bluuebunny/crossref_metadata_2025 huggingface dataset:
Reservoir-Style Polymeric Drug Delivery Systems: Empirical and Predictive Models for Implant Design
Authors: Li Linying , Lee Chanhwa , Cruz Daniela , Krovi Sai , Hudgens Michael , Cottrell Mackenzie , Johnson Leah
Published: October 2022

Controlled drug delivery systems can provide sustained release profiles, favorable pharmacokinetics, and improved patient adherence. Here, a reservoir-style implant comprising a biodegradable polymer, poly(ε-caprolactone) (PCL), was developed to deliver drugs subcutaneously. This work addresses a key challenge when designing these implantable drug delivery systems, namely the accurate prediction of drug release profiles when using different formulations or form factors of the implant. The ability to model and predict the release behavior of drugs from an implant based on their physicochemical properties enables rational design and optimization without extensive and laborious in vitro testing. By leveraging experimental observations, we propose a mathematical model that predicts the empirical parameters describing the drug diffusion and partitioning processes based on the physicochemical properties of the drug. We demonstrate that the model enables an adequate fit predicting empirical parameters close to experimental values for various drugs. The model was further used to predict the release performance of new drug formulations from the implant, which aligned with experimental results for implants exhibiting zero-order release kinetics. Thus, the proposed empirical models provide useful tools to inform the implant design to achieve a target release profile.
Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters
Authors: Jasenovec Tomas , Radosinska Dominika , Kollarova Marta , Vrbjar Norbert , Balis Peter , Trubacova Simona , Paulis Ludovit , Tothova Lubomira , Shawkatova Ivana , Radosinska Jana
Published: October 2022

The objective of our study was to contribute to the characterization of monocrotaline-induced pulmonary arterial hypertension (PAH) in a rat model, with emphasis on the renin–angiotensin–aldosterone system, parameters of oxidative stress, the activity of matrix metalloproteinases, and erythrocyte parameters. Moreover, we aimed to analyze the effects of bosentan. Experiments were performed on 12-week-old male Wistar rats randomly assigned to 3 groups: control, monocrotaline-treated (60 mg/kg), and monocrotaline combined with bosentan (300 mg/kg/day). Our study confirmed the well-known effects of monocrotaline administration on lungs and the right ventricle, as well as pulmonary arterial pressure. In addition, we observed activation of the alternative pathway of the renin–angiotensin system, namely an increase in angiotensin (Ang) 1–7 and Ang 1-5 together with an increase in Ang I, but without any change in Ang II level, and downregulation of aldosterone 4 weeks after monocrotaline administration. For the first time, modifications of erythrocyte Na,K-ATPase enzyme kinetics were demonstrated as well. Our observations do not support data obtained in PAH patients showing an increase in Ang II levels, increase in oxidative stress, and deterioration in RBC deformability. Although bosentan primarily targets the vascular smooth muscle, our study confirmed its antioxidant effect. The obtained data suggest that besides the known action of bosentan, it decreases heart rate and increases erythrocyte deformability, and hence could have a beneficial hemodynamic effect in the PAH condition.
Evaluating and Improving Neonatal Gentamicin Pharmacokinetic Models Using Aggregated Routine Clinical Care Data
Authors: Tong Dominic M. H. , Hughes Jasmine H. , Keizer Ron J.
Published: October 2022

Model-informed precision dosing (MIPD) can aid dose decision-making for drugs such as gentamicin that have high inter-individual variability, a narrow therapeutic window, and a high risk of exposure-related adverse events. However, MIPD in neonates is challenging due to their dynamic development and maturation and by the need to minimize blood sampling due to low blood volume. Here, we investigate the ability of six published neonatal gentamicin population pharmacokinetic models to predict gentamicin concentrations in routine therapeutic drug monitoring from nine sites in the United State (n = 475 patients). We find that four out of six models predicted with acceptable levels of error and bias for clinical use. These models included known important covariates for gentamicin PK, showed little bias in prediction residuals over covariate ranges, and were developed on patient populations with similar covariate distributions as the one assessed here. These four models were refit using the published parameters as informative Bayesian priors or without priors in a continuous learning process. We find that refit models generally reduce error and bias on a held-out validation data set, but that informative prior use is not uniformly advantageous. Our work informs clinicians implementing MIPD of gentamicin in neonates, as well as pharmacometricians developing or improving PK models for use in MIPD.
Advances in the Application of Nanomaterials to the Treatment of Melanoma
Authors: Wang Zeqi , Yu Yu , Wang Chuqiao , Li Jin , Pang Yan
Published: October 2022

