bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Synthesis of the Amino Lipid ECO for Effective Delivery of Nucleic Acids
Authors: Schilb Andrew L. , Scheidt Josef H. , Vaidya Amita M. , Sun Zhanhu , Sun Da , Lee Sangjoon , Lu Zheng-Rong
Published: October 2021

Nucleic acids are promising for a variety of therapies, such as cancer therapy and the gene therapy of genetic disorders. The therapeutic efficacy of nucleic acids is reliant on the ability of their efficient delivery to the cytosol of the target cells. Amino lipids have been developed to aid in the cytosolic delivery of nucleic acids. This work reports a new and efficient synthetic pathway for the lipid carrier, (1-aminoethyl) iminobis [N-(oleicylcysteinyl-1-amino-ethyl)propionamide] (ECO). The previous synthesis of the ECO was inefficient and presented poor product quality control. A solution-phase synthesis of the ECO was explored, and each intermediate product was characterized with better quality control. The ECO was synthesized with a relatively high yield and high purity. The formulations of the ECO nanoparticles were made with siRNA, miRNA, or plasmid DNA, and characterized. The transfection efficiency of the nanoparticles was evaluated in vitro over a range of N/P ratios. The nanoparticles were consistent in size with previous formulations and had primarily a positive zeta potential. The ECO/siLuc nanoparticles resulted in potent luciferase silencing with minimal cytotoxicity. The ECO/miR-200c nanoparticles mediated the efficient delivery of miR-200c into the target cells. The ECO/pCMV-GFP nanoparticles resulted in substantial GFP expression upon transfection. These results demonstrate that the solution-phase synthetic pathway produced pure ECO for the efficient intracellular delivery of nucleic acids without size limitation.
Comparison of Ethanolic and Aqueous Populus balsamifera L. Bud Extracts by Different Extraction Methods: Chemical Composition, Antioxidant and Antibacterial Activities
Authors: Stanciauskaite Monika , Marksa Mindaugas , Babickaite Lina , Majiene Daiva , Ramanauskiene Kristina
Published: October 2021

The balsam poplar (Populus balsamifera L.) buds that grow in Lithuania are a polyphenol-rich plant material with a chemical composition close to that of propolis. In order to potentially adapt the extracts of this plant’s raw material for therapeutic purposes, it is important to carry out detailed studies on the chemical composition and biological activity of balsam poplar buds. An important step is to evaluate the yield of polyphenols by different extraction methods and using different solvents. According to our research, extracts of balsam poplar buds collected in Lithuania are dominated by p-coumaric (496.9–13,291.2 µg/g), cinnamic acid (32.9–11,788.5 µg/g), pinobanksin (34.9–1775.5 µg/g) and salicin (215.3–1190.7 µg/g). The antioxidant activity of poplar buds was evaluated by the ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric-reducing antioxidant power) methods, all extracts showed antioxidant activity and the obtained results correlated with the obtained amounts of total phenolic compounds in the extracts (ABTS r = 0.974; DPPH r = 0.986; FRAP r = 0.955, p < 0.01). Studies of antimicrobial activity have shown that ethanolic extracts have an antimicrobal activity effect against Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. The extracts showed a better antimicrobal activity against gram-positive bacteria.
Anti-Proliferative, Anti-Angiogenic and Safety Profiles of Novel HDAC Inhibitors for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Rana Zohaib , Diermeier Sarah , Walsh Fearghal P. , Hanif Muhammad , Hartinger Christian G. , Rosengren Rhonda J.
Published: October 2021

Metastatic castration-resistant prostate cancer (CRPC) has a five-year survival rate of 28%. As histone deacetylases (HDACs) are overexpressed in CRPC, the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was trialled in CRPC patients but found to be toxic and inefficacious. Previously, we showed that novel HDAC inhibitors (Jazz90 (N1-hydroxy-N8-(4-(pyridine-2-carbothioamido)phenyl)octanediamide) and Jazz167 ([chlorido(η5-pentamethylcyclopentadieny[1–4](N1-hydroxy-N8-(4-(pyridine-2-carbothioamido-κ2N,S)phenyl)octanediamide)rhodium(III)] chloride) had a higher cancer-to-normal-cell selectivity and superior anti-angiogenic effects in CRPC (PC3) cells than SAHA. Thus, this study aimed to further investigate the efficacy and toxicity of these compounds. HUVEC tube formation assays revealed that Jazz90 and Jazz167 significantly reduced meshes and segment lengths in the range of 55–88 and 43–64%, respectively. However, Jazz90 and Jazz167 did not affect the expression of epithelial-to-mesenchymal transitioning markers E-cadherin and vimentin. Jazz90 and Jazz167 significantly inhibited the growth of PC3 and DU145 spheroids and reduced PC3 spheroid branching. Jazz90 and Jazz167 (25, 50 and 75 mg/kg/day orally for 21 days) were non-toxic in male BALB/c mice. The efficacy and safety of these compounds demonstrate their potential for further in vivo studies in CRPC models.
Multilayer Films Based on Chitosan/Pectin Polyelectrolyte Complexes as Novel Platforms for Buccal Administration of Clotrimazole
Authors: Potaś Joanna , Szymańska Emilia , Wróblewska Magdalena , Kurowska Izabela , Maciejczyk Mateusz , Basa Anna , Wolska Eliza , Wilczewska Agnieszka Zofia , Winnicka Katarzyna
Published: October 2021

Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa intended for the therapy of oromucosal conditions, especially infectious diseases. Multilayer films composed of layers of oppositely charged polymers separated by ionically interacting polymeric chains creating polyelectrolyte complexes represent very interesting and relatively poorly explored area. We aimed to develop the antifungal multilayer systems composed of cationic chitosan and anionic pectin as potential platforms for controlled delivery of clotrimazole. The systems were pharmaceutically characterized with regard to inter alia their release kinetics under different pH conditions, physicomechanical, or mucoadhesion properties with using an animal model of the buccal mucosa. The antifungal activity against selected Candida sp. and potential cytotoxicity with regard to human gingival fibroblasts were also evaluated. Interactions between polyions were characterized with Fourier transform infrared spectroscopy. Different clotrimazole distribution in the films layers highly affected their in vitro dissolution profile. The designed films were recognized as intelligent pH-responsive systems with strong antifungal effect and satisfactory safety profile. As addition of chitosan resulted in the improved antifungal behavior of the drug, the potential utilization of the films in resistant cases of oral candidiasis might be worth of further exploration.
Novel Nanocombinations of l-Tryptophan and l-Cysteine: Preparation, Characterization, and Their Applications for Antimicrobial and Anticancer Activities
Authors: Abd-Elhamid Ahmed I. , El-Gendi Hamada , Abdallah Abdallah E. , El-Fakharany Esmail M.
Published: October 2021

Tungsten oxide WO3 nanoparticles (NPs) were prepared in a form of nanosheets with homogeneous size and dimensions in one step through acid precipitation using a cation exchange column. The resulting WO3 nanosheet surface was decorated with one of the two amino acids (AAs) l-tryptophan (Trp) or l-cysteine (Cys) and evaluated for their dye removal, antimicrobial, and antitumor activities. A noticeable improvement in the biological activity of WO3 NPs was detected upon amino acid modification compared to the original WO3. The prepared WO3-Trp and WO3-Cys exhibited strong dye removal activity toward methylene blue and safranin dyes with complete dye removal (100%) after 6 h. WO3-Cys and WO3-Trp NPs revealed higher broad-spectrum antibacterial activity toward both Gram-negative and Gram-positive bacteria, with strong antifungal activity toward Candida albicans. Anticancer results of the modified WO3-Cys and WO3-Trp NPs against various kinds of cancer cells, including MCF-7, Caco-2, and HepG-2 cells, indicate that they have a potent effect in a dose-dependent manner with high selectivity to cancer cells and safety against normal cells. The expression levels of E2F2 and Bcl-2 genes were found to be suppressed after treatment with both WO3-Cys and WO3-Trp NPs more than 5-FU-treated cells. While expression level of the p53 gene in all tested cells was up-regulated after treatment 5–8 folds more as compared to untreated cells. The docking results confirmed the ability of both NPs to bind to the p53 gene with relevant potency in binding to other tested gens and participation of cysteine SH-functional group in such interaction.
Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics
Authors: Huang Huanshao , Wang Jiajun , Zhang Junai , Cai Jiye , Pi Jiang , Xu Jun-Fa
Published: October 2021

Cobalt is essential to the metabolism of all animals due to its key role in cobalamin, also known as vitamin B12, the primary biological reservoir of cobalt as an ultra-trace element. Current cancer treatment strategies, including chemotherapy and radiotherapy, have been seriously restricted by their side effects and low efficiency for a long time, which urges us to develop new technologies for more effective and much safer anticancer therapies. Novel nanotechnologies, based on different kinds of functional nanomaterials, have been proved to act as effective and promising strategies for anticancer treatment. Based on the important biological roles of cobalt, cobalt oxide nanoparticles (NPs) have been widely developed for their attractive biomedical applications, especially their potential for anticancer treatments due to their selective inhibition of cancer cells. Thus, more and more attention has been attracted to the preparation, characterization and anticancer investigation of cobalt oxide nanoparticles in recent years, which is expected to introduce novel anticancer treatment strategies. In this review, we summarize the synthesis methods of cobalt oxide nanoparticles to discuss the advantages and restrictions for their preparation. Moreover, we emphatically discuss the anticancer functions of cobalt oxide nanoparticles as well as their underlying mechanisms to promote the development of cobalt oxide nanoparticles for anticancer treatments, which might finally benefit the current anticancer therapeutics based on functional cobalt oxide nanoparticles.
Effective Degradation of Gluten and Its Fragments by Gluten-Specific Peptidases: A Review on Application for the Treatment of Patients with Gluten Sensitivity
Authors: Dunaevsky Yakov E. , Tereshchenkova Valeriia F. , Belozersky Mikhail A. , Filippova Irina Y. , Oppert Brenda , Elpidina Elena N.
Published: October 2021

