bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Total Syntheses of Both Enantiomers of Plymuthipyranone B and Its Unnatural Analogues: Evaluation of anti-MRSA Activity and Its Chiral Discrimination
Authors: Moriyama Mizuki , Liu Xiaoxi , Enoki Yuki , Matsumoto Kazuaki , Tanabe Yoo
Published: September 2021

Chiral total syntheses of both enantiomers of the anti-MRSA active plymuthipyranone B and all of the both enantiomers of three unnatural and synthetic analogues were performed. These two pairs of four chiral compounds are composed of the same 3-acyl-5,6-dihydro-2H-pyran-2-one structure. The starting synthetic step utilized a privileged asymmetric Mukaiyama aldol addition using Ti(OiPr)4/(S)-BINOL or Ti(OiPr)4/(R)-BINOL catalysis to afford the corresponding (R)- and (S)-δ-hydroxy-β-ketoesters, respectively, with highly enantiomeric excess (>98%). Conventional lactone formation and successive EDCI-mediated C-acylation produced the desired products, (R)- and (S)-plymuthipyranones B and three (R)- and (S)- synthetic analogues, with an overall yield of 42–56% with a highly enantiomeric excess (95–99%). A bioassay of the anti-MRSA activity against ATCC 43300 and 33591 revealed that (i) the MICs of the synthetic analogues against ATCC 43300 and ATCC 33591 were between 2 and 16 and 4 and 16 μg/mL, respectively, and those of vancomycin (reference) were 1 μg/mL. (ii) The natural (S)-plymuthipyranone B exhibited significantly higher activity than the unnatural (R)-antipode against both AACCs. (iii) The natural (R)-plymuthipyranone B and (R)-undecyl synthetic analogue at the C6 position exhibited the highest activity. The present work is the first investigation of the SAR between chiral R and S forms of this chemical class.
Chicory Extracts and Sesquiterpene Lactones Show Potent Activity against Bacterial and Fungal Pathogens
Authors: Häkkinen Suvi T. , Soković Marina , Nohynek Liisa , Ćirić Ana , Ivanov Marija , Stojković Dejan , Tsitko Irina , Matos Melanie , Baixinho João P. , Ivasiv Viktoriya , Fernández Naiara , Nunes dos Santos Claudia , Oksman-Caldentey Kirsi-Marja
Published: September 2021

Chicory (Cichorium intybus L.) is an important industrial crop cultivated mainly to extract the dietary fiber inulin. However, chicory also contains bioactive compounds such as sesquiterpene lactones and certain polyphenols, which are currently discarded as waste. Plants are an important source of active pharmaceutical ingredients, including novel antimicrobials that are urgently needed due to the global spread of drug-resistant bacteria and fungi. Here, we tested different extracts of chicory for a range of bioactivities, including antimicrobial, antifungal and cytotoxicity assays. Antibacterial and antifungal activities were generally more potent in ethyl acetate extracts compared to water extracts, whereas supercritical fluid extracts showed the broadest range of bioactivities in our assays. Remarkably, the chicory supercritical fluid extract and a purified fraction thereof inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Pseudomonas aeruginosa IBRS P001. Chicory extracts also showed higher antibiofilm activity against the yeast Candida albicans than standard sesquiterpene lactone compounds. The cytotoxicity of the extracts was generally low. Our results may thus lead to the development of novel antibacterial and antifungal preparations that are both effective and safe for human use.
The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells
Authors: Devor Eric J. , Schickling Brandon M. , Lapierre Jace R. , Bender David P. , Gonzalez-Bosquet Jesus , Leslie Kimberly K.
Published: September 2021

Elevated expression of placenta-specific protein 1 (PLAC1) is associated with the increased proliferation and invasiveness of a variety of human cancers, including ovarian cancer. Recent studies have shown that the tumor suppressor p53 directly suppresses PLAC1 transcription. However, mutations in p53 lead to the loss of PLAC1 transcriptional suppression. Small molecules that structurally convert mutant p53 proteins to wild-type conformations are emerging. Our objective was to determine whether the restoration of the wild-type function of mutated p53 could rescue PLAC1 transcriptional suppression in tumors harboring certain TP53 mutations. Ovarian cancer cells OVCAR3 and ES-2, both harboring TP53 missense mutations, were treated with the p53 reactivator HO-3867. Treatment with HO-3867 successfully rescued PLAC1 transcriptional suppression. In addition, cell proliferation was inhibited and cell death through apoptosis was increased in both cell lines. We conclude that the use of HO-3867 as an adjuvant to conventional therapeutics in ovarian cancers harboring TP53 missense mutations could improve patient outcomes. Validation of this conclusion must, however, come from an appropriately designed clinical trial.
A Comparative Survey of Anti-Melanoma and Anti-Inflammatory Potential of Usnic Acid Enantiomers—A Comprehensive In Vitro Approach
Authors: Galanty Agnieszka , Zagrodzki Paweł , Gdula-Argasińska Joanna , Grabowska Karolina , Koczurkiewicz-Adamczyk Paulina , Wróbel-Biedrawa Dagmara , Podolak Irma , Pękala Elżbieta , Paśko Paweł
Published: September 2021