Melanoma can be divided into cutaneous melanoma, uveal melanoma, mucosal melanoma, etc. It is a very aggressive tumor that is prone to metastasis. Patients with metastatic melanoma have a poor prognosis and shorter survival. Although current melanoma treatments have been dramatically improved, there are still many problems such as systemic toxicity and the off-target effects of drugs. The use of nanoparticles may overcome some inadequacies of current melanoma treatments. In this review, we summarize the limitations of current therapies for cutaneous melanoma, uveal melanoma, and mucosal melanoma, as well as the adjunct role of nanoparticles in different treatment modalities. We suggest that nanomaterials may have an effective intervention in melanoma treatment in the future.
Iron-Based Magnetic Nanosystems for Diagnostic Imaging and Drug Delivery: Towards Transformative Biomedical Applications
Authors: Bossmann Stefan H. , Payne Macy M. , Kalita Mausam , Bristow Reece M. D. , Afshar Ayda , Perera Ayomi S.
Published: October 2022

The advancement of biomedicine in a socioeconomically sustainable manner while achieving efficient patient-care is imperative to the health and well-being of society. Magnetic systems consisting of iron based nanosized components have gained prominence among researchers in a multitude of biomedical applications. This review focuses on recent trends in the areas of diagnostic imaging and drug delivery that have benefited from iron-incorporated nanosystems, especially in cancer treatment, diagnosis and wound care applications. Discussion on imaging will emphasise on developments in MRI technology and hyperthermia based diagnosis, while advanced material synthesis and targeted, triggered transport will be the focus for drug delivery. Insights onto the challenges in transforming these technologies into day-to-day applications will also be explored with perceptions onto potential for patient-centred healthcare.
Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review
Authors: Démaris Alix , Widigson Ella S. K. , Ilvemark Johan F. K. F. , Steenholdt Casper , Seidelin Jakob B. , Huisinga Wilhelm , Michelet Robin , Aulin Linda B. S. , Kloft Charlotte
Published: October 2022

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.
Acute Effects of Intratumor DNA Electrotransfer
Authors: Bhandary Manya , Sales Conniff Amanda , Miranda Kaitlyn , Heller Loree C.
Published: October 2022

Intratumor therapeutic DNA electroporation or electrotransfer is in clinical trials in the United States and is under development in many other countries. Acute changes in endogenous gene expression in response to DNA or to pulse application may significantly modulate the therapeutic efficacy of the expressed proteins. Oligonucleotide arrays were used in this study to quantify changes in mRNA expression in B16-F10 mouse melanoma tumors four hours after DNA electrotransfer. The data were subjected to the DAVID v6.8 web server for functional annotation to reveal regulated genes and genetic pathways. Gene ontology analysis revealed several molecular functions related to cytoskeletal remodeling and inflammatory signaling. In B16-F10 cells, F-actin remodeling was confirmed by phalloidin staining in cells that received pulse application alone or in the presence of DNA. Chemokine secretion was confirmed in cells receiving DNA electrotransfer. These results indicate that pulse application alone or in the presence of DNA may modulate the therapeutic efficacy of therapeutic DNA electrotransfer.
Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms
Authors: Hartzke David , Pössl Axel , Schlupp Peggy , Runkel Frank E.
Published: October 2022

Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.
Analytical Evaluation of Wet and Dry Mechanochemical Syntheses of Calcium-Deficient Hydroxyapatite Containing Zinc Using X-ray Diffractometry and Near-Infrared Spectroscopy
Authors: Otsuka Makoto , Saito Hanae , Sasaki Tetsuo
Published: October 2022

Calcium-deficient zinc-containing calcium phosphate (ZnAP), which has sustained zinc release properties that are effective for treating osteoporosis, can be efficiently synthesized as a biomaterial through wet grinding. To elucidate the physicochemical mechanism of these mechanochemical syntheses, ground products were obtained from the starting material powder (S-CP), consisting of calcium hydrogen phosphate dihydrate (CHPD), calcium oxide (CaO), and zinc oxide (ZnO), by wet and dry grinding for 0–3 h in a centrifugal ball mill. The ground S-CP products were analyzed using powder X-ray diffraction (XRD) and near-infrared spectroscopy (NIRS); the crystal transformations and molecular interactions of the ground products were kinetically analyzed. The XRD and second-derivative NIRS results indicate that the S-CP is primarily transformed into ZnAP via amorphous solid formation in wet grinding, and the reaction follows a consecutive reaction model. In contrast, in dry grinding, the ground product of CHPD and CaO is transformed into an amorphous solid following an equilibrium reaction model; however, ZnO is predominantly not transformed and remains crystalline.
Implementation and Cross-Validation of a Pharmacokinetic Model for Precision Dosing of Busulfan in Hematopoietic Stem Cell Transplanted Children
Authors: Goutelle Sylvain , Thoma Yann , Buffet Roxane , Philippe Michael , Buclin Thierry , Guidi Monia , Csajka Chantal
Published: October 2022