To date, there is no effective treatment for celiac disease (CD, gluten enteropathy), an autoimmune disease caused by gluten-containing food. Celiac patients are supported by a strict gluten-free diet (GFD). However, in some cases GFD does not negate gluten-induced symptoms. Many patients with CD, despite following such a diet, retain symptoms of active disease due to high sensitivity even to traces of gluten. In addition, strict adherence to GFD reduces the quality of life of patients, as often it is difficult to maintain in a professional or social environment. Various pharmacological treatments are being developed to complement GFD. One promising treatment is enzyme therapy, involving the intake of peptidases with food to digest immunogenic gluten peptides that are resistant to hydrolysis due to a high prevalence of proline and glutamine amino acids. This narrative review considers the features of the main proline/glutamine-rich proteins of cereals and the conditions that cause the symptoms of CD. In addition, we evaluate information about peptidases from various sources that can effectively break down these proteins and their immunogenic peptides, and analyze data on their activity and preliminary clinical trials. Thus far, the data suggest that enzyme therapy alone is not sufficient for the treatment of CD but can be used as a pharmacological supplement to GFD.
Impact of Drug Loading Method on Drug Release from 3D-Printed Tablets Made from Filaments Fabricated by Hot-Melt Extrusion and Impregnation Processes
Authors: Thanawuth Kasitpong , Sutthapitaksakul Lalinthip , Konthong Srisuda , Suttiruengwong Supakij , Huanbutta Kampanart , Dass Crispin R. , Sriamornsak Pornsak
Published: October 2021

The purpose of this study was to investigate the impact of the drug loading method on drug release from 3D-printed tablets. Filaments comprising a poorly water-soluble model drug, indomethacin (IND), and a polymer, polyvinyl alcohol (PVA), were prepared by hot-melt extrusion (HME) and compared with IND-loaded filaments prepared with an impregnation (IMP) process. The 3D-printed tablets were fabricated using a fused deposition modeling 3D printer. The filaments and 3D printed tablets were evaluated for their physicochemical properties, swelling and matrix erosion behaviors, drug content, and drug release. Physicochemical investigations revealed no drug–excipient interaction or degradation. IND-loaded PVA filaments produced by IMP had a low drug content and a rapid drug release. Filaments produced by HME with a lower drug content released the drug faster than those with a higher drug content. The drug content and drug release of 3D-printed tablets containing IND were similar to those of the filament results. Particularly, drug release was faster in 3D-printed tablets produced with filaments with lower drug content (both by IMP and HME). The drug release of 3D-printed tablets produced from HME filaments with higher drug content was extended to 24 h due to a swelling-erosion process. This study confirmed that the drug loading method has a substantial influence on drug content, which in turn has a significant effect on drug release. The results suggest that increasing the drug content in filaments might delay drug release from 3D-printed tablets, which may be used for developing dosage forms suited for personalized medicine.
Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation
Authors: González-Ruiz Víctor , Cores Ángel , Martín-Cámara Olmo , Orellana Karen , Cervera-Carrascón Víctor , Michalska Patrycja , Olives Ana I. , León Rafael , Martín M. Antonia , Menéndez J. Carlos
Published: October 2021

The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.
Can the Nasal Cavity Help Tackle COVID-19?
Authors: Pilicheva Bissera , Boyuklieva Radka
Published: October 2021

Despite the progress made in the fight against the COVID-19 pandemic, it still poses dramatic challenges for scientists around the world. Various approaches are applied, including repurposed medications and alternative routes for administration. Several vaccines have been approved, and many more are under clinical and preclinical investigation. This review aims to systemize the available information and to outline the key therapeutic strategies for COVID-19, based on the nasal route of administration.
Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape
Authors: Battaglia Luigi , Scomparin Anna , Dianzani Chiara , Milla Paola , Muntoni Elisabetta , Arpicco Silvia , Cavalli Roberta
Published: October 2021

Cutaneous melanoma is one of the most aggressive solid tumors, with a low survival for the metastatic stage. Currently, clinical melanoma treatments include surgery, chemotherapy, targeted therapy, immunotherapy and radiotherapy. Of note, innovative therapeutic regimens concern the administration of multitarget drugs in tandem, in order to improve therapeutic efficacy. However, also, if this drug combination is clinically relevant, the patient’s response is not yet optimal. In this scenario, nanotechnology-based delivery systems can play a crucial role in the clinical treatment of advanced melanoma. In fact, their nano-features enable targeted drug delivery at a cellular level by overcoming biological barriers. Various nanomedicines have been proposed for the treatment of cutaneous melanoma, and a relevant number of them are undergoing clinical trials. In Italy, researchers are focusing on the pharmaceutical development of nanoformulations for malignant melanoma therapy. The present review reports an overview of the main melanoma-addressed nanomedicines currently under study in Italy, alongside the state of the art of melanoma therapy. Moreover, the latest Italian advances concerning the pre-clinical evaluation of nanomedicines for melanoma are described.
Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models
Authors: Kiisholts Kristina , Kurrikoff Kaido , Arukuusk Piret , Porosk Ly , Peters Maire , Salumets Andres , Langel Ülo
Published: October 2021

