published: April 2021

Irinotecan (CPT-11) is widely used for the treatment of unresectable colorectal cancer in combination with fluoropyrimidines, such as 5-fluorouracil and S-1. Diarrhea is one of the adverse effects associated with CPT-11 and frequently reported by patients treated with CPT-11-containing regimens combined with oral fluoropyrimidines. However, the mechanisms involved in this process, as well as whether fluctuations in the frequency and differences in the onset time of diarrhea with each CPT-11-containing regimen are caused by drug interactions remain unclear. Therefore, we examined the incidence of diarrhea caused by each CPT-11-containing regimen in patients with colorectal cancer using data from the large voluntary reporting Japanese Adverse Drug Event Report (JADER) database. Firstly, we searched for suspected drugs related to the occurrence of diarrhea using reported odds ratio and calculated the signal score to assess drug–drug interactions. Subsequently, we conducted a time-to-onset analysis using Weibull distribution. The results showed that the combination of CPT-11 with S-1 increased the frequency of diarrhea due to a pharmacological interaction but delayed its onset. The present results may contribute to the appropriate management of drug-induced adverse effects by healthcare professionals.
Aminoalkylamides of Eremomycin Exhibit an Improved Antibacterial Activity
Authors: Moiseenko Elena I. , Erdei Réka , Grammatikova Natalia E. , Mirchink Elena P. , Isakova Elena B. , Pereverzeva Eleonora R. , Batta Gyula , Shchekotikhin Andrey E.
Published: April 2021

After decades, the glycopeptide vancomycin is still the preferred antibiotic against resistant strains of Gram-positive bacteria. Although its clinical use is strictly regulated, the gradual spread of vancomycin-resistant bacteria, such as glycopeptide-resistant and glycopeptide-intermediate Staphylococcus aureus and vancomycin-resistant Enterococcus spp., is a serious health problem. Based on the literature data and previous studies, our main goal was to assess the antimicrobial potential and to study the structure–activity relationship of new eremomycin aminoalkylamides. We designed and synthesized a series of new eremomycin amides in which eremomycin is conjugated with a hydrophobic arylalkyl group via an alkylenediamine spacer, and tested their antibacterial activities on a panel of Gram-positive strains that were sensitive and resistant to a “gold-standard” vancomycin. Based on the data obtained, the structure–activity relationships were investigated, and a lead compound was selected for in-depth testing. Research carried out using an in vivo model of staphylococcus sepsis, acute toxicity studies, and the estimated therapeutic index also showed the advantage of the selected eremomycin amide derivative in particular, as well as the chosen direction in general.
Ensuring Homogeneity in Powder Mixtures for Pharmaceuticals and Dietary Supplements: Evaluation of a 3-Axis Mixing Equipment
Authors: Marianni Bruna , Polonini Hudson , Oliveira Marcone A.L.
Published: April 2021

The mixing process plays a pivotal role in the quality of pharmaceuticals and food/dietary supplements, as it can impact the homogeneity of the substances in their dosage form and affect characteristics such as dissolution and stability. Thus, the choice of the right mixing device is paramount for compounding pharmacies. In this paper, we evaluated the mixing efficacy of a new 3-axis mixer device and determined its optimal working conditions. Three different formulations were compounded with the device and a total of 540 individual assays were performed by HPLC or ICP-MS to validate its use, in addition to a direct comparison among it and two alternative mixing methods. The 3-axis mixer device was able to provide homogeneous mixtures and finished capsules with adequate content uniformity with a broad range of conditions of use (mixing times from 2 to 8 min, and speed of rotation from 10 to 100 rpm). In addition, the device was superior to classical mixing methods (such as the use of manually shaken plastic bags) and at least equivalent to well-established ones (Y-shaped mixer). Finally, we proposed a cleaning procedure that was also adequate to prevent cross-contamination among products compounded with the same device.
Hybrid 3D Printing of Advanced Hydrogel-Based Wound Dressings with Tailorable Properties
Authors: Milojević Marko , Harih Gregor , Vihar Boštjan , Vajda Jernej , Gradišnik Lidija , Zidarič Tanja , Stana Kleinschek Karin , Maver Uroš , Maver Tina
Published: April 2021