Busulfan, a drug used in conditioning prior to hematopoietic stem cell transplantation (HSCT) in children, has a narrow therapeutic margin. The model-informed precision dosing (MIPD) of busulfan is desirable, but there is a lack of validated tools. The objective of this study was to implement and cross-validate a population pharmacokinetic (PK) model in the Tucuxi software for busulfan MIPD in HSCT children. A search of the literature was performed to identify candidate population PK models. The goodness of fit of three selected models was assessed in a dataset of 178 children by computing the mean error (ME) and root-mean-squared error of prediction (RMSE). The best model was implemented in Tucuxi. The individual predicted concentrations, the area under the concentration-time curve (AUC), and dosage requirements were compared between the Tucuxi model and a reference model available in the BestDose software in a subset of 61 children. The model from Paci et al. best fitted the data in the full dataset. In a subset of 61 patients, the predictive performance of Tucuxi and BestDose models was comparable with ME values of 6.4% and −2.5% and RMSE values of 11.4% and 13.6%, respectively. The agreement between the estimated AUC and the predicted dose was good, with 6.6% and 4.9% of the values being out of the 95% limits of agreement, respectively. To conclude, a PK model for busulfan MIPD was cross-validated and is now available in the Tucuxi software.
Preparation of pH-Responsive Hydrogels Based on Chondroitin Sulfate/Alginate for Oral Drug Delivery
Authors: Suhail Muhammad , Ullah Hamid , Vu Quoc Lam , Khan Arshad , Tsai Ming-Jun , Wu Pao-Chu
Published: October 2022

This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N′,N′-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine.
Doxorubicin-Loaded Polymeric Micelles Conjugated with CKR- and EVQ-FLT3 Peptides for Cytotoxicity in Leukemic Stem Cells
Authors: Chueahongthong Fah , Tima Singkome , Chiampanichayakul Sawitree , Dejkriengkraikul Pornngarm , Okonogi Siriporn , Sasarom Mathurada , Rodwattanagul Soraya , Berkland Cory , Anuchapreeda Songyot
Published: October 2022

Doxorubicin (Dox) is the standard chemotherapeutic agent for acute myeloblastic leukemia (AML) treatment. However, 40% of Dox-treated AML cases relapsed due to the presence of leukemic stem cells (LSCs). Thus, poloxamer 407 and CKR- and EVQ-FLT3 peptides were used to formulate Dox-micelles (DMs) and DM conjugated with peptides (CKR and EVQ) for improving AML-LSC treatment. Results indicated that DMs with a weight ratio of Dox to P407 of 1:200 had a particle size of 23.3 ± 1.3 nm with a high percentage of Dox entrapment. They were able to prolong drug release and maintain physicochemical stability. Following effective DM preparation, P407 was modified and conjugated with FLT3 peptides, CKR and EVQ to formulate DM-CKR, DM-EVQ, and DM-CKR+DM-EVQ. Freshly synthesized DMs displaying FLT3 peptides showed particle sizes smaller than 50 nm and a high drug entrapment level, comparable with DMs. DM-CKR+DM-EVQ was considerably more toxic to KG-1a (AML LSC-like cell model) than Dox-HCl. These FLT3-targeted DMs could increase drug uptake and induce apoptosis induction. Due to an increase in micelle-LSC binding and uptake, DMs displaying both peptides tended to improve the potency of Dox compared to a single peptide-coupled micelle.
High Incidence of Intracerebral Hemorrhaging Associated with the Application of Low-Intensity Focused Ultrasound Following Acute Cerebrovascular Injury by Intracortical Injection
Authors: Kim Evgenii , Van Reet Jared , Kim Hyun-Chul , Kowsari Kavin , Yoo Seung-Schik
Published: October 2022