Usnic acid (UA) is a chiral lichen metabolite with an interesting pharmacological profile. The aim of this study was to compare the anti-melanoma effect of (+)-UA and (−)-UA in an in vitro model by studying their impact on the cells as well as the processes associated with cancer progression. The effect of UA enantiomers on the viability, proliferation, and invasive potential of three melanoma cell lines (HTB140, A375, WM793) was evaluated. Their interaction with a chemotherapeutic drug—doxorubicin was assessed by isobolographic analysis. Anti-inflammatory and anti-tyrosinase properties of (+)-UA and (−)-UA were also examined. Both UA enantiomers dose- and time-dependently decreased the viability of all three melanoma cell lines. Their synergistic effect with doxorubicin was observed on A375 cells. (+)-Usnic acid at a sub-cytotoxic dose strongly inhibited melanoma cells migration. Both UA enantiomers decreased the release of pro-inflammatory mediators. The cytotoxic effect of (+)-UA and (−)-UA depends greatly on the melanoma cell type; however, the overall anti-melanoma potential is perspective. Our results indicate that the strategy of combining usnic acid enantiomers with cytostatic drugs may be an interesting option to consider in combating melanoma; however, further studies are required.
Comparative In Vitro Evaluation of Commercial Periodontal Gels on Antibacterial, Biocompatibility and Wound Healing Ability
Authors: Munar-Bestard Marta , Llopis-Grimalt Maria Antonia , Ramis Joana Maria , Monjo Marta
Published: September 2021

In the last years, several studies testing commercial periodontal gels that contain chlorhexidine (CHX) or other antibacterial agents, have raised concerns regarding their cytotoxicity in periodontal tissues. We aimed at comparing the biocompatibility but also the efficacy as regards to the antibacterial and wound healing ability of different commercial periodontal gels. In vitro human gingival fibroblasts (GF) and a 3D model of human tissue equivalents of gingiva (GTE) were used under inflammatory conditions to evaluate wound closure, cytotoxicity and gene expression. Antibacterial effects were also investigated on Porphyromonas gingivalis growth, viability and gingipain activity. In GF and in the bacterial study, we found cytotoxic effects on GF and a high inhibition on bacterial growth rate in gels containing CHX, asiaticoside, enoxolone, cetylpyridinium chloride, propolis and eugenol. Of the two gels that were non-cytotoxic, Syntoss Biogel (containing chondrontin sulfate) and Emdogain (EMD, containing amelogenin and propylene glycol alginate), EMD showed the best wound closure, with no effect on P. gingivalis growth but decreased gingipain activity. On the other hand, Syntoss Biogel reduced viability and gingipain activity of P. gingivalis, but lack wound healing capacity. In the 3D GTE, Syntoss Biogel and EMD showed a good biocompatibility. Among all the tested gels, formulations containing CHX, asiaticoside, enoxolone, cetylpyridinium chloride, propolis and eugenol showed high antibacterial effect but also showed high cytotoxicity in eukaryotic cells. EMD was the one with the best biocompatibility and wound healing ability at the conditions tested.
Graphene Oxide and Graphene Quantum Dots as Delivery Systems of Cationic Porphyrins: Photo-Antiproliferative Activity Evaluation towards T24 Human Bladder Cancer Cells
Authors: Menilli Luca , Monteiro Ana R. , Lazzarotto Silvia , Morais Filipe M. P. , Gomes Ana T. P. C. , Moura Nuno M. M. , Fateixa Sara , Faustino Maria A. F. , Neves Maria G. P. M. S. , Trindade Tito , Miolo Giorgia
Published: September 2021

The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C5) were non-covalently loaded onto graphene oxide (GO) or graphene quantum dots (GQDs) in a one-step process. The cytotoxic effects of the free PS and of the corresponding hybrids were compared upon blue (BL) and red-light (RL) exposure on T24 human BC cells. In addition, intracellular reactive oxygen species (ROS) and singlet oxygen generation were measured. TMPyP and Zn-TMPyP showed higher efficiency under BL (IC50: 0.42 and 0.22 μm, respectively), while P1-C5 was more active under RL (IC50: 0.14 μm). In general, these PS could induce apoptotic cell death through lysosomes damage. The in vitro photosensitizing activity of the PS was not compromised after their immobilization onto graphene-based nanomaterials, with Zn-TMPyP@GQDs being the most promising hybrid system under RL (IC50: 0.37 μg/mL). Overall, our data confirm that GO and GQDs may represent valid platforms for PS delivery, without altering their performance for PDT on BC cells.
Functionalized Dendrimer Platforms as a New Forefront Arsenal Targeting SARS-CoV-2: An Opportunity
Authors: Mignani Serge , Shi Xiangyang , Karpus Andrii , Lentini Giovanni , Majoral Jean-Pierre
Published: September 2021