Despite the extensive utilization of polysaccharide hydrogels in regenerative medicine, current fabrication methods fail to produce mechanically stable scaffolds using only hydrogels. The recently developed hybrid extrusion-based bioprinting process promises to resolve these current issues by facilitating the simultaneous printing of stiff thermoplastic polymers and softer hydrogels at different temperatures. Using layer-by-layer deposition, mechanically advantageous scaffolds can be produced by integrating the softer hydrogel matrix into a stiffer synthetic framework. This work demonstrates the fabrication of hybrid hydrogel-thermoplastic polymer scaffolds with tunable structural and chemical properties for applications in tissue engineering and regenerative medicine. Through an alternating deposition of polycaprolactone and alginate/carboxymethylcellulose gel strands, scaffolds with the desired architecture (e.g., filament thickness, pore size, macro-/microporosity), and rheological characteristics (e.g., swelling capacity, degradation rate, and wettability) were prepared. The hybrid fabrication approach allows the fine-tuning of wettability (approx. 50–75°), swelling (approx. 0–20× increased mass), degradability (approx. 2–30+ days), and mechanical strength (approx. 0.2–11 MPa) in the range between pure hydrogels and pure thermoplastic polymers, while providing a gradient of surface properties and good biocompatibility. The controlled degradability and permeability of the hydrogel component may also enable controlled drug delivery. Our work shows that the novel hybrid hydrogel-thermoplastic scaffolds with adjustable characteristics have immense potential for tissue engineering and can serve as templates for developing novel wound dressings.
Development, Characterization, and Ex Vivo Assessment of Elastic Liposomes for Enhancing the Buccal Delivery of Insulin
Authors: Bashyal Santosh , Seo Jo-Eun , Keum Taekwang , Noh Gyubin , Lamichhane Shrawani , Lee Sangkil
Published: April 2021

Buccal drug delivery is a suitable alternative to invasive routes of drug administration. The buccal administration of insulin for the management of diabetes has received substantial attention worldwide. The main aim of this study was to develop and characterize elastic liposomes and assess their permeability across porcine buccal tissues. Sodium-cholate-incorporated elastic liposomes (SC-EL) and sodium-glycodeoxycholate-incorporated elastic liposomes (SGDC-EL) were prepared using the thin-film hydration method. The prepared liposomes were characterized and their ex vivo permeability attributes were investigated. The distribution of the SC-EL and SGDC-EL across porcine buccal tissues was evaluated using confocal laser scanning microscopy (CLSM). The SGDC-EL were the most superior nanocarriers since they significantly enhanced the permeation of insulin across porcine buccal tissues, displaying a 4.33-fold increase in the permeability coefficient compared with the insulin solution. Compared with the SC-EL, the SGDC-EL were better at facilitating insulin permeability, with a 3.70-fold increase in the permeability coefficient across porcine buccal tissue. These findings were further corroborated based on bioimaging analysis using CLSM. SGDC-ELs showed the greatest fluorescence intensity in buccal tissues, as evidenced by the greater shift of fluorescence intensity toward the inner buccal tissue over time. The fluorescence intensity ranked as follows: SGDC-EL > SC-EL > FITC–insulin solution. Conclusively, this study highlighted the potential nanocarriers for enhancing the buccal permeability of insulin.
Mesoporous Silica Nanoparticles: Properties and Strategies for Enhancing Clinical Effect
Authors: Frickenstein Alex N. , Hagood Jordan M. , Britten Collin N. , Abbott Brandon S. , McNally Molly W. , Vopat Catherine A. , Patterson Eian G. , MacCuaig William M. , Jain Ajay , Walters Keisha B. , McNally Lacey R.
Published: April 2021

