International Journal of Molecular Sciences

21 pages, 6374 KiB

Open AccessArticle

Incorporation of the New anti-Octadecaborane Laser Dyes into Thin Polymer Films: A Temperature-Dependent Photoluminescence and Infrared Spectroscopy Study

by Tereza Capkova, Barbora Hanulikova, Jakub Sevcik, Pavel Urbanek, Jan Antos, Michal Urbanek and Ivo Kuritka

Int. J. Mol. Sci. 2022, 23(15), 8832; https://doi.org/10.3390/ijms23158832 - 8 Aug 2022

Cited by 1 | Viewed by 2151

Abstract

New anti-octadecaborane(22) laser dyes have been recently introduced. However, their application in solid thin films is limited, despite being very desirable for electronics. Spectroscopic methods, photoluminescence (PL), and infrared reflection–absorption spectroscopy (IRRAS), are here used to reveal structural responses to a temperature [...] Read more.

New anti-octadecaborane(22) laser dyes have been recently introduced. However, their application in solid thin films is limited, despite being very desirable for electronics. Spectroscopic methods, photoluminescence (PL), and infrared reflection–absorption spectroscopy (IRRAS), are here used to reveal structural responses to a temperature change in thin polymer films made of π- and σ-conjugated and non-conjugated polymers and anti-octadecaborane(22) and its tetra-alkylatedderivatives. It has been observed that borane clusters are not firmly fixed within polymer matrices and that their ability for diffusion out of the polymer film is unprecedented, especially at higher temperatures. This ability is related to thermodynamic transitions of polymer macromolecular chains. PL and IRRAS spectra have revealed a clear correlation with β-transition and α-transition of polymers. The influence of structure and molecular weight of a polymer and the concentration and the substitution type of clusters on mobility of borane clusters within the polymer matrix is demonstrated. A solution is proposed that led to an improvement of the temperature stability of films by 45 °C. The well-known spectroscopic methods have proved to be powerful tools for a non-routine description of the temperature behavior of both borane clusters and polymer matrices. Full article

(This article belongs to the Section Materials Science)

► Show Figures

Graphical abstract

18 pages, 2728 KiB

Open AccessArticle

Differential Expression of miRNAs and Their Predicted Target Genes Indicates That Gene Expression in Atlantic Salmon Gill Is Post-Transcriptionally Regulated by miRNAs in the Parr-Smolt Transformation and Adaptation to Sea Water

by Alice Shwe, Aleksei Krasnov, Tina Visnovska, Sigmund Ramberg, Tone-Kari K. Østbye and Rune Andreassen

Int. J. Mol. Sci. 2022, 23(15), 8831; https://doi.org/10.3390/ijms23158831 - 8 Aug 2022

Cited by 5 | Viewed by 2940

Abstract

Smoltification (parr-smolt transformation) is a complex developmental process consisting of developmental changes that lead to remodeling of the Atlantic salmon gill. Here, the expression changes of miRNAs and mRNAs were studied by small-RNA sequencing and microarray analysis, respectively, to identify miRNAs and their [...] Read more.

Smoltification (parr-smolt transformation) is a complex developmental process consisting of developmental changes that lead to remodeling of the Atlantic salmon gill. Here, the expression changes of miRNAs and mRNAs were studied by small-RNA sequencing and microarray analysis, respectively, to identify miRNAs and their predicted targets associated with smoltification and subsequent sea water adaptation (SWA). In total, 18 guide miRNAs were identified as differentially expressed (gDE miRNAs). Hierarchical clustering analysis of expression changes divided these into one cluster of 13 gDE miRNAs with decreasing expression during smoltification and SWA that included the miRNA-146, miRNA-30 and miRNA-7132 families. Another smaller cluster that showed increasing expression consisted of miR-101a-3p, miR-193b-5p, miR-499a-5p, miR-727a-3p and miR-8159-5p. The gDE miRNAs were predicted to target 747 of the genes (DE mRNAs), showing expression changes in the microarray analysis. The predicted targets included genes encoding NKA-subunits, aquaporin-subunits, cystic fibrosis transmembrane conductance regulator and the solute carrier family. Furthermore, the predicted target genes were enriched in biological processes associated with smoltification and SWA (e.g., immune system, reactive oxygen species, stress response and extracellular matrix organization). Collectively, the results indicate that remodeling of the gill involves the post-transcriptional regulation of gene expression by the characterized gDE miRNAs. Full article

(This article belongs to the Special Issue Noncoding RNAs: Molecular Mechanisms and Physio-Pathological Implications)

► Show Figures

Figure 1

15 pages, 7801 KiB

Open AccessArticle

Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS

by Radu Nicolae Revnic, Gabriela Fabiola Știufiuc, Valentin Toma, Anca Onaciu, Alin Moldovan, Adrian Bogdan Țigu, Eva Fischer-Fodor, Romulus Tetean, Emil Burzo and Rareș Ionuț Știufiuc

Int. J. Mol. Sci. 2022, 23(15), 8830; https://doi.org/10.3390/ijms23158830 - 8 Aug 2022

Cited by 5 | Viewed by 3337

Abstract

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have [...] Read more.