Gene therapy is a powerful tool for the development of new treatment strategies for various conditions, by aiming to transport biologically active nucleic acids into diseased cells. To achieve that goal, we used highly potential delivery vectors, cell-penetrating peptides (CPPs), as oligonucleotide carriers for the development of a therapeutic approach for endometriosis and cancer. Despite marked differences, both of these conditions still exhibit similarities, like excessive, uncoordinated, and autonomous cellular proliferation and invasion, accompanied by overlapping gene expression patterns. Thus, in the current study, we investigated the therapeutic effects of CPP and siRNA nanoparticles using in vitro models of benign endometriosis and malignant glioblastoma. We demonstrated that CPPs PepFect6 and NickFect70 are highly effective in transfecting cell lines, primary cell cultures, and three-dimensional spheroids. CPP nanoparticles are capable of inducing siRNA-specific knockdown of therapeutic genes, ribonucleotide reductase subunit M2 (RRM2), and vascular endothelial growth factor (VEGF), which results in the reduction of in vitro cellular proliferation, invasion, and migration. In addition, we proved that it is possible to achieve synergistic suppression of endometriosis cellular proliferation and invasion by combining gene therapy and hormonal treatment approaches by co-administering CPP/siRNA nanoparticles together with the endometriosis-drug danazol. We suggest a novel target, RRM2, for endometriosis therapy and as a proof-of-concept, we propose a CPP-mediated gene therapy approach for endometriosis and cancer.
Therapeutic Liquid Formulations Based on Low Transition Temperature Mixtures for the Incorporation of Anti-Inflammatory Drugs
Authors: Roda Ana , Paiva Alexandre , Duarte Ana Rita C.
Published: October 2021

Most nonsteroidal anti-inflammatory drugs (NSAIDs) present poor aqueous solubility, impairing their efficiency in physiological media. In this context, Low Transition Temperature Mixtures (LTTMs) are a promising platform to overcome drugs’ poor solubility, forming therapeutic liquid formulations. In this work, the LTTMs of citric acid:L-arginine:water (C:A:W) and glycerol:sorbitol (G:S) were studied in terms of their features and assessed in terms of their ability to increase the solubility of six NSAIDs in physiological media. The physicochemical properties of LTTMs were characterized by state-of-art techniques commonly used for these systems. The cytotoxicity of G:S was also evaluated in L929 mouse fibroblasts and the viscosity, polarity, and pH properties of the studied mixtures were related to the solubility of NSAIDs. The pH and polarity were the parameters that most influenced the drugs’ solubility. Ibuprofen, naproxen, ketoprofen, indomethacin, and flurbiprofen did not present any solubility improvement in the formulations tested. However, concentrated mixtures of C:A:W or G:S in the physiologic-mimicked media (PBS) rendered a celecoxib solubility 4 and 5 times higher than PBS, respectively. These therapeutic liquid formulations of celecoxib in C:A:W or G:S can be a promising tool to increase celecoxib’s therapeutic efficiency in local applications.
Functionalizing Ferritin Nanoparticles for Vaccine Development
Authors: Rodrigues Margarida Q. , Alves Paula M. , Roldão António
Published: October 2021

In the last decade, the interest in ferritin-based vaccines has been increasing due to their safety and immunogenicity. Candidates against a wide range of pathogens are now on Phase I clinical trials namely for influenza, Epstein-Barr, and SARS-CoV-2 viruses. Manufacturing challenges related to particle heterogeneity, improper folding of fused antigens, and antigen interference with intersubunit interactions still need to be overcome. In addition, protocols need to be standardized so that the production bioprocess becomes reproducible, allowing ferritin-based therapeutics to become readily available. In this review, the building blocks that enable the formulation of ferritin-based vaccines at an experimental stage, including design, production, and purification are presented. Novel bioengineering strategies of functionalizing ferritin nanoparticles based on modular assembly, allowing the challenges associated with genetic fusion to be circumvented, are discussed. Distinct up/down-stream approaches to produce ferritin-based vaccines and their impact on production yield and vaccine efficacy are compared. Finally, ferritin nanoparticles currently used in vaccine development and clinical trials are summarized.
RETRACTED: Ceftriaxone and Melittin Synergistically Promote Wound Healing in Diabetic Rats
Authors: Alhakamy Nabil , Caruso Giuseppe , Eid Basma , Fahmy Usama , Ahmed Osama , Abdel-Naim Ashraf , Alamoudi Abdulmohsin , Alghamdi Shareefa , Al Sadoun Hadeel , Eldakhakhny Basmah , Caraci Filippo , Abdulaal Wesam
Published: October 2021