The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official name for the coronavirus disease) pandemic. as the FDA (U.S. Food and Drug Administration) approved antiviral drugs and anti-inflammatory drugs to arrest the cytokine storm, inducing the production of pro-inflammatory cytokines. Another view to solve these unprecedented challenges is to analyze the diverse nanotechnological approaches which are able to improve the COVID-19 pandemic. In this original minireview, as promising candidates we analyze the opportunity to develop biocompatible dendrimers as drugs themselves or as nanocarriers against COVID-19 disease. From the standpoint of COVID-19, we suggest developing dendrimers as shields against COVID-19 infection based on their capacity to be incorporated in several environments outside the patients and as important means to stop transmission of SARS-CoV-2.
Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities
Authors: Xiang Yong , Wong Kenneth Chi-Yin , So Hon-Cheong
Published: September 2021

Effective therapies for COVID-19 are still lacking, and drug repositioning is a promising approach to address this problem. Here, we adopted a medical informatics approach to repositioning. We leveraged a large prospective cohort, the UK-Biobank (UKBB, N ~ 397,000), and studied associations of prior use of all level-4 ATC drug categories (N = 819, including vaccines) with COVID-19 diagnosis and severity. Effects of drugs on the risk of infection, disease severity, and mortality were investigated separately. Logistic regression was conducted, controlling for main confounders. We observed strong and highly consistent protective associations with statins. Many top-listed protective drugs were also cardiovascular medications, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blocker (CCB), and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones, proton pump inhibitors, and testosterone-5-alpha reductase inhibitors, among others. We also observed protective associations by influenza, pneumococcal, and several other vaccines. Subgroup and interaction analyses were also conducted, which revealed differences in protective effects in various subgroups. For example, protective effects of flu/pneumococcal vaccines were weaker in obese individuals, while protection by statins was stronger in cardiovascular patients. To conclude, our analysis revealed many drug repositioning candidates, for example several cardiovascular medications. Further studies are required for validation.
Cellulose Nanofibers Improve the Performance of Retrograded Starch/Pectin Microparticles for Colon-Specific Delivery of 5-ASA
Authors: Meneguin Andréia Bagliotti , Sábio Rafael Miguel , de Souza Maurício Palmeira Chaves , Fernandes Richard Perosa , de Oliveira Anselmo Gomes , Chorilli Marlus
Published: September 2021

Cellulose nanofibers (CNF) were employed as the nanoreinforcement of a retrograded starch/pectin (RS/P) excipient to optimize its colon-specific properties. Although starch retrogradation ranged from 32 to 73%, CNF addition discretely disfavored the RS yield. This result agrees with the finding that in situ CNF reduces the presence of the RS crystallinity pattern. A thermal analysis revealed that the contribution of pectin improves the thermal stability of the RS/CNF mixture. Through a complete factorial design, it was possible to optimize the spray-drying conditions to obtain powders with high yield (57%) and low moisture content (1.2%). The powders observed by Field Emission Gum Scanning Electron Microscopy (FEG-SEM) had 1–10 µm and a circular shape. The developed methodology allowed us to obtain 5-aminosalicilic acid-loaded microparticles with high encapsulation efficiency (16–98%) and drug loading (1.97–26.63%). The presence of CNF in RS/P samples was responsible for decreasing the burst effect of release in simulated gastric and duodenal media, allowing the greatest mass of drug to be targeted to the colon. Considering that spray-drying is a scalable process, widely used by the pharmaceutical industry, the results obtained indicate the potential of these microparticles as raw material for obtaining other dosage forms to deliver 5-ASA to the distal parts of gastrointestinal tract, affected by inflammatory bowel disease.
Synthesis and Biochemical Evaluation of Baicalein Prodrugs
Authors: Son Sang-Hyun , Kang Jinhong , Ahn Myunghwan , Nam Soyeon , Jung Yong Woo , Lee Ki Yong , Jeon Young Ho , Byun Youngjoo , Lee Kiho
Published: September 2021

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs.
Mesoporous Calcium-Silicate Nanoparticles Loaded with Low-Dose Triton-100+Ag+ to Achieve Both Enhanced Antibacterial Properties and Low Cytotoxicity for Dentin Disinfection of Human Teeth
Authors: Duan Mengting , Fan Wei , Fan Bing
Published: September 2021