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag⁺ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars’ physical properties. Full article

(This article belongs to the Special Issue Multifunctional Nanomaterials: Synthesis, Properties, and Applications 2.0)

► Show Figures

Figure 1

7 pages, 609 KiB

Open AccessCase Report

Ketogenic and Low FODMAP Diet in Therapeutic Management of a Young Autistic Patient with Epilepsy and Dysmetabolism Poorly Responsive to Therapies: Clinical Response and Effects of Intestinal Microbiota

by Alexander Bertuccioli, Marco Cardinali, Francesco Di Pierro, Giordano Bruno Zonzini and Maria Rosaria Matera

Int. J. Mol. Sci. 2022, 23(15), 8829; https://doi.org/10.3390/ijms23158829 - 8 Aug 2022

Cited by 8 | Viewed by 3471

Abstract

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may [...] Read more.

Autism spectrum disorder (ASD) is often associated with several intestinal and/or metabolic disorders as well as neurological manifestations such as epilepsy (ASD-E). Those presenting these neuropathological conditions share common aspects in terms of gut microbiota composition. The use of microbiota intervention strategies may be an approach to consider in the management of these cases. We describe the case of a 17-year-old girl affected by ASD, reduced growth, neurological development delay, mutations in the PGM1 and EEF1A2 genes (in the absence of clinically manifested disease) and, intestinal disorders such as abdominal pain and diarrhea associated with weight loss. As she demonstrated poor responsiveness to the therapies provided, we attempted two specific dietary patterns: a ketogenic diet, followed by a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, with the aim of improving her neurological, metabolic, and intestinal symptoms through modulation of the gut microbiota’s composition. The ketogenic diet (KD) provided a reduction in Firmicutes, Bacteroidetes, and Proteobacteria. Although her intestinal symptoms improved, KD was poorly tolerated. On the other hand, the passage to a low FODMAPs diet produced a significant improvement in all neurological, intestinal, and metabolic symptoms and was well-tolerated. The following gut microbiota analysis showed reductions in Actinobacteria, Firmicutes, Lactobacilli, and Bifidobacteria. The alpha biodiversity was consistently increased and the Firmicutes/Bacteroidetes ratio decreased, reducing the extent of fermentative dysbiosis. Gut microbiota could be a therapeutic target to improve ASD-related symptoms. Further studies are needed to better understand the correlation between gut microbiota composition and ASD, and its possible involvement in the physiopathology of ASD. Full article

(This article belongs to the Special Issue Gut Microbiota Colonization and Food Impact)

► Show Figures

Figure 1

17 pages, 4693 KiB

Open AccessArticle

Deletion of Meg8-DMR Enhances Migration and Invasion of MLTC-1 Depending on the CTCF Binding Sites

by Xiao Han, Hongjuan He, Lan Shao, Shuang Cui, Haoran Yu, Ximeijia Zhang and Qiong Wu

Int. J. Mol. Sci. 2022, 23(15), 8828; https://doi.org/10.3390/ijms23158828 - 8 Aug 2022

Cited by 5 | Viewed by 2432

Abstract

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. [...] Read more.

The Dlk1-Dio3 imprinted domain on mouse chromosome 12 contains three well-characterized paternally methylated differentially methylated regions (DMRs): IG-DMR, Gtl2-DMR, and Dlk1-DMR. These DMRs control the expression of many genes involved in embryonic development, inherited diseases, and human cancer in this domain. The first maternal methylation DMR discovered in this domain was the Meg8-DMR, the targets and biological function of which are still unknown. Here, using an enhancer-blocking assay, we first dissected the functional parts of the Meg8-DMR and showed that its insulator activity is dependent on the CCCTC-binding factor (CTCF) in MLTC-1. Results from RNA-seq showed that the deletion of the Meg8-DMR and its compartment CTCF binding sites, but not GGCG repeats, lead to the downregulation of numerous genes on chromosome 12, in particular the drastically reduced expression of Dlk1 and Rtl1 in the Dlk1-Dio3 domain, while differentially expressed genes are enriched in the MAPK pathway. In vitro assays revealed that the deletion of the Meg8-DMR and CTCF binding sites enhances cell migration and invasion by decreasing Dlk1 and activating the Notch1-Rhoc-MAPK/ERK pathway. These findings enhance research into gene regulation in the Dlk1-Dio3 domain by indicating that the Meg8-DMR functions as a long-range regulatory element which is dependent on CTCF binding sites and affects multiple genes in this domain. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

► Show Figures

Figure 1

18 pages, 705 KiB

Open AccessReview

Extracellular Vesicles in Myeloid Neoplasms

by Christina Karantanou, Valentina René Minciacchi and Theodoros Karantanos

Int. J. Mol. Sci. 2022, 23(15), 8827; https://doi.org/10.3390/ijms23158827 - 8 Aug 2022

Cited by 2 | Viewed by 3048

Abstract

Myeloid neoplasms arise from malignant primitive cells, which exhibit growth advantage within the bone marrow microenvironment (BMM). The interaction between these malignant cells and BMM cells is critical for the progression of these diseases. Extracellular vesicles (EVs) are lipid bound vesicles secreted into [...] Read more.