High glucose levels in diabetic patients are implicated in delay wound healing that could lead to more serious clinical complications. The aim of the present work was to examine the formulation of ceftriaxone (CTX) and melittin (MEL) as nanoconjugate (nanocomplex)-loaded hydroxypropyl methylcellulose (HPMC) (1.5% w/v)-based hydrogel for healing of acute wounds in diabetic rats. The CTX–MEL nanoconjugate, formulated by ion-pairing at different molar ratio, was characterized for size and zeta potential and investigated by transmission electron microscopy. CTX–MEL nanoconjugate was prepared, and its preclinical efficacy evaluated in an in vivo model of acute wound. In particular, the potential ability of the innovative CTX–MEL formulation to modulate wound closure, oxidative status, inflammatory markers, and hydroxyproline was evaluated by ELISA, while the histopathological examination was obtained by using hematoxylin and eosin or Masson’s trichrome staining techniques. Quantitative real-time PCR (qRT-PCR) of the excised tissue to measure collagen, type I, alpha 1 (Col1A1) expression and immunohistochemical assessment of vascular endothelial growth factor A (VEGF-A) and transforming growth factor beta 1 (TGF-β1) were also carried out to shed some light on the mechanism of wound healing. Our results show that the CTX–MEL nanocomplex has enhanced ability to regenerate epithelium, also giving better keratinization, epidermal proliferation, and granulation tissue formation, compared to MEL, CTX, or positive control. The nanocomplex also significantly ameliorated the antioxidant status by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) levels. The treatment of wounded skin with the CTX–MEL nanocomplex also showed a significant reduction in interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) pro-inflammatory cytokines combined with a substantial increase in hydroxyproline, VEFG-A, and TGF-β1 protein expression compared to individual components or negative control group. Additionally, the CTX–MEL nanocomplex showed a significant increase in mRNA expression levels of Col1A1 as compared to individual compounds. In conclusion, the ion-pairing nanocomplex of CTX–MEL represents a promising carrier that can be topically applied to improve wound healing.
Iron Oxide Nanoparticles Carrying 5-Fluorouracil in Combination with Magnetic Hyperthermia Induce Thrombogenic Collagen Fibers, Cellular Stress, and Immune Responses in Heterotopic Human Colon Cancer in Mice
Authors: Dabaghi Mohammad , Rasa Seyed Mohammad Mahdi , Cirri Emilio , Ori Alessandro , Neri Francesco , Quaas Rainer , Hilger Ingrid
Published: October 2021

In this study we looked for the main protein pathway regulators which were responsible for the therapeutic impact on colon cancers when combining magnetic hyperthermia with the chemotherapeutic agent 5-fluorouracil (5FU). To this end, chitosan-coated magnetic nanoparticles (MNP) functionalized with 5FU were intratumorally injected into subcutaneous human colon cancer xenografts (HT-29) in mice and exposed to an alternating magnetic field. A decreased tumor growth was found particularly for the combined thermo-chemotherapy vs. the corresponding monotherapies. By using computational analysis of the tumor proteome, we found upregulated functional pathway categories termed “cellular stress and injury”, “intracellular second messenger and nuclear receptor signaling”, “immune responses”, and “growth proliferation and development”. We predict TGF-beta, and other mediators, as important upstream regulators. In conclusion, our findings show that the combined thermo-chemotherapy induces thrombogenic collagen fibers which are able to impair tumor nutrient supply. Further on, we associate several responses to the recognition of damage associated molecular patterns (DAMPs) by phagocytic cells, which immigrate into the tumor area. The activation of some pathways associated with cell survival implies the necessity to conduct multiple therapy sessions in connection with a corresponding monitoring, which could possibly be performed on the base of the identified protein regulators.
Integration of Transcriptomics and Metabolomics to Reveal the Molecular Mechanisms Underlying Rhodium Nanoparticles-Based Photodynamic Cancer Therapy
Authors: Machuca Andres , Garcia-Calvo Estefania , Anunciação Daniela S. , Luque-Garcia Jose L.
Published: October 2021

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in a specific area, thus avoiding undesirable side effects on healthy tissues. In this study, a multi-omics approach based on the combination of microarray-based transcriptomics and mass spectrometry-based untargeted and targeted metabolomics has provided a global picture of the molecular mechanisms underlying the anti-tumoral effect of rhodium nanoparticle-based photodynamic therapy. The results have shown the ability of these nanoparticles to promote apoptosis by suppressing or promoting anti- and pro-apoptotic factors, respectively, and by affecting the energy machinery of tumor cells, mainly blocking the β-oxidation, which is reflected in the accumulation of free fatty acids and in the decrease in ATP, ADP and NAD+ levels.
Estimation of the Difference in Colistin Plasma Levels in Critically Ill Patients with Favorable or Unfavorable Clinical Outcomes
Authors: Sanabria Jose , Garzón Vivian , Pacheco Tatiana , Avila Maria-Paula , Garcia Julio-Cesar , Jaimes Diego , Torres Angela , Bustos Rosa-Helena , Escobar-Perez Javier , Abril Deisy
Published: October 2021

In recent decades, antimicrobial resistance (AMR) has led to an increased use of therapeutic alternatives. Among these options, colistin continues to be an option for the treatment of multi-resistant (MDR) Gram-negative bacterial infections. However, due to its high toxicity (nephrotoxicity and neurotoxicity) and narrow therapeutic window, colistin treatment must be utilized carefully. Colistin-treated patients have been observed to have higher mortality due to inadequate therapeutic levels. The objective of this study was to estimate the difference in colistin plasma levels in critically ill patients, and its relationship to favorable or unfavorable clinical outcomes. This prospective observational study was conducted between September 2017 and June 2020 at the Universidad de La Sabana Clinic, in patients who had been treated with colistimethate sodium (CMS) for at least 72 h until day 7 of drug treatment in the critical care unit of a university hospital. There were no statistically significant differences in colistin levels between groups with favorable or unfavorable clinical outcomes (0.16 SD vs. 0.54 SD p-value = 0.167). There was higher mortality in patients with subtherapeutic levels (18% vs. 0%), and additionally, there was a greater rate of renal failure in the group with higher therapeutic levels (50% vs. 20.7%). Due to the loss of power of the study, we were unable to demonstrate a possible difference between colistin levels related to favorable or unfavorable clinical outcomes at day 7. However, we recommend further studies to evaluate the impact of measuring levels in terms of mortality and security.
The Impact of Improving Dermal Permeation on the Efficacy and Targeting of Liposome Nanoparticles as a Potential Treatment for Breast Cancer
Authors: Salem Heba F. , Gamal Amr , Saeed Haitham , Tulbah Alaa S.
Published: October 2021