Low-intensity transcranial focused ultrasound (FUS) has gained momentum as a non-/minimally-invasive modality that facilitates the delivery of various pharmaceutical agents to the brain. With the additional ability to modulate regional brain tissue excitability, FUS is anticipated to confer potential neurotherapeutic applications whereby a deeper insight of its safety is warranted. We investigated the effects of FUS applied to the rat brain (Sprague-Dawley) shortly after an intracortical injection of fluorescent interstitial solutes, a widely used convection-enhanced delivery technique that directly (i.e., bypassing the blood–brain-barrier (BBB)) introduces drugs or interstitial tracers to the brain parenchyma. Texas Red ovalbumin (OA) and fluorescein isothiocyanate-dextran (FITC-d) were used as the interstitial tracers. Rats that did not receive sonication showed an expected interstitial distribution of OA and FITC-d around the injection site, with a wider volume distribution of OA (21.8 ± 4.0 µL) compared to that of FITC-d (7.8 ± 2.7 µL). Remarkably, nearly half of the rats exposed to the FUS developed intracerebral hemorrhaging (ICH), with a significantly higher volume of bleeding compared to a minor red blood cell extravasation from the animals that were not exposed to sonication. This finding suggests that the local cerebrovascular injury inflicted by the micro-injection was further exacerbated by the application of sonication, particularly during the acute stage of injury. Smaller tracer volume distributions and weaker fluorescent intensities, compared to the unsonicated animals, were observed for the sonicated rats that did not manifest hemorrhaging, which may indicate an enhanced degree of clearance of the injected tracers. Our results call for careful safety precautions when ultrasound sonication is desired among groups under elevated risks associated with a weakened or damaged vascular integrity.
Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy
Authors: Cho Hanhee , Shim Man Kyu , Moon Yujeong , Song Sukyung , Kim Jinseong , Choi Jiwoong , Kim Jeongrae , Lee Youngjoo , Park Jung Yeon , Kim Yongju , Ahn Cheol-Hee , Kim Mi Ra , Yoon Hong Yeol , Kim Kwangmeyung
Published: October 2022

A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine.
Aqueous Prostaglandin Eye Drop Formulations
Authors: Jansook Phatsawee , Loftsson Thorsteinn
Published: October 2022

Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects. Here the physiochemical properties and chemical stabilities of the commercially available PGAs are reviewed, and the compositions of their eye drop formulations are discussed. Furthermore, the novel PGA formulations for glaucoma treatment are reviewed.
Guanfacine Normalizes the Overexpression of Presynaptic α-2A Adrenoceptor Signaling and Ameliorates Neuropathic Pain in a Chronic Animal Model of Type 1 Diabetes
Authors: Munawar Neha , Nader Joelle , Khadadah Najat H. , Al Madhoun Ashraf , Al-Ali Waleed , Varghese Linu A. , Masocha Willias , Al-Mulla Fahd , Bitar Milad S.
Published: October 2022

Background: Diabetes is associated with several complications, including neuropathic pain, which is difficult to manage with currently available drugs. Descending noradrenergic neurons possess antinociceptive activity; however, their involvement in diabetic neuropathic pain remains to be explored. Methods: To infer the regulatory role of this system, we examined as a function of diabetes, the expression and localization of alpha-2A adrenoceptors (α2-AR) in the dorsal root ganglia and key regions of the central nervous system, including pons and lumbar segment of the spinal cord using qRT-PCR, Western blotting, and immunofluorescence-based techniques. Results: The data revealed that presynaptic synaptosomal-associated protein-25 labeled α2-AR in the central and peripheral nervous system of streptozotocin diabetic rats was upregulated both at the mRNA and protein levels. Interestingly, the levels of postsynaptic density protein-95 labeled postsynaptic neuronal α2-AR remained unaltered as a function of diabetes. These biochemical abnormalities in the noradrenergic system of diabetic animals were associated with increased pain sensitivity as typified by the presence of thermal hyperalgesia and cold/mechanical allodynia. The pain-related behaviors were assessed using Hargreaves apparatus, cold-plate and dynamic plantar aesthesiometer. Chronically administered guanfacine, a selective α2-AR agonist, to diabetic animals downregulated the upregulation of neuronal presynaptic α2-AR and ameliorated the hyperalgesia and the cold/mechanical allodynia in these animals. Conclusion: Together, these findings demonstrate that guanfacine may function as a potent analgesic and highlight α2-AR, a key component of the descending neuronal autoinhibitory pathway, as a potential therapeutic target in the treatment of diabetic neuropathic pain.
Exotic Grasses Reduce Infiltration and Moisture Availability in a Temperate Oak Savanna
Authors: Gedalof Ze’ev , Davy Lesley E. , Berg Aaron
Published: October 2022