Myeloid neoplasms arise from malignant primitive cells, which exhibit growth advantage within the bone marrow microenvironment (BMM). The interaction between these malignant cells and BMM cells is critical for the progression of these diseases. Extracellular vesicles (EVs) are lipid bound vesicles secreted into the extracellular space and involved in intercellular communication. Recent studies have described RNA and protein alterations in EVs isolated from myeloid neoplasm patients compared to healthy controls. The altered expression of various micro-RNAs is the best-described feature of EVs of these patients. Some of these micro-RNAs induce growth-related pathways such as AKT/mTOR and promote the acquisition of stem cell-like features by malignant cells. Another well-described characteristic of EVs in myeloid neoplasms is their ability to suppress healthy hematopoiesis either via direct effect on healthy CD34+ cells or via alteration of the differentiation of BMM cells. These results support a role of EVs in the pathogenesis of myeloid neoplasms. mainly through mediating the interaction between malignant and BMM cells, and warrant further study to better understand their biology. In this review, we describe the reported alterations of EV composition in myeloid neoplasms and the recent discoveries supporting their involvement in the development and progression of these diseases. Full article

(This article belongs to the Special Issue Stem Cell Biology of Myeloid Neoplasms 2.0)

► Show Figures

Figure 1

12 pages, 2425 KiB

Open AccessArticle

Salicylaldehyde Suppresses IgE-Mediated Activation of Mast Cells and Ameliorates Anaphylaxis in Mice

by Tsubasa Ashikari, Masakazu Hachisu, Kazuki Nagata, Daisuke Ando, Yuki Iizuka, Naoto Ito, Kandai Ito, Yuki Ikeda, Hiroki Matsubara, Takuya Yashiro, Kazumi Kasakura and Chiharu Nishiyama

Int. J. Mol. Sci. 2022, 23(15), 8826; https://doi.org/10.3390/ijms23158826 - 8 Aug 2022

Cited by 3 | Viewed by 2590

Abstract

Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines [...] Read more.

Mast cells (MCs) play key roles in IgE-mediated immunoresponses, including in the protection against parasitic infections and the onset and/or symptoms of allergic diseases. IgE-mediated activation induces MCs to release mediators, including histamine and leukotriene, as an early response, and to produce cytokines as a late phase response. Attempts have been made to identify novel antiallergic compounds from natural materials such as Chinese medicines and food ingredients. We herein screened approximately 60 compounds and identified salicylaldehyde, an aromatic aldehyde isolated from plant essential oils, as an inhibitor of the IgE-mediated activation of MCs. A degranulation assay, flow cytometric analyses, and enzyme-linked immunosorbent assays revealed that salicylaldehyde inhibited the IgE-mediated degranulation and cytokine expression of bone-marrow-derived MCs (BMMCs). The salicylaldehyde treatment reduced the surface expression level of FcεRI, the high affinity receptor for IgE, on BMMCs, and suppressed the IgE-induced phosphorylation of tyrosine residues in intercellular proteins, possibly Lyn, Syk, and Fyn, in BMMCs. We also examined the effects of salicylaldehyde in vivo using passive anaphylaxis mouse models and found that salicylaldehyde administration significantly enhanced the recovery of a reduced body temperature due to systemic anaphylaxis and markedly suppressed ear swelling, footpad swelling, and vascular permeability in cutaneous anaphylaxis. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Allergy and Asthma 2.0)

► Show Figures

Figure 1

14 pages, 2224 KiB

Open AccessArticle

OsWRKY114 Inhibits ABA-Induced Susceptibility to Xanthomonas oryzae pv. oryzae in Rice

by Seungmin Son, Jong Hee Im, Giha Song, Suhyeon Nam and Sang Ryeol Park

Int. J. Mol. Sci. 2022, 23(15), 8825; https://doi.org/10.3390/ijms23158825 - 8 Aug 2022

Cited by 8 | Viewed by 2204

Abstract

The phytohormone abscisic acid (ABA) regulates various aspects of plant growth, development, and stress responses. ABA suppresses innate immunity to Xanthomonas oryzae pv. oryzae (Xoo) in rice (Oryza sativa), but the identity of the underlying regulator is unknown. In [...] Read more.

The phytohormone abscisic acid (ABA) regulates various aspects of plant growth, development, and stress responses. ABA suppresses innate immunity to Xanthomonas oryzae pv. oryzae (Xoo) in rice (Oryza sativa), but the identity of the underlying regulator is unknown. In this study, we revealed that OsWRKY114 is involved in the ABA response during Xoo infection. ABA-induced susceptibility to Xoo was reduced in OsWRKY114-overexpressing rice plants. OsWRKY114 attenuated the negative effect of ABA on salicylic acid-dependent immunity. Furthermore, OsWRKY114 decreased the transcript levels of ABA-associated genes involved in ABA response and biosynthesis. Moreover, the endogenous ABA level was lower in OsWRKY114-overexpressing plants than in the wild-type plants after Xoo inoculation. Taken together, our results suggest that OsWRKY114 is a negative regulator of ABA that confers susceptibility to Xoo in rice. Full article