Breast cancer is the most frequent malignancy in women. This work focuses on developing deformable liposomes as a potential carrier for breast cancer treatment and studying the impact of improving dermal permeation on the efficacy and targeting of liposomes. Raloxifene (RXF), an oestrogen antagonist, was used as a model drug. Using Box–Behnken design, different formulations of RXF-loaded deformable liposome (RLDL) were prepared using different propylene glycol, phospholipid and cholesterol concentrations. The percentage of entrapment efficiency (Y1), particle size (Y2), zeta potential (Y3) and steady-state flux (Y4) of the prepared formulations were all evaluated. Y1 and Y4 were significantly increased and Y2 and Y3 were significantly decreased when the propylene glycol concentration was increased. The optimization was obtained and the optimum formulation was that including phospholipid (1.40% w/w), cholesterol (0.15% w/w) and propylene glycol (10% v/v). The selected optimum formulation displayed a % EE of 78.34 ± 1.04% with a steady-state flux of 4.21 ± 0.02 µg/cm2/h. In order to investigate bioavailability, antitumor effectiveness and permeation, the optimum formulation was selected and included in a carbopol gel. The optimum gel formulation had 2.77 times higher bioavailability and, as a result, considerable antitumor action as compared to oral RXF. In conclusion, optimum RLDL gel may be an effective breast cancer treatment.
Shape Measurement Method of Two-Dimensional Micro-Structures beyond the Diffraction Limit Based on Speckle Interferometry
Authors: Arai Yasuhiko
Published: October 2021

A technique based on speckle interferometry for observing microstructures beyond the diffraction limit by detecting the spatial phase distribution of scattered light from microstructures has previously been reported. In this study, the development of this technique using a two-dimensional method is discussed. In order to observe general two-dimensional images, development of new technology in several stages is required. A two-dimensional filtering technique to reduce the noise component and a two-dimensional integration path to detect the three-dimensional shape of the surface are described in detail. As a first step toward observing complex two-dimensional structures in the future, it is investigated that directional two-dimensional information such as fibrous materials and micro-linear structures can be visually captured and treated as meaningful two-dimensional structures. As a result, it is shown that it is possible to observe fine two-dimensional letters with a line width of 100 nm, which is beyond the diffraction limit of the objective lens, demonstrating the effectiveness of the observation technique for microstructures by phase detection.
Multimodal and Multiview Wound Monitoring with Mobile Devices
Authors: Gutierrez Evelyn , Castañeda Benjamín , Treuillet Sylvie , Hernandez Ivan
Published: October 2021

Along with geometric and color indicators, thermography is another valuable source of information for wound monitoring. The interaction of geometry with thermography can provide predictive indicators of wound evolution; however, existing processes are focused on the use of high-cost devices with a static configuration, which restricts the scanning of large surfaces. In this study, we propose the use of commercial devices, such as mobile devices and portable thermography, to integrate information from different wavelengths onto the surface of a 3D model. A handheld acquisition is proposed in which color images are used to create a 3D model by using Structure from Motion (SfM), and thermography is incorporated into the 3D surface through a pose estimation refinement based on optimizing the temperature correlation between multiple views. Thermal and color 3D models were successfully created for six patients with multiple views from a low-cost commercial device. The results show the successful application of the proposed methodology where thermal mapping on 3D models is not limited in the scanning area and can provide consistent information between multiple thermal camera views. Further work will focus on studying the quantitative metrics obtained by the multi-view 3D models created with the proposed methodology.
Intraoperative Control of Hemoglobin Oxygen Saturation in the Intestinal Wall during Anastomosis Surgery
Authors: Kustov Daniil M. , Savelieva Tatiana A. , Mironov Timofey A. , Kharnas Sergey S. , Levkin Vladimir V. , Gorbunov Andrey S. , Shiryaev Artem A. , Loschenov Victor B.
Published: October 2021

During surgery for colon cancer, monitoring of the oxygen saturation of hemoglobin in the tissues under study makes it possible to assess the degree of blood supply to the anastomosis areas of the colon. Adequate blood supply in this area is decisive in terms of the consistency of the anastomosis and can significantly reduce the risk leakage of anastomosis. In this work, we propose a new approach to assessing the hemoglobin oxygen saturation based on measuring both the diffuse reflectance and transmittance spectra of the colon wall tissues. The proposed method is based on the use of two fiber-optic tools for irradiation from both sides—the intestinal lumen and the outside of the intestinal wall. The spectra are recorded from the external side. To determine the degree of hemoglobin saturation, two algorithms, both based on the Taylor series expansion of the coefficient of light attenuation by tissues, are proposed. The results of a clinical study of the proposed approach on volunteers were obtained, allowing to draw a conclusion about the applicability of the approach in a clinical setting.
Intelligent Matching of the Control Voltage of Delay Line Interferometers for Differential Phase Shift Keying-Modulated Optical Signals
Authors: Zhou Jing , Liang Duandan
Published: October 2021