Biological invasions represent one of the most urgent conservation challenges. Oregon white oak (Quercus garryana) savannas, a complex of grassland and transitional forest, are especially sensitive to these invasions. These ecosystems have been severely degraded and fragmented over the past century and are being encroached by conifers, and oak seedlings are failing to emerge from the understory at many locations. Understanding competitive interactions between Oregon white oak and associated native and exotic vegetation would provide insight into forest-grassland dynamics and the role of exotic grasses in the decline of native species, the processes that maintain temperate savanna ecosystems, and the role of soil water uptake by individual savanna species in contributing to overall species assemblages. In this study, we quantified the soil moisture budget for invaded and uninvaded oak-associated ecosystems. From February to October 2007 we used a split paired plot experiment in Duncan, British Columbia, Canada to measure soil moisture on treatment sites where exotic grasses were removed with herbicide and control plots where they were not, using three depths (5, 20, and 35 or 50 cm) in the soil profile. Our results show that the plots that contained exotic vegetation had a faster rate of soil drying following precipitation events at the 5 cm depth than plots with the predominantly native species. We attribute this difference to the capacity of exotic vegetation to exploit soil moisture more rapidly than native vegetation at times of the year when native vegetation cannot. These results provide insight into one mechanism by which exotic grasses affect associated native plants and could help guide restoration efforts.
The Pattern of Rare Earth Elements Like a Possible Helpful Tool in Traceability and Geographical Characterization of the Soil-Olive System (Olea europaea L.)
Authors: Barbera Marcella , Saiano Filippo , Tutone Livia , Massenti Roberto , Pisciotta Antonino
Published: October 2022

The identification of a product, with its geographical origin, is a guaranty of the value of the foodstuff and protection from potential fraud. Extra virgin olive oil is produced or marketed as a single variety or a blend of two or more cultivars, often of different geographic origins. Therefore, to study a possible link between the soil and olive oil, we accounted crucial to analyse the behaviour of olive of different cultivars. We studied Rare Earth Elements (REE) amounts and their relationship to trace their distribution from soil to the olive pulp (Olea europea L.). The results obtained pointed out that the different cultivars of Olea did not drive significant differences in reciprocal ratios of REE in the uptake from the soil up to olive (except for Eu). However soil-plant Rare Earth relationships depend exclusively on the soil REE composition. This method can be the starting point to enforcing the laws, in fact, it is important to develop analytical methods to measure the authenticity of the samples, and to verify the geographical origin even when olive oil is blended.
Amplified Drought Alters Leaf Litter Metabolome, Slows Down Litter Decomposition, and Modifies Home Field (Dis)Advantage in Three Mediterranean Forests
Authors: Quer Elodie , Pereira Susana , Michel Thomas , Santonja Mathieu , Gauquelin Thierry , Simioni Guillaume , Ourcival Jean-Marc , Joffre Richard , Limousin Jean-Marc , Aupic-Samain Adriane , Lecareux Caroline , Dupouyet Sylvie , Orts Jean-Philippe , Bousquet-Mélou Anne , Gros Raphaël , Sagova-Mareckova Marketa , Kopecky Jan , Fernandez Catherine , Baldy Virginie
Published: October 2022

In Mediterranean ecosystems, the projected rainfall reduction of up to 30% may alter plant–soil interactions, particularly litter decomposition and Home Field Advantage (HFA). We set up a litter transplant experiment in the three main forests encountered in the northern part of the Medi-terranean Basin (dominated by either Quercus ilex, Quercus pubescens, or Pinus halepensis) equipped with a rain exclusion device, allowing an increase in drought either throughout the year or concentrated in spring and summer. Senescent leaves and needles were collected under two precipitation treatments (natural and amplified drought plots) at their “home” forest and were left to decompose in the forest of origin and in other forests under both drought conditions. MS-based metabolomic analysis of litter extracts combined with multivariate data analysis enabled us to detect modifications in the composition of litter specialized metabolites, following amplified drought treatment. Amplified drought altered litter quality and metabolomes, directly slowed down litter decomposition, and induced a loss of home field (dis)advantage. No indirect effect mediated by a change in litter quality on decomposition was observed. These results may suggest major alterations of plant–soil interactions in Mediterranean forests under amplified drought conditions.
The Structural, Biological, and In-Silico Profiling of Novel Capryloyl Tetra-Glucoside and Aliphatic Ester Constituents from the Abutilon indicum Offers New Perspectives on the Treatment of Pain and Inflammation
Authors: Wahab Shadma , Alsayari Abdulrhman , Muhsinah Abdullatif Bin , Almaghaslah Dalia , Haque Anzarul , Khalid Mohammad , Alnasser Sulaiman Mohammed , Azam Faizul , Hussain Md. Sarfaraj
Published: October 2022