(This article belongs to the Special Issue Plant Disease Resistance 2.0)

► Show Figures

Figure 1

16 pages, 2041 KiB

Open AccessArticle

Aberrant Splicing of INS Impairs Beta-Cell Differentiation and Proliferation by ER Stress in the Isogenic iPSC Model of Neonatal Diabetes

by Alexandra V. Panova, Natalia V. Klementieva, Anna V. Sycheva, Elena V. Korobko, Anastasia O. Sosnovtseva, Tatiana S. Krasnova, Maria R. Karpova, Petr M. Rubtsov, Yulia V. Tikhonovich, Anatoly N. Tiulpakov and Sergey L. Kiselev

Int. J. Mol. Sci. 2022, 23(15), 8824; https://doi.org/10.3390/ijms23158824 - 8 Aug 2022

Cited by 9 | Viewed by 2580

Abstract

One of the causes of diabetes in infants is the defect of the insulin gene (INS). Gene mutations can lead to proinsulin misfolding, an increased endoplasmic reticulum (ER) stress and possible beta-cell apoptosis. In humans, the mechanisms underlying beta-cell failure remain [...] Read more.

One of the causes of diabetes in infants is the defect of the insulin gene (INS). Gene mutations can lead to proinsulin misfolding, an increased endoplasmic reticulum (ER) stress and possible beta-cell apoptosis. In humans, the mechanisms underlying beta-cell failure remain unclear. We generated induced pluripotent stem cells (iPSCs) from a patient diagnosed with neonatal diabetes mellitus carrying the INS mutation in the 2nd intron (c.188-31G>A) and engineered isogenic CRISPR/Cas9 mutation-corrected cell lines. Differentiation into beta-like cells demonstrated that mutation led to the emergence of an ectopic splice site within the INS and appearance of the abnormal RNA transcript. Isogenic iPSC lines differentiated into beta-like cells showed a clear difference in formation of organoids at pancreatic progenitor stage of differentiation. Moreover, MIN6 insulinoma cell line expressing mutated cDNA demonstrated significant decrease in proliferation capacity and activation of ER stress and unfolded protein response (UPR)-associated genes. These findings shed light on the mechanism underlying the pathogenesis of monogenic diabetes. Full article

(This article belongs to the Special Issue Advances, Pitfalls and Future Perspectives for CRISPR/Cas9 Mediated Genome Editing)

► Show Figures

Figure 1

12 pages, 2578 KiB

Open AccessArticle

Albumin Stimulates Epithelial Na⁺ Transport and Barrier Integrity by Activating the PI3K/AKT/SGK1 Pathway

by Mandy Laube and Ulrich H. Thome

Int. J. Mol. Sci. 2022, 23(15), 8823; https://doi.org/10.3390/ijms23158823 - 8 Aug 2022

Cited by 1 | Viewed by 2098

Abstract

Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na⁺ transport drives alveolar fluid clearance (AFC), enabling [...] Read more.

Albumin is a major serum protein and is frequently used as a cell culture supplement. It is crucially involved in the regulation of osmotic pressure and distribution of fluid between different compartments. Alveolar epithelial Na⁺ transport drives alveolar fluid clearance (AFC), enabling air breathing. Whether or not albumin affects AFC and Na⁺ transport is yet unknown. We therefore determined the acute and chronic effects of albumin on Na⁺ transport in fetal distal lung epithelial (FDLE) cells and the involved kinase pathways. Chronic BSA treatment strongly increased epithelial Na⁺ transport and barrier integrity in Ussing chambers. BSA did not elevate mRNA expression of Na⁺ transporters in FDLE cells after 24 h. Moreover, acute BSA treatment for 45 min mimicked the chronic effects. The elevated Na⁺ transport was caused by an increased maximal ENaC activity, while Na,K-ATPase activity remained unchanged. Acute and chronic BSA treatment lowered membrane permeability, confirming the increased barrier integrity observed in Ussing chambers. Western blots demonstrated an increased phosphorylation of AKT and SGK1, and PI3K inhibition abolished the stimulating effect of BSA. BSA therefore enhanced epithelial Na⁺ transport and barrier integrity by activating the PI3K/AKT/SGK1 pathway. Full article

(This article belongs to the Special Issue Channels and Transporters in Cells and Tissues 3.0)

► Show Figures

Figure 1

15 pages, 3745 KiB

Open AccessArticle

Computational Analysis of Short Linear Motifs in the Spike Protein of SARS-CoV-2 Variants Provides Possible Clues into the Immune Hijack and Evasion Mechanisms of Omicron Variant

by Anjana Soorajkumar, Ebrahim Alakraf, Mohammed Uddin, Stefan S. Du Plessis, Alawi Alsheikh-Ali and Richard K. Kandasamy

Int. J. Mol. Sci. 2022, 23(15), 8822; https://doi.org/10.3390/ijms23158822 - 8 Aug 2022

Cited by 1 | Viewed by 2446

Abstract

Short linear motifs (SLiMs) are short linear sequences that can mediate protein–protein interaction. Mimicking eukaryotic SLiMs to compete with extra- or intracellular binding partners, or to sequester host proteins is the crucial strategy of viruses to pervert the host system. Evolved proteins in [...] Read more.

