bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing the Trypanosomatidic GSK Kinetobox for the Inhibition of Parasitic Pteridine and Dihydrofolate Reductases
Authors: Santucci Matteo , Luciani Rosaria , Gianquinto Eleonora , Pozzi Cecilia , Pisa Flavio di , dello Iacono Lucia , Landi Giacomo , Tagliazucchi Lorenzo , Mangani Stefano , Spyrakis Francesca , Costi Maria Paola
Published: December 2021

Three open-source anti-kinetoplastid chemical boxes derived from a whole-cell phenotypic screening by GlaxoSmithKline (Tres Cantos Anti-Kinetoplastid Screening, TCAKS) were exploited for the discovery of a novel core structure inspiring new treatments of parasitic diseases targeting the trypansosmatidic pteridine reductase 1 (PTR1) and dihydrofolate reductase (DHFR) enzymes. In total, 592 compounds were tested through medium-throughput screening assays. A subset of 14 compounds successfully inhibited the enzyme activity in the low micromolar range of at least one of the enzymes from both Trypanosoma brucei and Lesihmania major parasites (pan-inhibitors), or from both PTR1 and DHFR-TS of the same parasite (dual inhibitors). Molecular docking studies of the protein–ligand interaction focused on new scaffolds not reproducing the well-known antifolate core clearly explaining the experimental data. TCMDC-143249, classified as a benzenesulfonamide derivative by the QikProp descriptor tool, showed selective inhibition of PTR1 and growth inhibition of the kinetoplastid parasites in the 5 μM range. In our work, we enlarged the biological profile of the GSK Kinetobox and identified new core structures inhibiting selectively PTR1, effective against the kinetoplastid infectious protozoans. In perspective, we foresee the development of selective PTR1 and DHFR inhibitors for studies of drug combinations.
Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
Authors: Ural Merve Seray , Menéndez-Miranda Mario , Salzano Giuseppina , Mathurin Jérémie , Aybeke Ece Neslihan , Deniset-Besseau Ariane , Dazzi Alexandre , Porcino Marianna , Martineau-Corcos Charlotte , Gref Ruxandra
Published: December 2021

Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented by engineering pH-responsive nanoparticles (NPs) capable to incorporate high VCM payload and deliver it specifically at slightly acidic pH corresponding to infection sites. Taking advantage of peculiar physicochemical properties of VCM, here we show how to incorporate VCM efficiently in biodegradable NPs made of poly(lactic-co-glycolic acid) and polylactic acid (co)polymers. The NPs were prepared by a simple and reproducible method, establishing strong electrostatic interactions between VCM and the (co)polymers’ end groups. VCM payloads reached up to 25 wt%. The drug loading mechanism was investigated by solid state nuclear magnetic resonance spectroscopy. The engineered NPs were characterized by a set of advanced physicochemical methods, which allowed examining their morphology, internal structures, and chemical composition on an individual NP basis. The compartmentalized structure of NPs was evidenced by cryogenic transmission electronic microscopy, whereas the chemical composition of the NPs’ top layers and core was obtained by electron microscopies associated with energy-dispersive X-ray spectroscopy. Noteworthy, atomic force microscopy coupled to infrared spectroscopy allowed mapping the drug location and gave semiquantitative information about the loadings of individual NPs. In addition, the NPs were stable upon storage and did not release the incorporated drug at neutral pH. Interestingly, a slight acidification of the medium induced a rapid VCM release. The compartmentalized NPs could find potential applications for controlled VCM release at an infected site with local acidic pH.
Nanoformulations of α-Mangostin for Cancer Drug Delivery System
Authors: Meylina Lisna , Muchtaridi Muchtaridi , Joni I Made , Mohammed Ahmed Fouad Abdelwahab , Wathoni Nasrul
Published: December 2021

Natural compounds are emerging as effective agents for the treatment of malignant diseases. The active constituent of α-mangostin from the pericarp of Garcinia mangostana L. has earned significant interest as a plant base compound with anticancer properties. Despite α-mangostin’s superior properties as an anticancer agent, its applications are limited due to its poor solubility and physicochemical stability, rapid systemic clearance, and low cellular uptake. Our review aimed to summarize and discuss the nanoparticle formulations of α-mangostin for cancer drug delivery systems from published papers recorded in Scopus, PubMed, and Google Scholar. We investigated various types of α-mangostin nanoformulations to improve its anticancer efficacy by improving bioavailability, cellular uptake, and localization to specific areas These nanoformulations include nanofibers, lipid carrier nanostructures, solid lipid nanoparticles, polymeric nanoparticles, nanomicelles, liposomes, and gold nanoparticles. Notably, polymeric nanoparticles and nanomicelles can increase the accumulation of α-mangostin into tumors and inhibit tumor growth in vivo. In addition, polymeric nanoparticles with the addition of target ligands can increase the cellular uptake of α-mangostin. In conclusion, nanoformulations of α-mangostin are a promising tool to enhance the cellular uptake, accumulation in cancer cells, and the efficacy of α-mangostin as a candidate for anticancer drugs.
Smart Device for Biologically Enhanced Functional Regeneration of Osteo–Tendon Interface
Authors: Faccendini Angela , Bianchi Eleonora , Ruggeri Marco , Vigani Barbara , Perotti Cesare , Pavesi Francesco Claudio , Caliogna Laura , Natali Francesca , Del Favero Elena , Cantu’ Laura , Ferrari Franca , Rossi Silvia , Sandri Giuseppina
Published: December 2021