Abutilon indicum L. (Malvaceae), more often referred to as Peeli booti, Kanghi, and Kakhi, is a perennial shrub found in many countries of Asia. Traditionally, this plant is used as a diuretic to treat inflammation, discomfort, urethral infections, and gout. Inflammation and pain are key topics of interest for researchers throughout the globe, since they are linked to almost every illness that could affect humans or animals. The present study was conducted to isolate the phytoconstituents from the methanolic extract of Abutilon indicum collected from the Bihar state Koshi river belt in India, and to evaluate the isolated phytoconstituents’ ability to reduce nociception and inflammation. Furthermore, molecular docking was performed to investigate the molecular interaction profile, with possible therapeutic targets for anti-inflammatory medicines. A. indicum methanolic extract yielded two novel phytocompounds identified as 5′-hydroxyhexyl n-hexadecanoate (AB-01) and n-octanoyl-β-D-glucopyranosyl-(2′-1′′)-β-D-glucopyranosyl-(2′′-1′′′)-β-D-glucopyranosyl-(2′′′-1′′′′)-β-D-glucopyranoside (AB-05), together with three previously recognized phytocompounds such as ester glucoside. All isolated molecules were tested for the efficacy of analgesic and anti-inflammatory characteristics at doses of 5 and 10 mg/kg body weight. The isolated compound’s molecular interaction profile with anti-inflammatory drug targets cyclooxygenase-2 and tumor necrosis factor-alpha possessed high potential energy in molecular docking. These findings may aid in developing anti-inflammatory and analgesic drugs from A. indicum.
Agro-Morphological and Cytogenetic Characterization of Colchicine-Induced Tetraploid Plants of Polemonium caeruleum L. (Polemoniaceae)
Authors: Samatadze Tatiana E. , Yurkevich Olga Yu. , Khazieva Firdaus M. , Basalaeva Irina V. , Konyaeva Elena A. , Burova Alla E. , Zoshchuk Svyatoslav A. , Morozov Alexander I. , Amosova Alexandra V. , Muravenko Olga V.
Published: October 2022

Polemonium caeruleum L. (Polemoniaceae) is a valuable medicinal herb with a wide spectrum of biological activities. Under natural conditions, the productivity of this species is rather low. In this study, colchicine-induced tetraploid plants (2n = 4x = 36) of P. caeruleum were obtained, and for the first time, their morphological and cytogenetic characterization was performed. In the tetraploid plants, raw material productivity and also the content of triterpene saponins were significantly higher than in the control diploids. The analysis of chromosome behavior at meiosis and FISH chromosome mapping of 45S and 5S rDNA generally demonstrated stability of both genomes in the tetraploid plants. Based on chromosome morphology and distribution patterns of the studied molecular cytogenetic markers, all chromosome pairs in karyotypes were identified, and chromosome karyograms and idiograms of P. caeruleum were constructed. The revealed specific microdiagnostic characteristics of P. caeruleum (strongly sinuous cells and anomocytic stomata of the leaf epidermis, and also glandular hairs along the veins) could be useful for raw material identification. In the obtained tetraploids, the predominance of large stomata on the lower leaf epidermis was determined. The studied tetraploids can be used in various breeding programs to obtain high-quality pharmaceutical raw materials of P. caeruleum.
Nanofertilizers: A Smart and Sustainable Attribute to Modern Agriculture
Authors: Nongbet Amilia , Mishra Awdhesh Kumar , Mohanta Yugal Kishore , Mahanta Saurov , Ray Manjit Kumar , Khan Maryam , Baek Kwang-Hyun , Chakrabartty Ishani
Published: October 2022

The widespread use of fertilizers is a result of the increased global demand for food. The commonly used chemical fertilizers may increase plant growth and output, but they have deleterious effects on the soil, the environment, and even human health. Therefore, nanofertilizers are one of the most promising solutions or substitutes for conventional fertilizers. These engineered materials are composed of nanoparticles containing macro- and micronutrients that are delivered to the plant rhizosphere in a regulated manner. In nanofertilizers, the essential minerals and nutrients (such as N, P, K, Fe, and Mn) are bonded alone or in combination with nano-dimensional adsorbents. This review discusses the development of nanotechnology-based smart and efficient agriculture using nanofertilizers that have higher nutritional management, owing to their ability to increase the nutrient uptake efficiency. Additionally, the synthesis and mechanism of action of the nanofertilizers are discussed, along with the different types of fertilizers that are currently available. Furthermore, sustainable agriculture can be realised by the targeted delivery and controlled release of nutrients through the application of nanoscale active substances. This paper emphasises the successful development and safe application of nanotechnology in agriculture; however, certain basic concerns and existing gaps in research need to be addressed and resolved.
Transcriptome Analysis of Early Senescence in the Post-Anthesis Flag Leaf of Wheat (Triticum aestivum L.)
Authors: Lei Ling , Wu Dan , Cui Chao , Gao Xiang , Yao Yanjie , Dong Jian , Xu Liangsheng , Yang Mingming
Published: October 2022