Short linear motifs (SLiMs) are short linear sequences that can mediate protein–protein interaction. Mimicking eukaryotic SLiMs to compete with extra- or intracellular binding partners, or to sequester host proteins is the crucial strategy of viruses to pervert the host system. Evolved proteins in viruses facilitate minimal protein–protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about SARS-CoV-2 SLiMs is known, especially across SARS-CoV-2 variants. Through the ELM database-based sequence analysis of spike proteins from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant, namely, LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue Host-Pathogen Interaction 4.0)

► Show Figures

Figure 1

19 pages, 4424 KiB

Open AccessArticle

Effect of Saccharides Coating on Antibacterial Potential and Drug Loading and Releasing Capability of Plasma Treated Polylactic Acid Films

by Ilkay Karakurt, Kadir Ozaltin, Hana Pištěková, Daniela Vesela, Jonas Michael-Lindhard, Petr Humpolícek, Miran Mozetič and Marian Lehocky

Int. J. Mol. Sci. 2022, 23(15), 8821; https://doi.org/10.3390/ijms23158821 - 8 Aug 2022

Cited by 11 | Viewed by 2677

Abstract

More than half of the hospital-associated infections worldwide are related to the adhesion of bacteria cells to biomedical devices and implants. To prevent these infections, it is crucial to modify biomaterial surfaces to develop the antibacterial property. In this study, chitosan (CS) and [...] Read more.

More than half of the hospital-associated infections worldwide are related to the adhesion of bacteria cells to biomedical devices and implants. To prevent these infections, it is crucial to modify biomaterial surfaces to develop the antibacterial property. In this study, chitosan (CS) and chondroitin sulfate (ChS) were chosen as antibacterial coating materials on polylactic acid (PLA) surfaces. Plasma-treated PLA surfaces were coated with CS either direct coating method or the carbodiimide coupling method. As a next step for the combined saccharide coating, CS grafted samples were immersed in ChS solution, which resulted in the polyelectrolyte complex (PEC) formation. Also in this experiment, to test the drug loading and releasing efficiency of the thin film coatings, CS grafted samples were immersed into lomefloxacin-containing ChS solution. The successful modifications were confirmed by elemental composition analysis (XPS), surface topography images (SEM), and hydrophilicity change (contact angle measurements). The carbodiimide coupling resulted in higher CS grafting on the PLA surface. The coatings with the PEC formation between CS-ChS showed improved activity against the bacteria strains than the separate coatings. Moreover, these interactions increased the lomefloxacin amount adhered to the film coatings and extended the drug release profile. Finally, the zone of inhibition test confirmed that the CS-ChS coating showed a contact killing mechanism while drug-loaded films have a dual killing mechanism, which includes contact, and release killing. Full article

(This article belongs to the Special Issue SMART and Macromolecular Biomaterials: From Materials to Biology)

► Show Figures

Figure 1

19 pages, 3512 KiB

Open AccessArticle

Soil and Soilless Tomato Cultivation Promote Different Microbial Communities That Provide New Models for Future Crop Interventions

by Alice Anzalone, Alexandros Mosca, Giulio Dimaria, Daniele Nicotra, Matilde Tessitori, Grete Francesca Privitera, Alfredo Pulvirenti, Cherubino Leonardi and Vittoria Catara

Int. J. Mol. Sci. 2022, 23(15), 8820; https://doi.org/10.3390/ijms23158820 - 8 Aug 2022

Cited by 15 | Viewed by 4549

Abstract

The cultivation of soilless tomato in greenhouses has increased considerably, but little is known about the assembly of the root microbiome compared to plants grown in soil. To obtain such information, we constructed an assay in which we traced the bacterial and fungal [...] Read more.

The cultivation of soilless tomato in greenhouses has increased considerably, but little is known about the assembly of the root microbiome compared to plants grown in soil. To obtain such information, we constructed an assay in which we traced the bacterial and fungal communities by amplicon-based metagenomics during the cultivation chain from nursery to greenhouse. In the greenhouse, the plants were transplanted either into agricultural soil or into coconut fiber bags (soilless). At the phylum level, bacterial and fungal communities were primarily constituted in all microhabitats by Proteobacteria and Ascomycota, respectively. The results showed that the tomato rhizosphere microbiome was shaped by the substrate or soil in which the plants were grown. The microbiome was different particularly in terms of the bacterial communities. In agriculture, enrichment has been observed in putative biological control bacteria of the genera Pseudomonas and Bacillus and in potential phytopathogenic fungi. Overall, the study describes the different shaping of microbial communities in the two cultivation methods. Full article

(This article belongs to the Special Issue Interaction between Plants, Microorganisms, and Soils in Different Ecosystems)

► Show Figures

Figure 1

18 pages, 3725 KiB

Open AccessArticle

Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates

by Jan Samsonowicz-Górski, Dominik Koszelewski, Paweł Kowalczyk, Paweł Śmigielski, Anastasiia Hrunyk, Karol Kramkowski, Aleksandra Wypych, Mateusz Szymczak, Rafał Lizut and Ryszard Ostaszewski

Int. J. Mol. Sci. 2022, 23(15), 8819; https://doi.org/10.3390/ijms23158819 - 8 Aug 2022

Cited by 6 | Viewed by 2133

Abstract

An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for [...] Read more.