Due to the theragnostic potential of mesoporous silica nanoparticles (MSNs), these were extensively investigated as a novel approach to improve clinical outcomes. Boasting an impressive array of formulations and modifications, MSNs demonstrate significant in vivo efficacy when used to identify or treat myriad malignant diseases in preclinical models. As MSNs continue transitioning into clinical trials, a thorough understanding of the characteristics of effective MSNs is necessary. This review highlights recent discoveries and advances in MSN understanding and technology. Specific focus is given to cancer theragnostic approaches using MSNs. Characteristics of MSNs such as size, shape, and surface properties are discussed in relation to effective nanomedicine practice and projected clinical efficacy. Additionally, tumor-targeting options used with MSNs are presented with extensive discussion on active-targeting molecules. Methods for decreasing MSN toxicity, improving site-specific delivery, and controlling release of loaded molecules are further explained. Challenges facing the field and translation to clinical environments are presented alongside potential avenues for continuing investigations.
BSA-Silver Nanoparticles: A Potential Multimodal Therapeutics for Conventional and Photothermal Treatment of Skin Cancer
Authors: Kim Dasom , Amatya Reeju , Hwang Seungmi , Lee Sumi , Min Kyoung Ah , Shin Meong Cheol
Published: April 2021

Silver nanoparticles (NPs) have attracted a considerable interest in the field of cancer research due to their potential utility in cancer therapy. In the present study, we developed bovine serum albumin (BSA)-coated silver NPs (BSA-Silver NPs) and characterized in vitro multimodal therapeutic activities of NPs for the treatment of skin cancer. BSA-Silver NPs were synthesized by a single-step reduction process, and the successful preparation was verified through a list of physical characterizations, including transmission electron microscopy (TEM), ultraviolet-visible (UV–VIS) light spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) spectroscopy. The synthesized BSA-Silver NPs showed marked cytocidal effects on B16F10 melanoma cells, which was likely caused by oxidative stress. BSA-Silver NPs also elicited significant anti-angiogenic effects on HUVEC (human umbilical vein endothelial cell) by inhibiting their proliferation, migration, and tube formation. Moreover, BSA-Silver NPs showed a considerable light-to-heat conversion ability, suggesting their utility as photothermal agents. Overall, our findings suggest that BSA-Silver NPs may be promising candidates for the multimodal therapy of skin cancer.
In Silico Selection and Evaluation of Pugnins with Antibacterial and Anticancer Activity Using Skin Transcriptome of Treefrog (Boana pugnax)
Authors: Liscano Yamil , Medina Laura , Oñate-Garzón Jose , Gúzman Fanny , Pickholz Monica , Delgado Jean Paul
Published: April 2021

In order to combat bacterial and cancer resistance, we identified peptides (pugnins) with dual antibacterial l–anticancer activity from the Boana pugnax (B. pugnax) skin transcriptome through in silico analysis. Pugnins A and B were selected owing to their high similarity to the DS4.3 peptide, which served as a template for their alignment to the B. pugnax transcriptome, as well as their function as part of a voltage-dependent potassium channel protein. The secondary peptide structure stability in aqueous medium was evaluated as well, and after interaction with the Escherichia coli (E. coli) membrane model using molecular dynamics. These pugnins were synthesized via solid-phase synthesis strategy and verified by Reverse phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry. Subsequently, their alpha-helix structure was determined by circular dichroism, after which antibacterial tests were then performed to evaluate their antimicrobial activity. Cytotoxicity tests against cancer cells also showed selectivity of pugnin A toward breast cancer (MFC7) cells, and pugnin B toward prostate cancer (PC3) cells. Alternatively, flow cytometry revealed necrotic cell damage with a major cytotoxic effect on human keratinocytes (HaCaT) control cells. Therefore, the pugnins found in the transcriptome of B. pugnax present dual antibacterial–anticancer activity with reduced selectivity to normal eukaryotic cells.
Design and Evaluation of Dissolving Microneedles for Enhanced Dermal Delivery of Propranolol Hydrochloride
Authors: He Jingjing , Zhang Zichen , Zheng Xianzi , Li Lu , Qi Jianping , Wu Wei , Lu Yi
Published: April 2021