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively—important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration.
PL1 Peptide Engages Acidic Surfaces on Tumor-Associated Fibronectin and Tenascin Isoforms to Trigger Cellular Uptake
Authors: Lingasamy Prakash , Põšnograjeva Kristina , Kopanchuk Sergei , Tobi Allan , Rinken Ago , General Ignacio J. , Asciutto Eliana K. , Teesalu Tambet
Published: December 2021

Tumor extracellular matrix (ECM) is a high-capacity target for the precision delivery of affinity ligand-guided drugs and imaging agents. Recently, we developed a PL1 peptide (sequence: PPRRGLIKLKTS) for systemic targeting of malignant ECM. Here, we map the dynamics of PL1 binding to its receptors Fibronectin Extra Domain B (FN-EDB) and Tenascin C C-isoform (TNC-C) by computational modeling and cell-free binding studies on mutated receptor proteins, and study cellular binding and internalization of PL1 nanoparticles in cultured cells. Molecular dynamics simulation and docking analysis suggested that the engagement of PL1 peptide with both receptors is primarily driven by electrostatic interactions. Substituting acidic amino acid residues with neutral amino acids at predicted PL1 binding sites in FN-EDB (D52N-D49N-D12N) and TNC-C (D39N-D45N) resulted in the loss of binding of PL1 nanoparticles. Remarkably, PL1-functionalized nanoparticles (NPs) were not only deposited on the target ECM but bound the cells and initiated a robust cellular uptake via a pathway resembling macropinocytosis. Our studies establish the mode of engagement of the PL1 peptide with its receptors and suggest applications for intracellular delivery of nanoscale payloads. The outcomes of this work can be used for the development of PL1-derived peptides with improved stability, affinity, and specificity for precision targeting of the tumor ECM and malignant cells.
In Vitro and In Vivo Inhibition of MATE1 by Tyrosine Kinase Inhibitors
Authors: Uddin Muhammad Erfan , Talebi Zahra , Chen Sijie , Jin Yan , Gibson Alice A. , Noonan Anne M. , Cheng Xiaolin , Hu Shuiying , Sparreboom Alex
Published: December 2021

The membrane transport of many cationic prescription drugs depends on facilitated transport by organic cation transporters of which several members, including OCT2 (SLC22A2), are sensitive to inhibition by select tyrosine kinase inhibitors (TKIs). We hypothesized that TKIs may differentially interact with the renal transporter MATE1 (SLC47A1) and influence the elimination and toxicity of the MATE1 substrate oxaliplatin. Interactions with FDA-approved TKIs were evaluated in transfected HEK293 cells, and in vivo pharmacokinetic studies were performed in wild-type, MATE1-deficient, and OCT2/MATE1-deficient mice. Of 57 TKIs evaluated, 37 potently inhibited MATE1 function by >80% through a non-competitive, reversible, substrate-independent mechanism. The urinary excretion of oxaliplatin was reduced by about 2-fold in mice with a deficiency of MATE1 or both OCT2 and MATE1 (p < 0.05), without impacting markers of acute renal injury. In addition, genetic or pharmacological inhibition of MATE1 did not significantly alter plasma levels of oxaliplatin, suggesting that MATE1 inhibitors are unlikely to influence the safety or drug-drug interaction liability of oxaliplatin-based chemotherapy.
Synergistic Effect of Acetazolamide-(2-hydroxy)propyl β-Cyclodextrin in Timolol Liposomes for Decreasing and Prolonging Intraocular Pressure Levels
Authors: Arroyo-García Carmen M. , Quinteros Daniela , Palma Santiago D. , Jiménez de los Santos Cesáreo J. , Moyano José R. , Rabasco Antonio M. , González-Rodríguez María Luisa
Published: December 2021