Mesoporous calcium-silicate nanoparticles (MCSNs) are excellent biomaterials for controlled drug delivery and mineralization induction. In this study, MCSNs were loaded with low-dose silver ion (Ag+) and Triton X-100 (TX-100) as the M-AgTX to achieve both enhanced antibacterial properties and low cytotoxicity for dentin disinfection. The physicochemical property, biocompatibility, infiltration ability into dentinal tubules, anti-bacterial ability against both planktonic Enterococcusfaecalis (E. faecalis) and its biofilm on dentin, effects on dentin microhardness and in vitro mineralization property were systematically investigated. Results confirmed that the MCSNs and M-AgTX nanoparticles showed typical morphology of mesoporous materials and exhibited sustained release of chemicals with an alkaline pH value over time. M-AgTX also exhibited excellent biocompatibility on MC3T3-E1 cells and could eliminate 100% planktonic E. faecalis after 48-h treatment. On dentin slices, it could enter dentinal tubules by ultrasonic activation and inhibit the growth of E. faecalis on dentin. M-AgTX could completely inactive 28-day E. faecalis biofilm. TEM confirmed the destruction of cell membrane integrity and Ag+ infiltration into bacteria by M-AgTX. Besides, dentin slices medicated with M-AgTX nanoparticles displayed an increased microhardness. After being immersed in SBF for 7 days, apatite crystals could be observed on the surface of the material tablets. M-AgTX could be developed into a new multifunctional intra-canal medication or bone defect filling material for infected bone defects due to its sustained release profile, low cytotoxicity, infiltration ability, enhanced anti-bacterial and mineralization features.
Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation
Authors: Wang Jieting , Yu Luying , Zhou Ao , Liu Jie , Wang Kai , Luo Ying , Wang Fang
Published: September 2021

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.
3D Printing of Thermo-Sensitive Drugs
Authors: Abdella Sadikalmahdi , Youssef Souha H. , Afinjuomo Franklin , Song Yunmei , Fouladian Paris , Upton Richard , Garg Sanjay
Published: September 2021

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.
Multifunctional Nanofibrous Dressing with Antimicrobial and Anti-Inflammatory Properties Prepared by Needle-Free Electrospinning
Authors: Schulte-Werning Laura Victoria , Murugaiah Anjanah , Singh Bhupender , Johannessen Mona , Engstad Rolf Einar , Škalko-Basnet Nataša , Holsæter Ann Mari
Published: September 2021

An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and CHI are active nanofiber-forming biopolymers isolated from the cell walls of Saccharomyces cerevisiae and from shrimp shells, respectively. To evaluate the effect of each active ingredient on the nanofibers’ morphological features and bioactivity, nanofibers with both βG and CHI, only βG, only CHI and only copolymers, polyethylene oxide (PEO) and hydroxypropylmethylcellulose (HPMC) were fabricated. All four nanofiber formulations were also prepared with 1% CAM. The needle-free NanospiderTM technique allowed for the successful production of defect-free nanofibers containing all three active ingredients. The CAM-containing nanofibers had a burst CAM-release and a high absorption capacity. Nanofibers with all active ingredients (βG, CHI and CAM) showed a concentration-dependent anti-inflammatory activity, while maintaining the antimicrobial activity of CAM. The promising anti-inflammatory properties, together with the high absorption capacity and antimicrobial effect, make these multifunctional nanofibers promising as dressings in local treatment of infected and exuding wounds, such as burn wounds.
A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy
Authors: Barbălată Cristina Ioana , Porfire Alina Silvia , Sesarman Alina , Rauca Valentin-Florian , Banciu Manuela , Muntean Dana , Știufiuc Rareș , Moldovan Alin , Moldovan Cristian , Tomuță Ioan
Published: September 2021

An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.
Characterization of Collagen I Fiber Thickness, Density, and Orientation in the Human Skin In Vivo Using Second-Harmonic Generation Imaging
Authors: Kröger Marius , Schleusener Johannes , Jung Sora , Darvin Maxim E.
Published: September 2021

The assessment of dermal alterations is necessary to monitor skin aging, cancer, and other skin diseases and alterations. The gold standard of morphologic diagnostics is still histopathology. Here, we proposed parameters to distinguish morphologically different collagen I structures in the extracellular matrix and to characterize varying collagen I structures in the skin with similar SAAID (SHG-to-AF Aging Index of Dermis, SHG—second-harmonic generation; AF—autofluorescence) values. Test datasets for the papillary and reticular extracellular matrix from images in 24 female subjects, 36 to 50 years of age, were generated. Parameters for SAAID, edge detection, and fast Fourier transformation directionality were determined. Additionally, textural analyses based on the grey level co-occurrence matrix (GLCM) were conducted. At first, changes in the GLCM parameters were determined in the native greyscale images and, furthermore, in the Hilbert-transformed images. Our results demonstrate a robust set of parameters for noninvasive in vivo classification for morphologically different collagen I structures in the skin, with similar and different SAAID values. We anticipate our method to enable an automated prevention and monitoring system with an age- and gender-specific algorithm.
Tree Growth Conditions Are Demanded When Optimal, Are Unwanted When Limited, but When Are They Suboptimal?
Authors: Cocozza Claudia , Traversi Maria Laura , Giovannelli Alessio
Published: September 2021