Oral propranolol hydrochloride has been the first-line treatment for infantile hemangioma (IH), whereas systemic exposure to propranolol has the potential of causing serious adverse reactions. Dermal delivery of propranolol is preferable due to high local drug concentration and fewer adverse effects. However, propranolol hydrochloride (BCS class I) is highly hydrophilic and has difficulty in penetrating the stratum corneum (SC) barrier. Dissolving microneedles (MNs) are an efficient tool for overcoming the barrier of the SC and enhancing dermal drug delivery. In this study, propranolol hydrochloride-loaded dissolving MNs were fabricated by using hyaluronic acid and polyvinyl pyrrolidone as matrix materials. Controllable drug loading in needle tips was achieved by a two-step casting procedure. The needles were good in mechanical strength for penetrating the SC while presented excellent dissolving capability for releasing propranolol hydrochloride. In comparison with the solution counterpart, irrespective of being applied to intact skin or solid MNs-pretreated skin, dissolving MNs significantly increased the permeability and skin retention of propranolol. In conclusion, dissolving MNs could be a potential approach for enhancing dermal delivery of propranolol to treat IH.
Bacterial Indole-3-Acetic Acid Influences Soil Nitrogen Acquisition in Barley and Chickpea
Authors: Gang Shraddha , Sharma Sheetal , Saraf Meenu , Buck Martin , Schumacher Jorg
Published: April 2021

Farming of barley and chickpea is nitrogen (N) fertilizer dependent. Using strategies that increase the nitrogen use efficiency (NUE) and its components, nitrogen uptake efficiency (NUpE) and nitrogen utilization efficiency (NUtE) would reduce the N fertilizer application in the soil and its adverse environmental effects. We evaluated the effects of three different strains of diazotroph Klebsiella (K.p. SSN1, K.q. SGM81, and K.o. M5a1) to understand the role of biological nitrogen fixation (BNF) and bacterial indole-3-acetic acid (IAA) on NUE of the plants. A field study revealed that K.p. SSN1 results in profound increment of root surface area by eightfold and threefold compared to uninoculated (control) in barley and chickpea, respectively. We measured significant increase in the plant tissue nitrogen, chlorophyll content, protein content, nitrate reductase activity, and nitrate concentration in the inoculated plants (p ≤ 0.05). Treated barley and chickpea exhibited higher NUE and the components compared to the control plants (K.p. SSN1 ≥ K.q. SGM81> K.o. M5a1). Specifically, K.q. SGM81 treatment in barley increased NUpE by 72%, while in chickpea, K.p. SSN1 increased it by 187%. The substantial improvement in the NUpE and NUE by the auxin producers K.p. SSN1 and K.q. SGM81 compared with non-auxin producer K.o. M5a1 was accompanied by an augmented root architecture suggesting larger contribution of IAA over marginal contribution of BNF in nitrogen acquisition from the soil.
A Novel Protein Hydrolysate-Based Biostimulant Improves Tomato Performances under Drought Stress
Authors: Francesca Silvana , Cirillo Valerio , Raimondi Giampaolo , Maggio Albino , Barone Amalia , Rigano Maria Manuela
Published: April 2021

Abiotic stresses adversely affect crop production causing yield reductions in important crops, including tomato (Solanum lycopersicum L.). Among the different abiotic stresses, drought is considered to be the most critical one, since limited water availability negatively impacts plant growth and development, especially in arid and semi-arid areas. The aim of this study was to understand how biostimulants may interact with critical physiological response mechanisms in tomato under limited water availability and to define strategies to improve tomato performances under drought stress. We investigated the physiological responses of the tomato genotype ‘E42’ grown in open fields under optimal conditions (100% irrigation) and limited water availability (50% irrigation) treated or not with a novel protein hydrolysate-based biostimulant (CycoFlow, Agriges, BN, Italy). Plants treated with the protein hydrolysate showed a better water status and pollen viability, which also resulted in higher yield under drought stress compared to untreated plants. The treatment with the biostimulant had also an effect on antioxidant contents and activity in leaves and fruits depending on the level of irrigation provided. Altogether, these results indicate that the application of protein hydrolysates on tomato improved plant performances under limited water availability and in different experimental fields.
Harnessing the Rhizosphere of the Halophyte Grass Aeluropus littoralis for Halophilic Plant-Growth-Promoting Fungi and Evaluation of Their Biostimulant Activities
Authors: Tarroum Mohamed , Ben Romdhane Walid , Ali Ahmed Abdelrahim Mohamed , Al-Qurainy Fahad , Al-Doss Abdullah , Fki Lotfi , Hassairi Afif
Published: April 2021