The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz despite the weak binding ability of the complex. Ch disturbed the stability and solubility parameters of Acz due to the fact of its competence by CD; thus, Chems (steroid derivative) was selected for further liposome formulation studies. The optimization of the lipid bilayer composition (DDAB, 0.0173 mmol and no double loading) and the extrusion as methods to reduce vesicle size were crucial for improving the physico-chemical properties and encapsulation efficiency of both drugs. In vitro release and permeation studies demonstrated that the CLL formulation showed improvement in in vitro drug release and permeation compared to the liposomal formulations with a single drug (TM-L and AczHP-L) and the standard solutions (TM-S and AczHP-S). CLL showed high efficacy in reducing and prolonging IOP, suggesting that the synergistic effect of TM and Acz on aqueous humor retention and the presence of this cyclodextrin and liposomes as permeation enhancers are responsible for the success of this strategy of co-loading for glaucoma therapy.
Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis
Authors: Camargo Guilherme dos Anjos , Ferreira Leandro , Schebelski Diego José , Lyra Amanda Martinez , Barboza Fernanda Malaquias , Carletto Bruna , Koga Adriana Yuriko , Semianko Betina Christi , Dias Daniele Toniolo , Lipinski Leandro Cavalcante , Novatski Andressa , Raman Vijayasankar , Manfron Jane , Nadal Jessica Mendes , Farago Paulo Vitor
Published: December 2021

Background: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. Methods: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. Results: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (−38 to −42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer–Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. Conclusions: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.
Antisense Oligonucleotide-Based Therapy of Viral Infections
Authors: Tarn Woan-Yuh , Cheng Yun , Ko Shih-Han , Huang Li-Min
Published: December 2021

Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.
Optimizing Solvent Selection and Processing Conditions to Generate High Bulk-Density, Co-Precipitated Amorphous Dispersions of Posaconazole
Authors: Frank Derek , Schenck Luke , Koynov Athanas , Su Yongchao , Li Yongjun , Variankaval Narayan
Published: December 2021

Co-precipitation is an emerging method to generate amorphous solid dispersions (ASDs), notable for its ability to enable the production of ASDs containing pharmaceuticals with thermal instability and limited solubility. As is true for spray drying and other unit operations to generate amorphous materials, changes in processing conditions during co-precipitation, such as solvent selection, can have a significant impact on the molecular and bulk powder properties of co-precipitated amorphous dispersions (cPAD). Using posaconazole as a model API, this work investigates how solvent selection can be leveraged to mitigate crystallization and maximize bulk density for precipitated amorphous dispersions. A precipitation process is developed to generate high-bulk-density amorphous dispersions. Insights from this system provide a mechanistic rationale to control the solid-state and bulk powder properties of amorphous dispersions.
Keratin Biomaterials in Skin Wound Healing, an Old Player in Modern Medicine: A Mini Review
Authors: Konop Marek , Rybka Mateusz , Drapała Adrian
Published: December 2021

Impaired wound healing is a major medical problem. To solve it, researchers around the world have turned their attention to the use of tissue-engineered products to aid in skin regeneration in case of acute and chronic wounds. One of the primary goals of tissue engineering and regenerative medicine is to develop a matrix or scaffold system that mimics the structure and function of native tissue. Keratin biomaterials derived from wool, hair, and bristle have been the subjects of active research in the context of tissue regeneration for over a decade. Keratin derivatives, which can be either soluble or insoluble, are utilized as wound dressings since keratins are dynamically up-regulated and needed in skin wound healing. Tissue biocompatibility, biodegradability, mechanical durability, and natural abundance are only a few of the keratin biomaterials’ properties, making them excellent wound dressing materials to treat acute and chronic wounds. Several experimental and pre-clinical studies described the beneficial effects of the keratin-based wound dressing in faster wound healing. This review focuses exclusively on the biomedical application of a different type of keratin biomaterials as a wound dressing in pre-clinical and clinical conditions.
MSC Secretome as a Promising Tool for Neuroprotection and Neuroregeneration in a Model of Intracerebral Hemorrhage
Authors: Karagyaur Maxim , Dzhauari Stalik , Basalova Nataliya , Aleksandrushkina Natalia , Sagaradze Georgy , Danilova Natalia , Malkov Pavel , Popov Vladimir , Skryabina Mariya , Efimenko Anastasia , Tkachuk Vsevolod
Published: December 2021

Multipotent mesenchymal stromal cells (MSCs) are considered to be critical contributors to injured tissue repair and regeneration, and MSC-based therapeutic approaches have been applied to many peripheral and central neurologic disorders. It has been demonstrated that the beneficial effects of MSC are mainly mediated by the components of their secretome. In the current study, we have explored the neuroprotective potential of the MSC secretome in a rat model of intracerebral hemorrhage and shown that a 10-fold concentrated secretome of human MSC and its combination with the brain-derived neurotrophic factor (BDNF) provided a better survival and neurological outcome of rats within 14 days of intracerebral hemorrhage compared to the negative (non-treated) and positive (BDNF) control groups. We found that it was due to the ability of MSC secretome to stimulate neuron survival under conditions of glutamate-induced neurotoxicity. However, the lesion volume did not shrink in these rats, and this also correlated with prominent microglia activation. We hypothesize that this could be caused by the species-specificity of the used MSC secretome and provide evidence to confirm this. Thus, we have found that allogenic rat MSC secretome was more effective than xenogenic human MSC secretome in the rat intracerebral hemorrhage model: it reduced the volume of the lesion and promoted excellent survival and neurological outcome of the treated rats.
Investigating Structural Property Relationships to Enable Repurposing of Pharmaceuticals as Zinc Ionophores
Authors: Kavanagh Oisín , Elmes Robert , O’Sullivan Finbarr , Farragher John , Robinson Shane , Walker Gavin
Published: December 2021