The recent climate projections predict that the intensity and frequency of extreme events will increase as a result of overall increasing mean temperature and reduced precipitations in the temperate regions of the Northern Hemisphere. How these changes will influence the harshness of the environment and the performances of trees growing under natural conditions remains an open question. In this commentary article, we would like to look at the concept of suboptimal growth conditions, widening its application from the traditional in vitro manipulation to trees growing in open air, addressing the main limitations and strengths of the upscaling results from cell to tree. We believe that the traditional single dose–effect approach is not suitable to explain the complex interactions between genotype and environment, occurring in open field or forest stands, where the intensity and frequency of the events are uncontrolled and unpredictable. As forests provide a wide range of ecosystem services, new parameters should be considered in the definition of the response thresholds in addition to growth. Thus, within this Special Issue, we stimulate the discussion over the development of new approaches and technologies that are able to define suitable threshold responses of trees under suboptimal natural conditions, with the aim to furnish new insights on the acclimation and adaptation processes in woody species under global change.
The Impact of Different Types of Hydrocarbon Disturbance on the Resiliency of Native Desert Vegetation in a War-Affected Area: A Case Study from the State of Kuwait
Authors: Kalander Eman , Abdullah Meshal M. , Al-Bakri Jawad
Published: September 2021

This study assesses the impact of total petroleum hydrocarbon (TPH) concentration and soil parameters (heavy metals, chemical properties, and water-soluble boron) on the succession process of vegetation survival in the Al-Burgan oil field in Kuwait. A total of 145 soil samples were randomly collected from the three main types of hydrocarbon contamination, including dry oil lake (DOL), wet oil lake (WOL), and tarcrete. Sampling was also extended to noncontaminated bare soils that were considered reference sites. Remote-sensing data from Sentinel-2 were also processed to assess the level of contamination in relation to soil surface cover. The results showed that TPH concentration was significantly higher in WOL and DOL (87,961.4 and 35,740.6 mg/kg, respectively) compared with that in tarcrete (24,063.3 mg/kg), leading to a significant increase in soil minerals and heavy metals, greater than 50 mg/kg for Ba, and 10 mg/kg for V, Zn, Ni, and Cr. Such high concentrations of heavy metals massively affected the native vegetation’s resiliency at these sites (<5% vegetation cover). However, vegetation cover was significantly higher (60%) at tarcrete-contaminated sites, as TPH concentration was lower, almost similar to that in uncontaminated areas, especially at subsurface soil layers. The presence of vegetation at tarcrete locations was also associated with the lower concentration of Ba, V, Zn, Ni, and Cr. The growth of native vegetation was more likely related to the low concentration of TPH contamination at the subsurface layer of the soils in tarcrete sites, making them more suitable sites for restoration and revegetation planning. We concluded that further investigations are required to provide greater insight into the native plants’ phytoextraction potential and phytoremediation.
The Effect of Water Deficit on Two Greek Vitis vinifera L. Cultivars: Physiology, Grape Composition and Gene Expression during Berry Development
Authors: Alatzas Anastasios , Theocharis Serafeim , Miliordos Dimitrios-Evangelos , Leontaridou Konstantina , Kanellis Angelos K. , Kotseridis Yorgos , Hatzopoulos Polydefkis , Koundouras Stefanos
Published: September 2021

Plants are exposed to numerous abiotic stresses. Drought is probably the most important of them and determines crop distribution around the world. Grapevine is considered to be a drought-resilient species, traditionally covering semiarid areas. Moreover, in the case of grapevine, moderate water deficit is known to improve the quality traits of grape berries and subsequently wine composition. However, against the backdrop of climate change, vines are expected to experience sustained water deficits which could be detrimental to both grape quality and yield. The influence of water deficit on two Greek Vitis vinifera L. cultivars, ‘Agiorgitiko’ and ‘Assyrtiko’, was investigated during the 2019 and 2020 vintages. Vine physiology measurements in irrigated and non-irrigated plants were performed at three time-points throughout berry development (green berry, veraison and harvest). Berry growth and composition were examined during ripening. According to the results, water deficit resulted in reduced berry size and increased levels of soluble sugars, total phenols and anthocyanins. The expression profile of specific genes, known to control grape color, aroma and flavor was altered by water availability during maturation in a cultivar-specific manner. In agreement with the increased concentration of phenolic compounds due to water deficit, genes of the phenylpropanoid pathway in the red-skinned Agiorgitiko exhibited higher expression levels and earlier up-regulation than in the white Assyrtiko. The expression profile of the other genes during maturation or in response to water deficit was depended on the vintage.
Genome-Wide Analysis of the IQM Gene Family in Rice (Oryza sativa L.)
Authors: Fan Tian , Lv Tianxiao , Xie Chuping , Zhou Yuping , Tian Changen
Published: September 2021