Hydroponic systems have gained interest and are increasingly used in hot and dry desert areas. Numbers of benefits are offered by hydroponic systems such as the ability to save water, enhance nutrients use efficiency, easy environmental control, and prevention of soil-borne diseases. However, the high consumption of chemical fertilizers for nutrient solution and the sensitivity of closed hydroponic systems to salinity are issues that need solutions. Thus, the main goal of our research activities is to isolate plant growth promoting fungi in order to develop sustainable hydroponic systems. We are working on isolating and testing the possibility to incorporate the cell-free filtrate (CFF) of plant growth promoting fungi (PGPF) in the composition of the nutrient solution. In this work, we isolated six strains of PGPF from the rhizosphere of the halophyte grass Aeluropus littoralis. Phylogenetic analyses of DNA sequences amplified by ITS1 and ITS4 primers identified the isolated fungi as: Byssochlamys spectabilis, Chaetomium globosum, Cephalotheca foveolata, Penicillium melinii, Alternaria tenuissima, and Nigrospora chinensis. The promoting of vigor in tobacco seedlings was used as criteria to evaluate the biostimulant activity of these fungi by adding either their mycelia (DE: direct effect) or their cell-free filtrates (CFF: indirect effect) to the plant-growth media. The best significant growth stimulation was obtained with plants treated by B. spectabilis. However, only the CFFs of Byssochlamys spectabilis (A5.1) and Penicillium melinii (A8) when added at a dilution factor of 1/50 to half-strength nutritive solution (0.5NS) resulted in significant improvement of all assessed growth parameters. Indeed, the A5.1CFF and A8CFF in 0.5NS induced a significant better increase in the biomass production when compared to NS or 0.5NS alone. All fungi produced indole acetic acid in the CFFs, which could be one of the key factors explaining their biostimulant activities. Furthermore, six genes involved in nitrogen-metabolism (NR1 and NRT1), auxin biosynthesis (Tryp1 and YUCCA6-like), and brassinosteroid biosynthesis (DET2 and DWF4) were shown to be induced in roots or leaves following treatment of plants with the all CFFs. This work opens up a prospect to study in deep the biostimulant activity of PGPFs and their applications to decrease the requirement of chemical fertilizers in the hydroponic growing systems.
The Diversity of Volatile Compounds in Australia’s Semi-Desert Genus Eremophila (Scrophulariaceae)
Authors: Sadgrove Nicholas J. , Padilla-González Guillermo F. , Green Alison , Langat Moses K. , Mas-Claret Eduard , Lyddiard Dane , Klepp Julian , Legendre Sarah V. A.-M. , Greatrex Ben W. , Jones Graham L. , Ramli Iskandar M. , Leuner Olga , Fernandez-Cusimamani Eloy
Published: April 2021

Australia’s endemic desert shrubs are commonly aromatic, with chemically diverse terpenes and phenylpropanoids in their headspace profiles. Species from the genus Eremophila (Scrophulariaceae ex. Myoporaceae) are the most common, with 215 recognised taxa and many more that have not yet been described, widely spread across the arid parts of the Australian continent. Over the years, our research team has collected multiple specimens as part of a survey to investigate the chemical diversity of the genus and create leads for further scientific enquiry. In the current study, the diversity of volatile compounds is studied using hydrodistilled essential oils and leaf solvent extracts from 30 taxa. Several rare terpenes and iridoids were detected in chemical profiles widely across the genus, and three previously undescribed sesquiterpenes were isolated and are assigned by 2D NMR—E-11(12)-dehydroisodendrolasin, Z-11-hydroxyisodendrolasin and 10-hydroxydihydro-α-humulene acetate. Multiple sampling from Eremophila longifolia, Eremophila arbuscular, Eremophila latrobei, Eremophila deserti, Eremophila sturtii, Eremophila oppositifolia and Eremophila alternifolia coneys that species in Eremophila are highly chemovariable. However, taxa are generally grouped according to the expression of (1) furanosesquiterpenes, (2) iridoids or oxides, (3) mixtures of 1 and 2, (4) phenylpropanoids, (5) non-furanoid terpenes, (6) mixtures of 4 and 5, and less commonly (7) mixtures of 1 and 5. Furthermore, GC–MS analysis of solvent-extracted leaves taken from cultivated specimens conveys that many heavier ‘volatiles’ with lower vapour pressure are not detected in hydrodistilled essential oils and have therefore been neglected in past chemical studies. Hence, our data reiterate that chemical studies of the genus Eremophila will continue to describe new metabolites and that taxon determination has limited predictive value for the chemical composition.
Myco-Suppression Analysis of Soybean (Glycine max) Damping-Off Caused by Pythium aphanidermatum
Authors: Sayed Shaban R. M. , Abdelmohsen Shaimaa A. M. , Abdelzaher Hani M. A. , Elnaghy Mohammed A. , Mostafa Ashraf A. , Al-Harbi Fatemah F. , Abdelbacki Ashraf M. M.
Published: April 2021