The importance of zinc in biology has gained greater recognition in recent years due to its essential contributions to the function of many endogenous enzymes. Disruption of zinc homeostasis may be useful in treating pathological conditions, such as Alzheimer’s, and for antiviral purposes. Despite the growth of knowledge and increased interest in zinc, little is known about the structure and function of zinc ionophores. In this study we analyse the Cambridge Structural Database and solution complexation studies found in the literature to identify key functional groups which may confer zinc ionophorism. Pharmaceuticals, nutraceuticals and amino acids with these functionalities were selected to enable us to explore the translatability of ionophoric activity from in vitro assays to cellular systems. We find that although certain species may complex to zinc in the solid and solution states, and may carry ions across simple membrane systems, this does not necessarily translate into ionophoric activity. We propose that the CSD can help refine key functionalities but that ionophoric activity must be confirmed in cellular systems.
Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy
Authors: Shao Zitong , Tai Waiting , Qiu Yingshan , Man Rico C. H. , Liao Qiuying , Chow Michael Y. T. , Kwok Philip C. L. , Lam Jenny K. W.
Published: December 2021

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.
Stimuli-Responsive Polymers for Transdermal, Transmucosal and Ocular Drug Delivery
Authors: Berillo Dmitriy , Zharkinbekov Zharylkasyn , Kim Yevgeniy , Raziyeva Kamila , Temirkhanova Kamila , Saparov Arman
Published: December 2021

Despite their conventional and widespread use, oral and intravenous routes of drug administration face several limitations. In particular, orally administered drugs undergo enzymatic degradation in the gastrointestinal tract and first-pass metabolism in the liver, which tend to decrease their bioavailability. Intravenous infusions of medications are invasive, painful and stressful for patients and carry the risk of infections, tissue damage and other adverse reactions. In order to account for these disadvantages, alternative routes of drug delivery, such as transdermal, nasal, oromucosal, ocular and others, have been considered. Moreover, drug formulations have been modified in order to improve their storage stability, solubility, absorption and safety. Recently, stimuli-responsive polymers have been shown to achieve controlled release and enhance the bioavailability of multiple drugs. In this review, we discuss the most up-to-date use of stimuli-responsive materials in order to optimize the delivery of medications that are unstable to pH or undergo primary metabolism via transdermal, nasal, oromucosal and ocular routes. Release kinetics, diffusion parameters and permeation rate of the drug via the mucosa or skin are discussed as well.
First Demonstration of Calibrated Color Imaging by the CAOS Camera
Authors: Riza Nabeel A. , Ashraf Nazim
Published: December 2021

The Coded Access Optical Sensor (CAOS) camera is a novel, single unit, full spectrum (UV to short-wave IR bands), linear, high dynamic range (HDR) camera. In this paper, calibrated color target imaging using the CAOS camera and a comparison to a commercial HDR CMOS camera is demonstrated for the first time. The first experiment using a calibrated color check chart indicates that although the CMOS sensor-based camera has an 87 dB manufacturer-specified HDR range, unrestricted usage of this CMOS camera’s output range greatly fails quality color recovery. On the other hand, the intrinsically linear full dynamic range operation CAOS camera color image recovery generally matches the restricted linear-mode commercial CMOS sensor-based camera recovery for the presented 39.5 dB non-HDR target that also matches the near 40 dB linear camera response function (CRF) range of the CMOS camera. Specifically, compared to the color checker chart manufacturer provided XYZ values for the calibrated target, percentage XYZ mean errors of 8.3% and 10.9% are achieved for the restricted linear range CMOS camera and CAOS camera, respectively. An alternate color camera assessment gives CIE ΔE00 mean values of 4.59 and 5.7 for the restricted linear range CMOS camera and CAOS camera, respectively. Unlike the CMOS camera lens optics and its photo-detection electronics, no special linear response optics and photo-detector designs were used for the experimental CAOS camera, nevertheless, a good and equivalent color recovery was achieved. Given the limited HDR linear range capabilities of a CMOS camera and the intrinsically wide linear HDR capability of a CAOS camera, a combined CAOS-CMOS mode of the CAOS smart camera is prudent and can empower HDR color imaging. Applications for such a hybrid camera includes still photography imaging, especially for quantitative imaging of biological samples, valuable artworks and archaeological artefacts that require authentic color data generation for reliable medical decisions as well as forgery preventing verifications.
Interstitial Telomeric-like Repeats (ITR) in Seed Plants as Assessed by Molecular Cytogenetic Techniques: A Review
Authors: Maravilla Alexis J. , Rosato Marcela , Rosselló Josep A.
Published: December 2021