Members of the IQM (IQ-Motif Containing) gene family are involved in plant growth and developmental processes, biotic and abiotic stress response. To systematically analyze the IQM gene family and their expression profiles under diverse biotic and abiotic stresses, we identified 8 IQM genes in the rice genome. In the current study, the whole genome identification and characterization of OsIQMs, including the gene and protein structure, genome localization, phylogenetic relationship, gene expression and yeast two-hybrid were performed. Eight IQM genes were classified into three subfamilies (I–III) according to the phylogenetic analysis. Gene structure and protein motif analyses showed that these IQM genes are relatively conserved within each subfamily of rice. The 8 OsIQM genes are distributed on seven out of the twelve chromosomes, with three IQM gene pairs involved in segmental duplication events. The evolutionary patterns analysis revealed that the IQM genes underwent a large-scale event within the last 20 to 9 million years. In addition, quantitative real-time PCR analysis of eight OsIQMs genes displayed different expression patterns at different developmental stages and in different tissues as well as showed that most IQM genes were responsive to PEG, NaCl, jasmonic acid (JA), abscisic acid (ABA) treatment, suggesting their crucial roles in biotic, and abiotic stress response. Additionally, a yeast two-hybrid assay showed that OsIQMs can interact with OsCaMs, and the IQ motif of OsIQMs is required for OsIQMs to combine with OsCaMs. Our results will be valuable to further characterize the important biological functions of rice IQM genes.
Androgenesis of Red Cabbage in Isolated Microspore Culture In Vitro
Authors: Mineykina Anna , Bondareva Ludmila , Soldatenko Alexey , Domblides Elena
Published: September 2021

Red cabbage belongs to the economically important group of vegetable crops of the Brassicaceae family. A unique feature of this vegetable crop that distinguishes it from other members of the family is its unique biochemical composition characterized by high anthocyanin content, which gives it antioxidant properties. The production mainly uses F1 hybrids, which require constant parental lines, requiring 6–7 generations of inbreeding. Culture of isolated microspores in vitro is currently one of the promising methods for the accelerated production of pure lines with 100% homozygosity. The aim of this study is to investigate the factors and select optimal parameters for successful induction of red cabbage embryogenesis in isolated microspore culture in vitro and subsequent regeneration of DH plants. As a result of research, for the first time, it was possible to carry out the full cycle of obtaining DH plants of red cabbage from the induction of embryogenesis to their inclusion in the breeding process. The size of buds containing predominantly microspores at the late vacuolated stage and pollen at the early bi-cellular stage has to be selected individually for each genotype, because the embryoid yield will be determined by the interaction of these two factors. In the six samples studied, the maximum embryoid yield was obtained from buds 4.1–4.4 mm and 4.5–5.0 mm long, depending on the genotype. Cultivation of microspores was carried out on liquid NLN culture medium with 13% sucrose. The maximum number of embryoids (173.5 ± 7.5 pcs./Petri dish) was obtained on culture medium with pH 5.8 and heat shock at 32 °C for 48 h. Successful embryoid development and plant regeneration by direct germination from shoot apical meristem were achieved on MS culture medium with 2% sucrose and 0.7% agar, supplemented with 6-benzylaminopurine at a concentration of 1 mg/L. Analysis of the obtained regenerated plants, which successfully passed the stage of adaptation to ex vitro conditions by flow cytometry, showed that most of them were doubled haploids (up to 90.9%). A low number of seeds produced by self-fertilization in DH plants was observed.
Glucosinolate Induction and Resistance to the Cabbage Moth, Mamestra brassicae, Differs among Kale Genotypes with High and Low Content of Sinigrin and Glucobrassicin
Authors: Badenes-Pérez Francisco Rubén , Cartea María Elena
Published: September 2021

The cabbage moth, Mamestra brassicae L. (Lepidoptera: Noctuidae), is a generalist insect pest of cruciferous crops. We tested glucosinolate induction by jasmonic acid (JA) and salicylic acid (SA), and by these phytohormones combined with feeding by M. brassicae larvae in four genotypes of kale, Brassica oleracea L. var. acephala (Brassicaceae). The genotypes tested had high glucobrassicin (genotype HGBS), low glucobrassicin (genotype LGBS), high sinigrin (genotype HSIN), and low sinigrin content (genotype LSIN). Application of JA increased indolic and total glucosinolate content in all kale genotypes 1, 3, and 9 days after treatment. For SA-treated plants, glucosinolate induction varied depending on the number of days after treatment and the genotype. Overall, herbivory by M. brassicae accentuated and attenuated the effects of JA and SA, respectively, on plant glucosinolate content. Larvae of M. brassicae gained less weight on leaves from plants treated with JA compared to leaves from control plants and plants treated with SA. In bioassays with leaf discs, a significant reduction of defoliation only occurred in JA-treated plants of the HSIN genotype. This research shows that previous herbivory alters the susceptibility of kale to M. brassicae and that induction of glucosinolates varies among kale genotypes differing in their glucosinolate content.
Ecological and Biological Properties of Satureja cuneifolia Ten. and Thymus spinulosus Ten.: Two Wild Officinal Species of Conservation Concern in Apulia (Italy). A Preliminary Survey
Authors: Perrino Enrico V. , Valerio Francesca , Jallali Shaima , Trani Antonio , Mezzapesa Giuseppe N.
Published: September 2021