The role of Pythium oligandrum as a biocontrol agent against Pythium aphanidermatum was investigated to avoid the harmful impacts of fungicides. Three isolates of P. oligandrum (MS15, MS19, and MS31) were assessed facing the plant pathogenic P. aphanidermatum the causal agent of Glycine max damping-off. The tested Pythium species were recognized according to their cultural and microscopic characterizations. The identification was confirmed through sequencing of rDNA-ITS regions including the 5.8 S rDNA. The biocontrol agent, P. oligandrum, isolates decreased the mycelial growth of the pathogenic P. aphanidermatum with 71.3%, 67.1%, and 68.7% through mycoparasitism on CMA plates. While the half-strength millipore sterilized filtrates of P. oligandrum isolates degrade the pathogenic mycelial linear growth by 34.1%, 32.5%, and 31.7%, and reduce the mycelial dry weight of the pathogenic P. aphanidermatum by 40.1%, 37.4%, and 36.8%, respectively. Scanning electron microscopy (SEM) of the most effective antagonistic P. oligandrum isolate (MS15) interaction showed coiling, haustorial parts of P. oligandrum to P. aphanidermatum hyphae. Furthermore, P. oligandrum isolates were proven to enhance the germination of Glycine max seedling to 93.3% in damping-off infection using agar pots and promote germination of up to 80% during soil pot assay. On the other hand, P. oligandrum isolates increase the shoot, root lengths, and the number of lateral roots.
COR/LEA Proteins as Indicators of Frost Tolerance in Triticeae: A Comparison of Controlled versus Field Conditions
Authors: Kosová Klára , Klíma Miroslav , Prášil Ilja Tom , Vítámvás Pavel
Published: April 2021

Low temperatures in the autumn induce enhanced expression/relative accumulation of several cold-inducible transcripts/proteins with protective functions from Late-embryogenesis-abundant (LEA) superfamily including dehydrins. Several studies dealing with plants grown under controlled conditions revealed a correlation (significant quantitative relationship) between dehydrin transcript/protein relative accumulation and plant frost tolerance. However, to apply these results in breeding, field experiments are necessary. The aim of the review is to provide a summary of the studies dealing with the relationships between plant acquired frost tolerance and COR/LEA transcripts/proteins relative accumulation in cereals grown in controlled and field conditions. The impacts of cold acclimation and vernalisation processes on the ability of winter-type Triticeae to accumulate COR/LEA proteins are discussed. The factors determining dehydrin relative accumulation under controlled cold acclimation treatments versus field trials during winter seasons are discussed. In conclusion, it can be stated that dehydrins could be used as suitable indicators of winter survival in field-grown winter cereals but only in plant prior to the fulfilment of vernalisation requirement.
Phytostimulatory Influence of Comamonas testosteroni and Silver Nanoparticles on Linum usitatissimum L. under Salinity Stress
Authors: Khalofah Ahlam , Kilany Mona , Migdadi Hussein
Published: April 2021