The discovery of telomeric repeats in interstitial regions of plant chromosomes (ITRs) through molecular cytogenetic techniques was achieved several decades ago. However, the information is scattered and has not been critically evaluated from an evolutionary perspective. Based on the analysis of currently available data, it is shown that ITRs are widespread in major evolutionary lineages sampled. However, their presence has been detected in only 45.6% of the analysed families, 26.7% of the sampled genera, and in 23.8% of the studied species. The number of ITR sites greatly varies among congeneric species and higher taxonomic units, and range from one to 72 signals. ITR signals mostly occurs as homozygous loci in most species, however, odd numbers of ITR sites reflecting a hemizygous state have been reported in both gymnosperm and angiosperm groups. Overall, the presence of ITRs appears to be poor predictors of phylogenetic and taxonomic relatedness at most hierarchical levels. The presence of ITRs and the number of sites are not significantly associated to the number of chromosomes. The longitudinal distribution of ITR sites along the chromosome arms indicates that more than half of the ITR presences are between proximal and terminal locations (49.5%), followed by proximal (29.0%) and centromeric (21.5%) arm regions. Intraspecific variation concerning ITR site number, chromosomal locations, and the differential presence on homologous chromosome pairs has been reported in unrelated groups, even at the population level. This hypervariability and dynamism may have likely been overlooked in many lineages due to the very low sample sizes often used in cytogenetic studies.
Pre-Sowing Treatments Improve Germinability of South Texas Native Plant Seeds
Authors: Lavallee Kaitlynn , Soti Pushpa Gautam , Rodrigo Hansapani , Kariyat Rupesh , Racelis Alexis
Published: December 2021

The incorporation of native plant species is central to restoration efforts, but this is often limited by both the availability of seeds and the relatively low viability and germination rates of commercially available seeds. Although pre-sowing treatments are commonly used to improve germination rates of seeds, the efficacy of these treatments is found to vary across species. In this study, we tested how four pre-sow treatments (physical scarification, acid scarification, cold stratification, and aerated hydropriming) affected the viability and seed germination rates of 12 commercially available plant species native to south Texas and commonly used in restoration efforts. Our results show that the viability of the seeds have a wide range, from 78% to 1.25%. Similarly, the total germination rate ranged from 62% to 0%. We found that pre-sowing treatments accelerated the germination rate in 9 of 12 plant species tested, but the effect varied by treatment. Collectively, our results identify various methods to achieve the best germination rates for native plants of south Texas, to help improve restoration efforts across the region.
Characterization of Maize Hybrids (Zea mays L.) for Detecting Salt Tolerance Based on Morpho-Physiological Characteristics, Ion Accumulation and Genetic Variability at Early Vegetative Stage
Authors: Huqe Md Al Samsul , Haque Md Sabibul , Sagar Ashaduzzaman , Uddin Md Nesar , Hossain Md Alamgir , Hossain AKM Zakir , Rahman Md Mustafizur , Wang Xiukang , Al-Ashkar Ibrahim , Ueda Akihiro , EL Sabagh Ayman
Published: December 2021

Increasing soil salinity due to global warming severely restricts crop growth and yield. To select and recommend salt-tolerant cultivars, extensive genotypic screening and examination of plants’ morpho-physiological responses to salt stress are required. In this study, 18 prescreened maize hybrid cultivars were examined at the early growth stage under a hydroponic system using multivariate analysis to demonstrate the genotypic and phenotypic variations of the selected cultivars under salt stress. The seedlings of all maize cultivars were evaluated with two salt levels: control (without NaCl) and salt stress (12 dS m−1 simulated with NaCl) for 28 d. A total of 18 morpho-physiological and ion accumulation traits were dissected using multivariate analysis, and salt tolerance index (STI) values of the examined traits were evaluated for grouping of cultivars into salt-tolerant and -sensitive groups. Salt stress significantly declined all measured traits except root–shoot ratio (RSR), while the cultivars responded differently. The cultivars were grouped into three clusters and the cultivars in Cluster-1 such as Prabhat, UniGreen NK41, Bisco 51, UniGreen UB100, Bharati 981 and Star Beej 7Star exhibited salt tolerance to a greater extent, accounting for higher STI in comparison to other cultivars grouped in Cluster-2 and Cluster-3. The high heritability (h2bs, >60%) and genetic advance (GAM, >20%) were recorded in 13 measured traits, indicating considerable genetic variations present in these traits. Therefore, using multivariate analysis based on the measured traits, six hybrid maize cultivars were selected as salt-tolerant and some traits such as Total Fresh Weight (TFW), Total Dry Weight (TDW), Total Na+, Total K+ contents and K+–Na+ Ratio could be effectively used for the selection criteria evaluating salt-tolerant maize genotypes at the early seedling stage.
Use of Natural Products on the Control of Aspergillus flavus and Production of Aflatoxins In Vitro and on Tomato Fruit
Authors: Segura-Palacios Mario Alberto , Correa-Pacheco Zormy Nacary , Corona-Rangel Maria Luisa , Martinez-Ramirez Ollin Celeste , Salazar-Piña Dolores Azucena , Ramos-García Margarita de Lorena , Bautista-Baños Silvia
Published: December 2021