This study evaluated the effects of ecology (plant community, topography and pedology), as well as of climate, on the composition of essential oils (EOs) from two officinal wild plant species (Lamiales) from Apulia, namely Satureja cuneifolia Ten. and Thymus spinulosus Ten. Few scientific data on their chemical composition are available, due to the fact that the first has a limited distribution range and the second is endemic of southern Italy. Results for both species, never officially used in traditional medicine and/or as spices, showed that the ecological context (from a phytosociological and ecological point of view) may influence their EO composition, and hence, yield chemotypes different from those reported in the literature. S. cuneifolia and Th. spinulosus can be considered good sources of phytochemicals as natural agents in organic agriculture due to the presence of thymol and α-pinene. Overall, the obtained trend for EOs suggests a potential use of both species as food, pharmacy, cosmetics and perfumery. Hence, their cultivation and use represent a positive step to reduce the use of synthetic chemicals and to meet the increasing demand for natural and healthier products.
Morphology, Anatomy and Secondary Metabolites Investigations of Premna odorata Blanco and Evaluation of Its Anti-Tuberculosis Activity Using In Vitro and In Silico Studies
Authors: Youssef Fadia S. , Ovidi Elisa , Musayeib Nawal M. Al , Ashour Mohamed L.
Published: September 2021

In-depth botanical characterization was performed on Premna odorata Blanco (Lamiaceae) different organs for the first time. The leaves are opposite, hairy and green in color. Flowers possess fragrant aromatic odors and exist in inflorescences of 4–15 cm long corymbose cyme-type. In-depth morphological and anatomical characterization revealed the great resemblance to plants of the genus Premna and of the family Lamiaceae, such as the presence of glandular peltate trichomes and diacytic stomata. Additionally, most examined organs are characterized by non-glandular multicellular covering trichomes, acicular, and rhombic calcium oxalate crystals. P. odorata leaves n-hexane fraction revealed substantial anti-tuberculous potential versus Mycobacterium tuberculosis, showing a minimum inhibition concentration (MIC) of 100 μg/mL. Metabolic profiling of the n-hexane fraction using gas-chromatography coupled to mass spectrometry (GC/MS) analysis revealed 10 major compounds accounting for 93.01%, with trans-phytol constituting the major compound (24.06%). The virtual screening revealed that trans-phytol highly inhibited MTB C171Q receptor as M. tuberculosis KasA (β-ketoacyl synthases) with a high fitting score (∆G = −15.57 kcal/mol) approaching that of isoniazid and exceeding that of thiolactomycin, the co-crystallized ligand. Absorption, distribution, metabolism, excretion and toxicity predictions (ADME/TOPKAT) revealed that trans-phytol shows lower solubility and absorption levels when compared to thiolactomycin and isoniazid. Still, it is safer, causing no mutagenic or carcinogenic effects with higher lethal dose, which causes the death of 50% (LD50). Thus, it can be concluded that P. odorata can act as a source of lead entities to treat tuberculosis.
Diversity and Cytogenomic Characterization of Wild Carrots in the Macaronesian Islands
Authors: Roxo Guilherme , Moura Mónica , Talhinhas Pedro , Costa José Carlos , Silva Luís , Vasconcelos Raquel , de Sequeira Miguel Menezes , Romeiras Maria Manuel
Published: September 2021

The Macaronesian islands constitute an enormous reservoir of genetic variation of wild carrots (subtribe Daucinae; Apiaceae), including 10 endemic species, but an accurate understanding of the diversification processes within these islands is still lacking. We conducted a review of the morphology, ecology, and conservation status of the Daucinae species and, on the basis of a comprehensive dataset, we estimated the genome size variation for 16 taxa (around 320 samples) occurring in different habitats across the Macaronesian islands in comparison to mainland specimens. Results showed that taxa with larger genomes (e.g., Daucus crinitus: 2.544 pg) were generally found in mainland regions, while the insular endemic taxa from Azores and Cabo Verde have smaller genomes. Melanoselinum decipiens and Monizia edulis, both endemic to Madeira Island, showed intermediate values. Positive correlations were found between mean genome size and some morphological traits (e.g., spiny or winged fruits) and also with habit (herbaceous or woody). Despite the great morphological variation found within the Cabo Verde endemic species, the 2C-values obtained were quite homogeneous between these taxa and the subspecies of Daucus carota, supporting the close relationship among these taxa. Overall, this study improved the global knowledge of DNA content for Macaronesian endemics and shed light into the mechanisms underpinning diversity patterns of wild carrots in the western Mediterranean region.
Chemical Composition, Anti-Quorum Sensing, Enzyme Inhibitory, and Antioxidant Properties of Phenolic Extracts of Clinopodium nepeta L. Kuntze
Authors: Beddiar Hatem , Boudiba Sameh , Benahmed Merzoug , Tamfu Alfred Ngenge , Ceylan Özgür , Hanini Karima , Kucukaydin Selcuk , Elomri Abdelhakim , Bensouici Chawki , Laouer Hocine , Akkal Salah , Boudiba Louiza , Dinica Rodica Mihaela
Published: September 2021