They were shifting in land use increases salinity stress, significant abiotic stress affecting plant growth, limiting crop productivity. This work aimed to improve Linum usitatissimum L. (linseed) growth under salinity using Comamonas testosteroni and silver nanoparticles (AgNPs). AgNPs were fabricated exploiting Rosmarinus officinalis and monitored by U.V./Vis spectrophotometry scanning electron microscopy (SEM) and Fourier transforms infrared spectroscopy (FTIR). Photosynthetic pigments, enzymatic and nonenzymatic antioxidants of linseed were investigated under salt stress in treated and untreated plants with C. testosteroni alongside AgNPs. Our findings recorded the formation of AgNPs at 457 nm, which were globular and with a diameter of 75 nm. Notably, chlorophyll-a, b, and total chlorophyll reduction while enhanced carotenoids and anthocyanin contents were attained under salinity stress. Total dissoluble sugars, proline, and dissoluble proteins, H2O2, malondialdehyde, enzymatic and nonenzymatic antioxidants were significantly elevated in NaCl well. Combined AgNPs and C. testosteroni elevated photosynthetic pigments. Also, they led to the mounting of soluble sugars, proline, and soluble proteins. H2O2 and malondialdehyde decreased while enzymatic and nonenzymatic antioxidants increased in response to AgNPs, C. testosteroni, and their combination. Thus, AgNPs and C. testosteroni might bio-fertilizers to improve linseed crop productivity under salinity stress.
Effects of Monochromatic Illumination with LEDs Lights on the Growth and Photosynthetic Performance of Auxenochlorella protothecoides in Photo- and Mixotrophic Conditions
Authors: Markou Giorgos , Diamantis Alexandros , Korozi Evagelina , Tsagou Vasiliki , Kefalogianni Io , Chatzipavlidis Iordanis
Published: April 2021

This study examined the effects of monochromatic illumination (blue, red, green and yellow) employing light-emitting diodes (LEDs), trophic conditions (photoautotrophic and mixotrophic), and nitrogen availability (high and low peptone concentration) on the growth and biochemical composition of Auxenochlorella protothecoides. The results revealed that mixotrophic conditions did not favor A. protothecoides, giving lower growth rates compared to heterotrophy (dark conditions). However, mixotrophy gave significantly higher growth rates compared to photoautotrophy. The best light wavelengths for mixotrophic cultivation were that of white and red. In all cases investigated in this study, high peptone concentration (4 g/L) resulted in decreased growth rates. Regarding the biochemical composition of A. protothecoides, the strongest effect, irrespective of trophic conditions, was caused by nitrogen availability (peptone concentration). Specifically, at nitrogen replete conditions (4 g/L peptone), biomass was rich in proteins (32–67%), whereas under deplete conditions (0.5 g/L peptone), A. protothecoides accumulated mainly carbohydrates (up to 56%). Mixotrophic conditions generally favored higher carbohydrate content, whereas photoautotrophic conditions favored higher protein content. The different illumination spectra did not have any clear effect on the biochemical composition (metabolites content), except that, in all trophic conditions, the use of the green spectrum resulted in higher chlorophyll b content. Chlorophyll a fluorescence studies revealed that the trophic conditions and the high peptone concentrations impacted the photosystem II (PSII) performance, and also affected plastoquinone re-oxidation kinetics and the heterogeneity of the PSII reaction centers.
Intraspecific Variation in Nickel Tolerance and Hyperaccumulation among Serpentine and Limestone Populations of Odontarrhena serpyllifolia (Brassicaceae: Alysseae) from the Iberian Peninsula
Authors: Pollard A. Joseph , McCartha Grace L. , Quintela-Sabarís Celestino , Flynn Thomas A. , Sobczyk Maria K. , Smith J. Andrew C.
Published: April 2021