In optical communications, differential phase shift keying (DPSK) provides a desired modulation format that offers high tolerance to nonlinear effects in high-speed transmissions. A DPSK demodulator converts the phase-coded signal into an intensity-coded signal at receivers. One demodulation scheme is called balanced detection and is based on a tunable delay line interferometer (DLI). Demodulation performances are determined by the phase delay generated by the DLI, while the phase delay is controlled by a tunable driving voltage on the DLI device. However, a problem in the dynamic adjustment of the control voltage prevents the application of DPSK demodulators. The receivers need to scan the whole control voltage range of the DLI and find the control voltage that maximizes the demodulation performance, but the scan-based method needs to undergo a very long searching time. In our work, we found that the relation between DLI control voltages and demodulation performance can be predicted rapidly by a feedforward neural network (FNN). In this paper, we propose a new method to quickly locate the best DLI control voltage based on an FNN. We also verify the proposed method in simulations and telecommunication systems, and the results show that the proposed method can significantly improve the efficiency of resolving the best demodulation voltages.
III-Nitride Light-Emitting Devices
Authors: Baten Md Zunaid , Alam Shamiul , Sikder Bejoy , Aziz Ahmedullah
Published: October 2021

III-nitride light-emitting devices have been subjects of intense research for the last several decades owing to the versatility of their applications for fundamental research, as well as their widespread commercial utilization. Nitride light-emitters in the form of light-emitting diodes (LEDs) and lasers have made remarkable progress in recent years, especially in the form of blue LEDs and lasers. However, to further extend the scope of these devices, both below and above the blue emission region of the electromagnetic spectrum, and also to expand their range of practical applications, a number of issues and challenges related to the growth of materials, device design, and fabrication need to be overcome. This review provides a detailed overview of nitride-based LEDs and lasers, starting from their early days of development to the present state-of-the-art light-emitting devices. Besides delineating the scientific and engineering milestones achieved in the path towards the development of the highly matured blue LEDs and lasers, this review provides a sketch of the prevailing challenges associated with the development of long-wavelength, as well as ultraviolet nitride LEDs and lasers. In addition to these, recent progress and future challenges related to the development of next-generation nitride emitters, which include exciton-polariton lasers, spin-LEDs and lasers, and nanostructured emitters based on nanowires and quantum dots, have also been elucidated in this review. The review concludes by touching on the more recent topic of hexagonal boron nitride-based light-emitting devices, which have already shown significant promise as deep ultraviolet and single-photon emitters.
Genetic Mapping of the HLA1 Locus Causing Hybrid Lethality in Nicotiana Interspecific Hybrids
Authors: Tezuka Takahiro , Kitamura Naoto , Imagawa Sae , Hasegawa Akira , Shiragaki Kumpei , He Hai , Yanase Masanori , Ogata Yoshiyuki , Morikawa Toshinobu , Yokoi Shuji
Published: October 2021

Hybrid lethality, a postzygotic mechanism of reproductive isolation, is a phenomenon that causes the death of F1 hybrid seedlings. Hybrid lethality is generally caused by the epistatic interaction of two or more loci. In the genus Nicotiana, N. debneyi has the dominant allele Hla1-1 at the HLA1 locus that causes hybrid lethality in F1 hybrid seedlings by interaction with N. tabacum allele(s). Here, we mapped the HLA1 locus using the F2 population segregating for the Hla1-1 allele derived from the interspecific cross between N. debneyi and N. fragrans. To map HLA1, several DNA markers including random amplified polymorphic DNA, amplified fragment length polymorphism, and simple sequence repeat markers, were used. Additionally, DNA markers were developed based on disease resistance gene homologs identified from the genome sequence of N. benthamiana. Linkage analysis revealed that HLA1 was located between two cleaved amplified polymorphic sequence markers Nb14-CAPS and NbRGH1-CAPS at a distance of 10.8 and 10.9 cM, respectively. The distance between these markers was equivalent to a 682 kb interval in the genome sequence of N. benthamiana.
Development of SNP Set for the Marker-Assisted Selection of Guar (Cyamopsis tetragonoloba (L.) Taub.) Based on a Custom Reference Genome Assembly
Authors: Grigoreva Elizaveta , Barbitoff Yury , Changalidi Anton , Karzhaev Dmitry , Volkov Vladimir , Shadrina Veronika , Safronycheva Elizaveta , Ben Cécile , Gentzbittel Laurent , Potokina Elena
Published: October 2021