Aspergillus flavus affects fresh and dry fruit and vegetable products, and its toxic metabolites, namely aflatoxins, cause serious damage in humans. The objective of this research study was to evaluate the effect of commercial natural products as well as edible and nanostructured chitosan coatings on the development of A. flavus and on the production of aflatoxins in vitro and in tomato. Treatments were as follows: chitosan 1%, chitosan coating, chitosan nanostructured coating, Citrocover 1% (citrus seed extract), Resinadher 0.5% (pine resin extract), mancozeb 2%, and water. The variables were as follows: halo inhibition, spore production, and aflatoxins content. In fruit, the following were evaluated: disease incidence, mycelial growth, and aflatoxin production. An ANOVA (Tukey: p < 0.05) was used. In vitro results showed that Citrocover and Resinadher reduced sporulation (0.2 and 0.9 × 105 spores mL−1, respectively), while chitosan inhibited the production of aflatoxins. With Resinadher and Citrocover, tomato fruit had the lowest incidence, mycelial growth, and aflatoxin production with corresponding values of 0%, 0.0 cm2, and 0.95 ppb, respectively, and 7%, 0.2 cm2, and 1.77 ppb, respectively. The use of Citrocover and Resinadher could be a viable alternative to decrease the development of A. flavus in tomato fruit.
Effect of ZnO Nanoparticles on Growth and Biochemical Responses of Wheat and Maize
Authors: Srivastav Akansha , Ganjewala Deepak , Singhal Rakesh Kumar , Rajput Vishnu D. , Minkina Tatiana , Voloshina Marina , Srivastava Sudhakar , Shrivastava Manoj
Published: December 2021

Zinc is an essential element that is also renowned for widespread contamination and toxicity at high concentrations. The present study was carried out to analyze the responses induced by lower, as well as higher, doses of zinc (0–200 mg/L), in the form of zinc oxide nanoparticles (ZnO NPs) in wheat and maize, for a period of 21 days. Accumulation of zinc increases with increasing Zn doses in both wheat and maize, with higher doses being in wheat (121 mg/kg in root and 66 mg/kg in shoot) than in maize (95 mg/kg in root and 48 mg/kg in shoot). The activity of alpha-amylase showed increase, while that of dehydrogenase decline, in response to ZnO NPs. The length and biomass of plants and photosynthetic pigments increased slightly upon ZnO NPs supply. Malondialdehyde content showed a progressive increase in root and shoot of both plants. However, in response, antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase, and catalase) showed increase up to lower concentrations (100 mg/L) of ZnO NPs but decline variably at higher levels (150–200 mg/L) in wheat and maize. The results suggest that lower supply of ZnO NPs (100 mg/L) could be stimulatory to the growth of plants and can be recommended as a Zn fertilizer source for crop production.
Purshia plicata Triggers and Regulates Proteins Related to Apoptosis in HeLa Cancer Cells
Authors: Álvarez-Ortiz Patricia , Ascacio-Valdés Juan , Vera-Reyes Ileana , Esparza-González Cecilia , Rodríguez-Herrera Raúl , Salinas-Santander Mauricio , del Ángel-Martínez Mayela , Morlett-Chávez Antonio
Published: December 2021

Cervical cancer represents a public health problem, develops resistance to traditional therapies and cost-of-treatment is high. These disadvantages have led to the search for alternative bioactive-compound-based therapies. Said bioactive compounds include phenolic compounds, flavonoids, and tannins. The present study aimed to evaluate the therapeutic effect of a P. plicata extract on the HeLa cell line. Viability and apoptosis assays were run on the two cell lines treated with the extract. The peptides, up- and down-expressed in both cell lines, were identified by PDQuest analysis software and high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Our results show that a 500 mg/L treatment deregulated cell viability, with different apoptotic morphologies observed which are associated with the presence of bio-compounds, which up- and down-regulated the peptides. In conclusion, P. plicata regulates proteins associated with apoptosis in HeLa cancer cells.
Multi-Criteria Analysis for the Prioritization of Areas for the In Situ Conservation of Crataegus L., an Underutilized Fruit Tree in Mexico
Authors: Vera-Sánchez Karina Sandibel , Parra-Quijano Mauricio , Nieto-Ángel Raúl , Barrientos-Priego Alejandro F.
Published: December 2021