Odontarrhena serpyllifolia (Desf.) Jord. & Fourr. (=Alyssum serpyllifolium Desf.) occurs in the Iberian Peninsula and adjacent areas on a variety of soils including both limestone and serpentine (ultramafic) substrates. Populations endemic to serpentine are known to hyperaccumulate nickel, and on account of this remarkable phenotype have, at times, been proposed for recognition as taxonomically distinct subspecies or even species. It remains unclear, however, to what extent variation in nickel hyperaccumulation within this taxon merely reflects differences in the substrate, or whether the different populations show local adaptation to their particular habitats. To help clarify the physiological basis of variation in nickel hyperaccumulation among these populations, 3 serpentine accessions and 3 limestone accessions were cultivated hydroponically under common-garden conditions incorporating a range of Ni concentrations, along with 2 closely related non-accumulator species, Clypeola jonthlaspi L. and Alyssum montanum L. As a group, serpentine accessions of O. serpyllifolia were able to tolerate Ni concentrations approximately 10-fold higher than limestone accessions, but a continuous spectrum of Ni tolerance was observed among populations, with the least tolerant serpentine accession not being significantly different from the most tolerant limestone accession. Serpentine accessions maintained relatively constant tissue concentrations of Ca, Mg, K, and Fe across the whole range of Ni exposures, whereas in the limestone accessions, these elements fluctuated widely in response to Ni toxicity. Hyperaccumulation of Ni, defined here as foliar Ni concentrations exceeding 1g kg−1 of dry biomass in plants not showing significant growth reduction, occurred in all accessions of O. serpyllifolia, but the higher Ni tolerance of serpentine accessions allowed them to hyperaccumulate more strongly. Of the reference species, C. jonthlaspi responded similarly to the limestone accessions of O. serpyllifolia, whereas A. montanum displayed by far the lowest degree of Ni tolerance and exhibited low foliar Ni concentrations, which only exceeded 1 g kg−1 in plants showing severe Ni toxicity. The continuous spectrum of physiological responses among these accessions does not lend support to segregation of the serpentine populations of O. serpyllifolia as distinct species. However, the pronounced differences in degrees of Ni tolerance, hyperaccumulation, and elemental homeostasis observed among these accessions under common-garden conditions argues for the existence of population-level adaptation to their local substrates.
Production of Phytotoxic Metabolites by Botryosphaeriaceae in Naturally Infected and Artificially Inoculated Grapevines
Authors: Reveglia Pierluigi , Billones-Baaijens Regina , Millera Niem Jennifer , Masi Marco , Cimmino Alessio , Evidente Antonio , Savocchia Sandra
Published: April 2021

Grapevine trunk diseases (GTDs) are considered a serious problem to viticulture worldwide. Several GTD fungal pathogens produce phytotoxic metabolites (PMs) that were hypothesized to migrate to the foliage where they cause distinct symptoms. The role of PMs in the expression of Botryosphaeria dieback (BD) symptoms in naturally infected and artificially inoculated wood using molecular and analytical chemistry techniques was investigated. Wood samples from field vines naturally infected with BD and one-year-old vines inoculated with Diplodia seriata, Spencermartinsia viticola and Dothiorella vidmadera were analysed by cultural isolations, quantitative PCR (qPCR) and targeted LC-MS/MS to detect three PMs: (R)-mellein, protocatechuic acid and spencertoxin. (R)-mellein was detected in symptomatic naturally infected wood and vines artificially inoculated with D. seriata but was absent in all non-symptomatic wood. The amount of (R)-mellein detected was correlated with the amount of pathogen DNA detected by qPCR. Protocatechuic acid and spencertoxin were absent in all inoculated wood samples. (R)-mellein may be produced by the pathogen during infection to break down the wood, however it was not translocated into other parts of the vine. The foliar symptoms previously reported in vineyards may be due to a combination of PMs produced and climatic and physiological factors that require further investigation.
High Throughput Centrifugal Electrospinning of Polyacrylonitrile Nanofibers for Carbon Fiber Nonwovens
Authors: Hoffmann Andreas , Kuehne Alexander J. C.
Published: April 2021

Carbon nanofiber nonwovens are promising materials for electrode or filtration applications; however, their utilization is obviated by a lack of high throughput production methods. In this study, we utilize a highly effective high-throughput method for the fabrication of polyacrylonitrile (PAN) nanofibers as a nonwoven on a dedicated substrate. The method employs rotational-, air pressure- and electrostatic forces to produce fibers from the inner edge of a rotating bell towards a flat collector. We investigate the impact of all above-mentioned forces on the fiber diameter, morphology, and bundling of the carbon-precursor PAN fibers. The interplay of radial forces with collector-facing forces has an influence on the uniformity of fiber deposition. Finally, the obtained PAN nanofibers are converted to carbon nonwovens by thermal treatment.