Guar gum, a polysaccharide derived from guar seeds, is widely used in a variety of industrial applications, including oil and gas production. Although guar is mostly propagated in India, interest in guar as a new industrial legume crop is increasing worldwide, demanding the development of effective tools for marker-assisted selection. In this paper, we report a wide-ranging set of 4907 common SNPs and 327 InDels generated from RADseq genotyping data of 166 guar plants of different geographical origin. A custom guar reference genome was assembled and used for variant calling. A consensus set of variants was built using three bioinformatic pipelines for short variant discovery. The developed molecular markers were used for genome-wide association study, resulting in the discovery of six markers linked to the variation of an important agronomic trait—percentage of pods matured to the harvest date under long light day conditions. One of the associated variants was found inside the putative transcript sequence homologous to an ABC transporter in Arabidopsis, which has been shown to play an important role in D-myo-inositol phosphates metabolism. Earlier, we suggested that genes involved in myo-inositol phosphate metabolism have significant impact on the early flowering of guar plants. Hence, we believe that the developed SNP set allows for the identification of confident molecular markers of important agrobiological traits.
Biochemical and Molecular Characterization of the Rice Chalcone Isomerase Family
Authors: Park Sang-Il , Park Hye-Lin , Bhoo Seong-Hee , Lee Sang-Won , Cho Man-Ho
Published: October 2021

Chalcone isomerase (CHI) is a key enzyme in flavonoid biosynthesis. In plants, CHIs occur in multigene families, and they are divided into four types, types I–IV. Type I and II CHIs are bona fide CHIs with CHI activity, and type III and IV CHIs are non-catalytic members with different functions. Rice contains seven CHI family genes (OsCHIs). Molecular analysis suggested that OsCHI3 is a type I CHI, and the other OsCHIs were classified into types III and IV. To elucidate their biochemical functions, OsCHI1, OsCHI3, OsCHI6, and OsCHI7 were expressed in Escherichia coli, and the recombinant OsCHI proteins were purified. An activity assay of recombinant OsCHIs showed that OsCHI3 catalyzed the isomerization of naringenin chalcone and isoliquiritigenin, whereas the other recombinant OsCHIs had no CHI activity. OsCHI3 also exhibited a strong preference to naringenin chalcone compared to isoliquiritigenin, which agrees well with the catalytic properties of type I CHIs. These results ascertain OsCHI3 to be a bona fide CHI in rice. OsCHI3 and the other OsCHIs were expressed constitutively throughout the rice growth period and different tissues. OsCHI3 expression was induced immediately in response to ultra-violet (UV) stress, suggesting its involvement in the biosynthesis of sakuranetin, a flavonoid phytoalexin in rice.
Metabolomic Analysis on the Petal of ‘Chen Xi’ Rose with Light-Induced Color Changes
Authors: Su Mengyue , Damaris Rebecca Njeri , Hu Zhengrong , Yang Pingfang , Deng Jiao
Published: October 2021

Flower color is one of the most prominent traits of rose flowers and determines their ornamental value. The color of the “Chen Xi” rose can change from yellow to red during flower blooming. In the present study, the flavonoid metabolites were investigated by the UPLC-ESI-MS/MS from the petals of four successive flower development stages under natural conditions. In total, 176 flavonoid components, including 49 flavones, 59 flavonols, 12 flavanones, 3 isoflavones, 12 anthocyanins, and 41 proanthocyanidins were identified, with some of them being detected for the first time in this study. Additionally, there were 56 compounds that showed differences among comparison groups, mainly being enriched in pathways of isoflavone, flavonoid, flavone, flavonol, phenylpropanoids, and anthocyanin. Among them, it is anthocyanins that allow the rose flower to turn red when exposed to sunlight. To verify this result, compounds from rose petal with shading treatment (S2D) was also detected but could be clearly separated from the four samples under light by clustering and principal component analyses (PCA). Consistent with low anthocyanins accumulation, the flower with shading could not turn red. Moreover, it provides a foundation for further research on the light-induced color modification of flower.
Exogenous Application of Methyl Jasmonate and Salicylic Acid Mitigates Drought-Induced Oxidative Damages in French Bean (Phaseolus vulgaris L.)
Authors: Mohi-Ud-Din Mohammed , Talukder Dipa , Rohman Motiar , Ahmed Jalal Uddin , Jagadish S. V. Krishna , Islam Tofazzal , Hasanuzzaman Mirza
Published: October 2021

Drought stress impairs the normal growth and development of plants through various mechanisms including the induction of cellular oxidative stresses. The aim of this study was to evaluate the effect of the exogenous application of methyl jasmonate (MeJA) and salicylic acid (SA) on the growth, physiology, and antioxidant defense system of drought-stressed French bean plants. Application of MeJA (20 μM) or SA (2 mM) alone caused modest reductions in the harmful effects of drought. However, combined application substantially enhanced drought tolerance by improving the physiological activities and antioxidant defense system. The drought-induced generation of O2●− and H2O2, the MDA content, and the LOX activity were significantly lower in leaves when seeds or leaves were pre-treated with a combination of MeJA (10 μM) and SA (1 mM) than with either hormone alone. The combined application of MeJA and SA to drought-stressed plants also significantly increased the activities of the major antioxidant enzymes superoxide dismutase, catalase, peroxidase, glutathione peroxidase, and glutathione-S-transferase as well as the enzymes of the ascorbate–glutathione cycle. Taken together, our results suggest that seed or foliar application of a combination of MeJA and SA restore growth and normal physiological processes by triggering the antioxidant defense system in drought-stressed plants.