Flag leaf senescence is an important determinant of wheat yield, as leaf senescence occurs in a coordinated manner during grain filling. However, the biological process of early senescence of flag leaves post-anthesis is not clear. In this study, early senescence in wheat was investigated using a high-throughput RNA sequencing technique. A total of 4887 differentially expressed genes (DEGs) were identified, and any showing drastic expression changes were then linked to particular biological processes. A hierarchical cluster analysis implied potential relationships between NAC genes and post-anthesis senescence in the flag leaf. In addition, a large set of genes associated with the synthesis; transport; and signaling of multiple phytohormones (JA, ABA, IAA, ET, SA, BR, and CTK) were expressed differentially, and many DEGs related to ABA and IAA were identified. Our results provide insight into the molecular processes taking place during the early senescence of flag leaves, which may provide useful information in improving wheat yield in the future.
The C-Terminal Region of SLIM1 Transcription Factor Is Required for Sulfur Deficiency Response
Authors: Piotrowska Justyna , Jodoi Yuki , Trang Nguyen Ha , Wawrzynska Anna , Takahashi Hideki , Sirko Agnieszka , Maruyama-Nakashita Akiko
Published: October 2022

Sulfur LIMitation1 (SLIM1) transcription factor coordinates gene expression in plants in response to sulfur deficiency (−S). SLIM1 belongs to the family of plant-specific EIL transcription factors with EIN3 and EIL1, which regulate the ethylene-responsive gene expression. The EIL domains consist of DNA binding and dimerization domains highly conserved among EIL family members, while the N- and C-terminal regions are structurally variable and postulated to have regulatory roles in this protein family, such that the EIN3 C-terminal region is essential for its ethylene-responsive activation. In this study, we focused on the roles of the SLIM1 C-terminal region. We examined the transactivation activity of the full-length and the truncated SLIM1 in yeast and Arabidopsis. The full-length SLIM1 and the truncated form of SLIM1 with a deletion of C-terminal 106 amino acids (ΔC105) transactivated the reporter gene expression in yeast when they were fused to the GAL4 DNA binding domain, whereas the deletion of additional 15 amino acids to remove the C-terminal 120 amino acids (ΔC120) eliminated such an activity, identifying the necessity of that 15-amino-acid segment for transactivation. In the Arabidopsis slim1-2 mutant, the transcript levels of SULTR1;2 sulfate transporter and the GFP expression derived from the SULTR1;2 promoter-GFP (PSULTR1;2-GFP) transgene construct were restored under −S by introducing the full-length SLIM1, but not with the C-terminal truncated forms ΔC105 and ΔC57. Furthermore, the transcript levels of −S-responsive genes were restored concomitantly with an increase in glutathione accumulation in the complementing lines with the full-length SLIM1 but not with ΔC57. The C-terminal 57 amino acids of SLIM1 were also shown to be necessary for transactivation of a −S-inducible gene, SHM7/MSA1, in a transient expression system using the SHM7/MSA1 promoter-GUS as a reporter. These findings suggest that the C-terminal region is essential for the SLIM1 activity.
Foliar Application of Different Iron Sources Improves Morpho-Physiological Traits and Nutritional Quality of Broad Bean Grown in Sandy Soil
Authors: Mahmoud Abdel Wahab M. , Ayad Amira A. , Abdel-Aziz Hend S. M. , Williams Leonard L. , El-Shazoly Rasha M. , Abdel-Wahab Ahmed , Abdeldaym Emad A.
Published: October 2022