Complementary ex situ and in situ conservation, including the on-farm alternative, is a highly desired and dynamic strategy that allows the natural evolution of the conserved germplasm. Due to the high costs involved, in addition to the limitations of both economic and human resources, in situ conservation must focus on areas where the greatest benefits are obtained, and the efforts made result in better impacts. Therefore, using spatial multi-criteria analysis and expert knowledge, 22 and 23 criteria were obtained as important for the conservation of wild and cultivated hawthorn, respectively. Criteria weights were calculated by the analytic hierarchy process and expert knowledge. The results showed species richness, phenotypic and ecogeographic diversity, and areas not covered by the official protected areas network were the most important criteria for in situ conservation of wild hawthorn. Prioritized areas were particularly focused in Chiapas, State of Mexico and Morelos. The prioritized areas for the in situ conservation of cultivated hawthorn were mostly defined by criteria such as number of cultivated varieties, number of uses, phenotypic diversity, ecogeographical diversity, and areas with rainfed agriculture. These areas were located mainly in Puebla. From this study, we propose a list of priority areas for the in situ conservation of both cultivated and wild hawthorn.
Antifungal Activity against Fusarium oxysporum of Botanical End-Products: An Integration of Chemical Composition and Antifungal Activity Datasets to Identify Antifungal Bioactives
Authors: Cárdenas-Laverde Diego , Barbosa-Cornelio Ricardo , Coy-Barrera Ericsson
Published: December 2021

Plants produce various compounds as defensive barriers to naturally control fungal diseases. Among them, vascular wilt caused by Fusarium oxysporum is one of the most destructive diseases in crops, causing relevant economic losses. The application of synthetic fungicides is the most used management for this disease. However, this kind of method also involves adverse environmental impacts. Therefore, alternative methods are continuously being developed as a strategy to be involved in integrated pest management programs. Thus, as part of our research on antifungals of plant origin, a group of botanical extracts was assessed for the respective inhibitory effect on mycelium and conidia of F. oxysporum. Mycelial growth inhibition was measured in 12-well plates containing amended semi-solid medium, whereas conidial susceptibility was determined through microdilution. The identification of the bioactive compounds among test extracts was performed using an indirect approach, consisting of the integration of chemical composition and antifungal activity datasets through single-Y orthogonal partial least squares (OPLS) regression. Results showed that Piper aduncum extract was the most potent mycelial growth inhibitor whereas P. elongatum exhibited the best effect on conidia susceptibility. The active compounds identified through statistical integration and subsequent isolation were piperaduncin C, asebogenin and (−)-methyllinderatin. These findings indicated that the integrative, indirect approach is useful for the identification of bioactive metabolites from botanical extracts to be further used as biological protective agents against this phytopathogen.
Optimization of the Multienzyme-Assisted Extraction Procedure of Bioactive Compounds Extracts from Common Buckwheat (Fagopyrum esculentum M.) and Evaluation of Obtained Extracts
Authors: Štreimikytė Paulina , Urbonavičienė Dalia , Balčiūnaitienė Aistė , Viškelis Pranas , Viškelis Jonas
Published: December 2021

Optimization of the extraction procedure using a multienzymes cocktail for common buckwheat (Fagopyrum esculentum M.) is important due to the yield, fermentable sugars, oligosaccharides and bioactive compounds for creating higher added value products. This study was undertaken to find out the optimum multienzymes-water extraction on yield and total phenolic compounds for common Buckwheat using response surface methodology (RSM). Three independent variables, time (2, 13, and 24 h), temperature (60 °C, 70 °C, 80 °C), and non-starch polysaccharide (NSP) enzymes mixture (0.10, 0.55, and 1.00 mL), were analyzed to optimize the response variables. NSP hydrolyzing enzymes, cellulase, xylanase, and β-glucanase, were produced by Trichoderma reesei. Estimated optimum conditions for F. esculentum were found: time—2 h, temperature—65 °C, and cellulase activity—8.6 CellG5 Units/mL. Different optimization run samples were collected and lyophilized for further analysis until the hydrophilic property using the water contact angle methodology and rutin content using HPLC was determined. Results indicated NSP enzymes activity did not differ between water contact angles after 13 h of enzymatic water extraction. However, longer fermentation time (24 h) decreased static water contact angle by approximately 3–7° for lyophilized water extract and 2–7° for solid fraction after fermentation. It implies enzymatic hydrolysis during water extraction increased hydrophilic properties in solid fraction and decreased hydrophilicity in water fraction due to the enzymes cleaved glycosidic bonds releasing water-soluble compounds.
Proteomics and Interspecies Interaction Analysis Revealed Abscisic Acid Signalling to Be the Primary Driver for Oil Palm’s Response against Red Palm Weevil Infestation
Authors: Harith-Fadzilah Nazmi , Lam Su Datt , Haris-Hussain Mohammad , Ghani Idris Abd , Zainal Zamri , Jalinas Johari , Hassan Maizom
Published: December 2021