An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of β-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the β-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four β-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics. Full article

(This article belongs to the Special Issue New Types of Antibacterial Biocides)

► Show Figures

Figure 1

18 pages, 3917 KiB

Open AccessArticle

LEAF TIP RUMPLED 1 Regulates Leaf Morphology and Salt Tolerance in Rice

by Jiajia Wang, Yiting Liu, Songping Hu, Jing Xu, Jinqiang Nian, Xiaoping Cao, Minmin Chen, Jiangsu Cen, Xiong Liu, Zhihai Zhang, Dan Liu, Li Zhu, Jiang Hu, Deyong Ren, Zhenyu Gao, Lan Shen, Guojun Dong, Qiang Zhang, Qing Li, Sibin Yu, Qian Qian and Guangheng Zhang Show full author list Hide full author list

Int. J. Mol. Sci. 2022, 23(15), 8818; https://doi.org/10.3390/ijms23158818 - 8 Aug 2022

Cited by 7 | Viewed by 2557

Abstract

Leaf morphology is one of the important traits related to ideal plant architecture and is an important factor determining rice stress resistance, which directly affects yield. Wax layers form a barrier to protect plants from different environmental stresses. However, the regulatory effect of [...] Read more.

Leaf morphology is one of the important traits related to ideal plant architecture and is an important factor determining rice stress resistance, which directly affects yield. Wax layers form a barrier to protect plants from different environmental stresses. However, the regulatory effect of wax synthesis genes on leaf morphology and salt tolerance is not well-understood. In this study, we identified a rice mutant, leaf tip rumpled 1 (ltr1), in a mutant library of the classic japonica variety Nipponbare. Phenotypic investigation of NPB and ltr1 suggested that ltr1 showed rumpled leaf with uneven distribution of bulliform cells and sclerenchyma cells, and disordered vascular bundles. A decrease in seed-setting rate in ltr1 led to decreased per-plant grain yield. Moreover, ltr1 was sensitive to salt stress, and LTR1 was strongly induced by salt stress. Map-based cloning of LTR1 showed that there was a 2-bp deletion in the eighth exon of LOC_Os02g40784 in ltr1, resulting in a frameshift mutation and early termination of transcription. Subsequently, the candidate gene was confirmed using complementation, overexpression, and knockout analysis of LOC_Os02g40784. Functional analysis of LTR1 showed that it was a wax synthesis gene and constitutively expressed in entire tissues with higher relative expression level in leaves and panicles. Moreover, overexpression of LTR1 enhanced yield in rice and LTR1 positively regulates salt stress by affecting water and ion homeostasis. These results lay a theoretical foundation for exploring the molecular mechanism of leaf morphogenesis and stress response, providing a new potential strategy for stress-tolerance breeding. Full article

(This article belongs to the Special Issue Research on Plant Genomics and Breeding)

► Show Figures

Figure 1

9 pages, 1248 KiB

Open AccessBrief Report

Hyaluronic Acid Alleviates Oxidative Stress and Apoptosis in Human Tenocytes via Caspase 3 and 7

by Marialucia Gallorini, Cristina Antonetti Lamorgese Passeri, Amelia Cataldi, Anna Concetta Berardi and Leonardo Osti

Int. J. Mol. Sci. 2022, 23(15), 8817; https://doi.org/10.3390/ijms23158817 - 8 Aug 2022

Cited by 9 | Viewed by 2077

Abstract

Rotator cuff tendinopathy (RCT) is the primary reason for shoulder surgery and its clinical management is still challenging. Hyaluronic acid (HA) has been shown to have anti-inflammatory effects in vitro and in vivo under RCT conditions, characterized by an exaggerated oxidative stress (OS). [...] Read more.

Rotator cuff tendinopathy (RCT) is the primary reason for shoulder surgery and its clinical management is still challenging. Hyaluronic acid (HA) has been shown to have anti-inflammatory effects in vitro and in vivo under RCT conditions, characterized by an exaggerated oxidative stress (OS). However, molecular mechanisms underlying HA-related effects are still partially disclosed. With these aims, a cell model of RCT was established by exposing primary human tenocytes to H₂O₂ for up to 72 h. Four different HAs by molecular weight were administered to measure nitric oxide (NO) and OS, apoptosis, and collagen 1 expression. In parallel, the well-known antioxidant ascorbic acid was administered for comparison. The present study highlights that HAs characterized by a low molecular weight are able to counteract the H₂O₂-induced OS by decreasing the percentage of apoptotic cells and reversing the activation of caspase 3 and 7. Likewise, NO intracellular levels are comparable to the ones of controls. In parallel, collagen 1 expression was ameliorated by HAs characterized by higher molecular weights compared to AA. These findings confirm that HA plays an antioxidant role comparable to AA depending on the molecular weight, and highlight the molecular mechanisms underlying the HA anti-apoptotic effects. Full article

(This article belongs to the Special Issue The Interplay of Oxidative Stress and Inflammation: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