Phenolic extracts of Clinopodium nepeta were prepared and their preliminary phenolic profiles determined using HPLC-DAD with 26 phenolic standards. Apigenin (21.75 ± 0.41 µg/g), myricetin (72.58 ± 0.57 µg/g), and rosmarinic acid (88.51 ± 0.55 µg/g) were the most abundant compounds in DCM (dichloromethane), AcOEt (ethyl acetate), and BuOH (butanol) extracts, respectively. The DCM and AcOEt extracts inhibited quorum-sensing mediated violacein production by C. violaceum CV12472. Anti-quorum-sensing zones on C. violaceum CV026 at MIC (minimal inhibitory concentration) were 10.3 ± 0.8 mm for DCM extract and 12.0 ± 0.5 mm for AcOEt extract. Extracts showed concentration-dependent inhibition of swarming motility on flagellated P. aeruginosa PA01 and at the highest test concentration of 100 μg/mL, AcOEt (35.42 ± 1.00%) extract displayed the best activity. FRAP assay indicated that the BuOH extract (A0.50 = 17.42 ± 0.25 µg/mL) was more active than standard α-tocopherol (A0.50 = 34.93 ± 2.38 µg/mL). BuOH extract was more active than other extracts except in the ABTS●+, where the DCM extract was most active. This antioxidant activity could be attributed to the phenolic compounds detected. C. nepeta extracts showed moderate inhibition on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, and α-amylase. The results indicate that C. nepeta is a potent source of natural antioxidants that could be used in managing microbial resistance and Alzheimer′s disease.
Molecular and Enzymatic Characterization of Flavonoid 3′-Hydroxylase of Malus × domestica
Authors: Weissensteiner Julia , Molitor Christian , Marinovic Silvija , Führer Lisa , Waqas Hassan Syed , Hutabarat Olly Sanny , Spornberger Andreas , Stich Karl , Hausjell Johanna , Spadiut Oliver , Haselmair-Gosch Christian , Halbwirth Heidi
Published: September 2021

Malus × domestica (apple) accumulates particularly high amounts of dihydrochalcones in various tissues, with phloridzin (phloretin 2′-O-glucoside) being prevalent, although small amounts of 3-hydroxyphloretin and 3-hydroxyphloridzin are also constitutively present. The latter was shown to correlate with increased disease resistance of transgenic M. × domestica plants. Two types of enzymes could be involved in 3-hydroxylation of dihydrochalcones: polyphenol oxidases or the flavonoid 3′-hydroxylase (F3′H), which catalyzes B-ring hydroxylation of flavonoids. We isolated two F3′H cDNA clones from apple leaves and tested recombinant Malus F3′Hs for their substrate specificity. From the two isolated cDNA clones, only F3′HII encoded a functionally active enzyme. In the F3′HI sequence, we identified two putatively relevant amino acids that were exchanged in comparison to that of a previously published F3′HI. Site directed mutagenesis, which exchanged an isoleucine into methionine in position 211 restored the functional activity, which is probably because it is located in an area involved in interaction with the substrate. In contrast to high activity with various flavonoid substrates, the recombinant enzymes did not accept phloretin under assay conditions, making an involvement in the dihydrochalcone biosynthesis unlikely.
Antioxidant Activity and Discrimination of Organic Apples (Malus domestica Borkh.) Cultivated in the Western Region of Romania: A DPPH· Kinetics–PCA Approach
Authors: Iordănescu Olimpia Alina , Băla Maria , Iuga Alina Carmen , Gligor (Pane) Dina , Dascălu Ionuţ , Bujancă Gabriel Stelian , David Ioan , Hădărugă Nicoleta Gabriela , Hădărugă Daniel Ioan
Published: September 2021

Apple (Malus domestica Borkh.) is one of the most used fruit for beverages in Romania. The goal of the study was to evaluate the antioxidant activity and discrimination of various parts of organic and non-organic apple varieties cultivated in the western region of Romania using the DPPH kinetics–PCA (principal component analysis) approach. Organic and non-organic apples were subjected to solid–liquid ethanol extraction. Core and shell extracts were mixed with DPPH· and spectrophotometrically monitored at 517 nm. Antioxidant activity and mean DPPH· reaction rate at various time ranges reveal significant differences between organic and non-organic samples, as well as apple parts. Organic core and shell extracts had higher antioxidant activities than the corresponding non-organic samples (74.5–96.9% and 61.9–97.2%, respectively, 23.5–94.3% and 59.5–95.5%). Significant differences were observed for the DPPH· reaction rate for the first ½ min, especially in the presence of organic core extracts (3.7–4.8 μM/s). The organic samples were well discriminated by DPPH· kinetics–PCA, the most important variables being the DPPH· reaction rate for the first time range. This is the first DPPH· kinetics–PCA approach applied for discriminating between organic and non-organic fruits and can be useful for evaluating the quality of such type of fruits.