The red palm weevil (RPW; Rhynchophorus ferrugineus Olivier (Coleoptera Curculionidae)) is an invasive insect pest that is difficult to manage due to its nature of infesting the host palm trees from within. A holistic, molecular-based approach to identify proteins that correlate with RPW infestation could give useful insights into the vital processes that are prevalent to the host’s infestation response and identify the potential biomarkers for an early detection technique. Here, a shotgun proteomic analysis was performed on oil palm (Elaeis guineensis; OP) under untreated (control), wounding by drilling (wounded), and artificial larval infestation (infested) conditions at three different time points to characterise the RPW infestation response at three different stages. KEGG pathway enrichment analysis revealed many overlapping pathways between the control, wounded, and infested groups. Further analysis via literature searches narrowed down biologically relevant proteins into categories, which were photosynthesis, growth, and stress response. Overall, the patterns of protein expression suggested abscisic acid (ABA) hormone signalling to be the primary driver of insect herbivory response. Interspecies molecular docking analysis between RPW ligands and OP receptor proteins provided putative interactions that result in ABA signalling activation. Seven proteins were selected as candidate biomarkers for early infestation detection based on their relevance and association with ABA signalling. The MS data are available via ProteomeXchange with identifier PXD028986. This study provided a deeper insight into the mechanism of stress response in OP in order to develop a novel detection method or improve crop management.
Grey and Black Anti-Hail Nets Ameliorated Apple (Malus × domestica Borkh. cv. Golden Delicious) Physiology under Mediterranean Climate
Authors: Brito Cátia , Rodrigues Manuel Ângelo , Pinto Luís , Gonçalves Alexandre , Silva Ermelinda , Martins Sandra , Rocha Luis , Pavia Ivo , Arrobas Margarida , Ribeiro António Castro , Moutinho-Pereira José , Correia Carlos M.
Published: December 2021

The use of anti-hail nets on orchards changes the microclimate underneath the net. This might be of great importance in apple growing regions characterized by high radiation levels and hot and dry climates during the summer season. But, depending on the net colour and on the local climatic conditions, the shade promoted triggers different responses by the trees. Grey and black anti-hail nets were applied in an apple orchard (cv. ‘Golden Delicious’) located in Northeast Portugal. Under the nets a lower concentration of glomalin related-soil proteins was observed, along with an improvement on trees water status, stomatal conductance, net photosynthetic rate, total chlorophylls, N, Mg, Fe and Cu concentrations, as well as an increase in mean fruit weight. The major difference between nets was on the photosynthetic efficiency, being higher on black net in sunny days, while grey net performed better under cloudy conditions. The use of netting systems proved to be effective in improving “Golden Delicious” apple trees performance under a Mediterranean climate, mainly when the radiation reaching the plants surpass the tree saturation point for photosynthesis. Therefore, these findings anticipate solutions for current and forecasted negative effects of climate change.
The Influence of Climate Warming and Humidity on Plant Diversity and Soil Bacteria and Fungi Diversity in Desert Grassland
Authors: Zhang Yi , Xie Yingzhong , Ma Hongbin , Zhang Juan , Jing Le , Wang Yutao , Li Jianping
Published: December 2021

Our study, which was conducted in the desert grassland of Ningxia in China (E 107.285, N 37.763), involved an experiment with five levels of annual precipitation 33% (R33), 66% (R66), 100% (CK), 133% (R133), 166% (R166) and two temperature levels (inside Open-Top Chamber (OTC) and outside OTC). Our objective was to determine how plant, soil bacteria, and fungi diversity respond to climate change. Our study suggested that plant α-diversity in CK and TCK were significantly higher than that of other treatments. Increased precipitation promoted root biomass (RB) growth more than aboveground living biomass (ALB). R166 promoted the biomass of Agropyron mongolicum the most. In the fungi communities, temperature and precipitation interaction promoted α-diversity. In the fungi communities, the combination of increased temperature and natural precipitation (TCK) promoted β-diversity the most, whose distance was determined to be 25,124 according to PCA. In the bacteria communities, β-diversity in CK was significantly higher than in other treatments, and the distance was determined to be 3010 according to PCA. Soil bacteria and fungi α- and β-diversity, and ALB promoted plant diversity the most. The interactive effects of temperature and precipitation on C, N, and P contents of plants were larger than their independent effects.