61 pages, 14169 KiB

Open AccessReview

The Pnictogen Bond, Together with Other Non-Covalent Interactions, in the Rational Design of One-, Two- and Three-Dimensional Organic-Inorganic Hybrid Metal Halide Perovskite Semiconducting Materials, and Beyond

by Arpita Varadwaj, Pradeep R. Varadwaj, Helder M. Marques and Koichi Yamashita

Int. J. Mol. Sci. 2022, 23(15), 8816; https://doi.org/10.3390/ijms23158816 - 8 Aug 2022

Cited by 16 | Viewed by 3246

Abstract

The pnictogen bond, a somewhat overlooked supramolecular chemical synthon known since the middle of the last century, is one of the promising types of non-covalent interactions yet to be fully understood by recognizing and exploiting its properties for the rational design of novel [...] Read more.

The pnictogen bond, a somewhat overlooked supramolecular chemical synthon known since the middle of the last century, is one of the promising types of non-covalent interactions yet to be fully understood by recognizing and exploiting its properties for the rational design of novel functional materials. Its bonding modes, energy profiles, vibrational structures and charge density topologies, among others, have yet to be comprehensively delineated, both theoretically and experimentally. In this overview, attention is largely centered on the nature of nitrogen-centered pnictogen bonds found in organic-inorganic hybrid metal halide perovskites and closely related structures deposited in the Cambridge Structural Database (CSD) and the Inorganic Chemistry Structural Database (ICSD). Focusing on well-characterized structures, it is shown that it is not merely charge-assisted hydrogen bonds that stabilize the inorganic frameworks, as widely assumed and well-documented, but simultaneously nitrogen-centered pnictogen bonding, and, depending on the atomic constituents of the organic cation, other non-covalent interactions such as halogen bonding and/or tetrel bonding, are also contributors to the stabilizing of a variety of materials in the solid state. We have shown that competition between pnictogen bonding and other interactions plays an important role in determining the tilting of the MX₆ (X = a halogen) octahedra of metal halide perovskites in one, two and three-dimensions. The pnictogen interactions are identified to be directional even in zero-dimensional crystals, a structural feature in many engineered ordered materials; hence an interplay between them and other non-covalent interactions drives the structure and the functional properties of perovskite materials and enabling their application in, for example, photovoltaics and optoelectronics. We have demonstrated that nitrogen in ammonium and its derivatives in many chemical systems acts as a pnictogen bond donor and contributes to conferring stability, and hence functionality, to crystalline perovskite systems. The significance of these non-covalent interactions should not be overlooked, especially when the focus is centered on the rationale design and discovery of such highly-valued materials. Full article

(This article belongs to the Collection Feature Papers in 'Physical Chemistry and Chemical Physics')

► Show Figures

Figure 1

19 pages, 3028 KiB

Open AccessArticle

Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice—A Pilot Study

by Ifigeneia Giakoumaki, Natalie Pollock, Turki Aljuaid, Anthony J. Sannicandro, Moussira Alameddine, Euan Owen, Ioanna Myrtziou, Susan E. Ozanne, Ioannis Kanakis, Katarzyna Goljanek-Whysall and Aphrodite Vasilaki

Int. J. Mol. Sci. 2022, 23(15), 8815; https://doi.org/10.3390/ijms23158815 - 8 Aug 2022

Cited by 4 | Viewed by 2971

Abstract

Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle [...] Read more.

Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood. Full article

(This article belongs to the Special Issue New Insights into the Epigenome and microRNAs in Musculoskeletal (Patho)physiology)

► Show Figures

Figure 1

27 pages, 2482 KiB

Open AccessReview

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

by Nina K. Popova, Anton S. Tsybko and Vladimir S. Naumenko

Int. J. Mol. Sci. 2022, 23(15), 8814; https://doi.org/10.3390/ijms23158814 - 8 Aug 2022

Cited by 31 | Viewed by 7260

Abstract

Being different multifactorial forms of psychopathology, aggression, depression and suicidal behavior, which is considered to be violent aggression directed against the self, have principal neurobiological links: preclinical and clinical evidence associates depression, aggression and suicidal behavior with dysregulation in central serotonergic (5-HT) neurotransmission. [...] Read more.

Being different multifactorial forms of psychopathology, aggression, depression and suicidal behavior, which is considered to be violent aggression directed against the self, have principal neurobiological links: preclinical and clinical evidence associates depression, aggression and suicidal behavior with dysregulation in central serotonergic (5-HT) neurotransmission. The implication of different types of 5-HT receptors in the genetic and epigenetic mechanisms of aggression, depression and suicidality has been well recognized. In this review, we consider and compare the orchestra of 5-HT receptors involved in these severe psychopathologies. Specifically, it concentrates on the role of 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₃ and 5-HT₇ receptors in the mechanisms underlying the predisposition to aggression, depression and suicidal behavior. The review provides converging lines of evidence that: (1) depression-related 5-HT receptors include those receptors with pro-depressive properties (5-HT_2A, 5-HT₃ and 5-HT₇) as well as those providing an antidepressant effect (5-HT_1A, 5-HT_1B, 5-HT_2C subtypes). (2) Aggression-related 5-HT receptors are identical to depression-related 5-HT receptors with the exception of 5-HT₇ receptors. Activation of 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2C receptors attenuate aggressiveness, whereas agonists of 5-HT₃ intensify aggressive behavior. Full article