Nano-fertilizers are a new tool that can be used to address plant production challenges, and it addresses such nutrient deficiencies through smart agriculture approaches. Iron (Fe) is a vital element for several metabolic and physiological processes; however, Fe deficiency is common in poorly fertile soils (sand soil) and in arid areas. Therefore, additional research is required to select the most efficient form of iron absorbance. This research was implemented on broad bean plants (Vicia faba L. var. major Harz) to examine the impact of three iron sources: nano-iron (FeNPs, T1), iron sulfate (T2), and chelated iron (T3) as a foliar spray on the morphological properties, physiological attributes, and nutritional status of these plants compared to the untreated plants (control). The obtained results showed that foliar spraying with FeNPs, chelated iron and sulphate iron fertilizers increased plant height by 35.01%, 26.2, and 20.4%; leaf area by 38.8%, 18.3%, and 8.1%; the fresh weight of the plant by 47%, 32.8%, and 7.3%; the dry weight of the plant by 52.9%, 37.3%, and 11.2%; and the number of branches by 47%, 31.3%, and 25.6 %, respectively, compared to the control treatment (CT). Furthermore, the application of FeNPs, chelated iron, and sulphate iron fertilizers improved the number of pods by 47.9%, 24.8%, and 6.1%; the number of seeds by 32.8%, 7.9%, and 2.8%; and seed weight by 20.8%, 9.1%, and 5.4%, compared to control treatment (CT). Additionally, foliar application of FeNPs showed the highest values of photosynthesis rate (Pn), water-use efficiency (WUE), total chlorophyll, and phytohormones (IAA, GA3) compared to all the other treatments. The anatomical structure revealed an enhancement of leaf size and thickness (epidermis cells and mesophyll tissue) affected by FeNPs treatment compared to other treatments. Foliar application of FeNPs also improved the total content of carbohydrates, crude protein, element content (N, P, K, Ca, Na, Fe, Zn, Mn, and Cu), and some amino acids such as lysine, arginine, phenylalanine, isoleucine, and tyrosine in the seeds of broad beans. Based on the above results, the maximum values of all tested measurements were observed when FeNPs were used as the foliar spraying followed by chelated and sulphate iron fertilizers. Therefore, these findings suggest that using FeNPs, as a foliar treatment, could be a promising strategy for reducing the Fe deficiency in sandy soil and enhancing plant growth, pod yield, and pod quality of broad bean plants in addition to being environmentally favored in arid areas.
Optimization of Management Zone Delineation for Precision Crop Management in an Intensive Farming System
Authors: Yuan Yifan , Shi Bo , Yost Russell , Liu Xiaojun , Tian Yongchao , Zhu Yan , Cao Weixing , Cao Qiang
Published: October 2022

Soil is characterized by high spatiotemporal variability due to the combined influence of internal and external factors. The most efficient approach for addressing spatial variability is the use of management zones (MZs). Common approaches for delineating MZs include K-means and fuzzy C-means cluster analysis algorithms. However, these clustering methods have been used to delineate MZs independent of the spatial dependence of soil variables. Thus, the accuracy of the clustering results has been limited. In this study, six soil variables (soil pH, total nitrogen, organic matter, available phosphorus, available potassium, and soil apparent electrical conductivity) were used to characterize the spatial variability within a representative village in Suining County, Jiangsu Province, China. Two variable reduction techniques (PCA, multivariate spatial analysis based on Moran’s index; MULTISPATI-PCA) and three different clustering algorithms (fuzzy C-means clustering, iterative self-organizing data analysis techniques algorithm, and Gaussian mixture model; GMM) were used to optimize the MZ delineation. Different clustering model composites were evaluated using yield data collected after the wheat harvest in 2020. The results indicated that the variable reduction technologies in conjunction with clustering algorithms provided better performance in MZ delineation, with average silhouette coefficient (ASC) and variance reduction (VR) of 0.48–0.57, and 13.35–23.13%, respectively. Moreover, the MULTISPATI-PCA approach was more conducive to identifying variables requiring MZ delineation than traditional PCA methods. Combining MULTISPATI-PCA and the GMM algorithm yielded the greatest VR and ASC values in this study. These results can guide the optimization of MZ delineation in intensive agricultural systems, thus enabling more precise nutrient management.
Biochemical Insights into the Ability of Lemna minor L. Extract to Counteract Copper Toxicity in Maize
Authors: Miras-Moreno Begoña , Senizza Biancamaria , Regni Luca , Tolisano Ciro , Proietti Primo , Trevisan Marco , Lucini Luigi , Rouphael Youssef , Del Buono Daniele
Published: October 2022

Metal trace elements (MTE) can damage crops if present in excessive amounts in the environment. This research investigated the effect of a plant extract of an aquatic species, Lemna minor L. (duckweed) (LE), on the ability of maize to cope with copper (Cu) toxicity. LE reversed the effects of Cu2+ on photosynthetic activity (Pn), evapotranspiration (E), stomatal conductance (gs), sub-stomatal CO2 concentration (Ci) and biomass which did not differ from the untreated controls. LE did not regulate the amount of copper in maize leaves, but compared to Cu-treated samples, the extract decreased the hydrogen peroxide (H2O2; −26% on average) and malondialdehyde (MDA; −47% on average) content, regardless of the dosage applied. Furthermore, the activity of antioxidant enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT) was significantly increased by LE compared to samples treated with Cu alone. Untargeted metabolomic profiling revealed that LE activated maize secondary metabolism, eliciting the content of non-enzymatic antioxidants (flavonoids, glutathione and glutathione-related compounds, tocopherols and tocotrienols) and modulating plant stress-related hormones (brassinosteroids and ABA derivatives). The results of this study are promising and pave the way for using duckweed as a biostimulant to trigger beneficial effects in maize and increase its resistance to MTEs.