(This article belongs to the Special Issue Brain Neurotransmitters in Genetic Control of Behavior 2.0)

► Show Figures

Figure 1

19 pages, 4826 KiB

Open AccessArticle

Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress–Mitochondrial Apoptotic and Autophagic Signaling Pathway

by Tsu-Jen Kuo, Yen-Hsuan Jean, Po-Chang Shih, Shu-Yu Cheng, Hsiao-Mei Kuo, Yi-Ting Lee, Yu-Cheng Lai, Chung-Chih Tseng, Wu-Fu Chen and Zhi-Hong Wen

Int. J. Mol. Sci. 2022, 23(15), 8813; https://doi.org/10.3390/ijms23158813 - 8 Aug 2022

Cited by 5 | Viewed by 2469

Abstract

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50–60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of [...] Read more.

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50–60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells. Full article

(This article belongs to the Section Molecular Oncology)

► Show Figures

Figure 1

41 pages, 3275 KiB

Open AccessReview

Forest Biomass as a Promising Source of Bioactive Essential Oil and Phenolic Compounds for Alzheimer’s Disease Therapy

by Patrícia Moreira, Patrícia Matos, Artur Figueirinha, Lígia Salgueiro, Maria Teresa Batista, Pedro Costa Branco, Maria Teresa Cruz and Cláudia Fragão Pereira

Int. J. Mol. Sci. 2022, 23(15), 8812; https://doi.org/10.3390/ijms23158812 - 8 Aug 2022

Cited by 2 | Viewed by 3402

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit [...] Read more.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-β (Aβ) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment. Full article

(This article belongs to the Section Molecular Biology)

► Show Figures

Figure 1

9 pages, 1235 KiB

Open AccessArticle

Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line

by Si-Yeon Kim, Jung-Ho Lee and Soon-Ae Kim

Int. J. Mol. Sci. 2022, 23(15), 8811; https://doi.org/10.3390/ijms23158811 - 8 Aug 2022

Cited by 5 | Viewed by 2228

Abstract

Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a [...] Read more.

Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, affects and alters autophagy activity. In cell viability assays, TPEN showed cytotoxicity in HT-22 cells. TPEN treatment also increased LC3-II levels and the ratio of LC3-II to LC3-I. Western blot analysis showed that phospho-AMP-activated protein kinase levels and the ratio of phospho-AMP-activated protein kinase to total AMP-activated protein kinase increased. Protein levels of the mammalian target of rapamycin and sirtuin 1 decreased following TPEN treatment. When TPEN-treated HT-22 cells were cotreated with autophagy inhibitors, 3-methyladenine (1 mM), or bafilomycin A1 (3 nM), the TPEN-induced decrease in cell viability was exacerbated. Cotreatment with chloroquine (10 μM) partially restored cell viability. The study showed that zinc deficiency induces autophagy and may be cytoprotective in neurons. We expect our results to add a new perspective to our understanding of the neuronal pathology related to zinc deficiency. Full article

(This article belongs to the Special Issue Autophagy in Cell Survival and Death)

► Show Figures

Figure 1

19 pages, 9310 KiB

Open AccessArticle

Accurate Determination of the Degree of Deacetylation of Chitosan Using UPLC–MS/MS

by Ting Xue, Wenqing Wang, Zhiyuan Yang, Fanjun Wang, Lei Yang, Jian Li, Hui Gan, Ruolan Gu, Zhuona Wu, Guifang Dou and Zhiyun Meng

Int. J. Mol. Sci. 2022, 23(15), 8810; https://doi.org/10.3390/ijms23158810 - 8 Aug 2022

Cited by 8 | Viewed by 2977

Abstract

The mole fraction of deacetylated monomeric units in chitosan (CS) molecules is referred to as CS’s degree of deacetylation (DD). In this study, 35 characteristic ions of CS were detected using liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS/MS). The relative response intensity of 35 characteristic [...] Read more.

The mole fraction of deacetylated monomeric units in chitosan (CS) molecules is referred to as CS’s degree of deacetylation (DD). In this study, 35 characteristic ions of CS were detected using liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS/MS). The relative response intensity of 35 characteristic ion pairs using a single charge in nine CS samples with varying DDs was analyzed using 30 analytical methods. There was a good linear relationship between the relative response intensity of the characteristic ion pairs determined using ultrahigh performance (UP) LC–MS/MS and the DD of CS. The UPLC–MS/MS method for determining the DD of CS was unaffected by the sample concentration. The detection instrument has a wide range of application parameters with different voltages, high temperatures, and gas flow conditions. This study established a detection method for the DD of CS with high sensitivity, fast analysis, accuracy, stability, and durability. Full article

(This article belongs to the Special Issue Chitosan: Structural and Chemical Modification, Properties and Application)

► Show Figures

Figure 1

16 pages, 5400 KiB

Open AccessArticle

Novel Antibiofilm Inhibitor Ginkgetin as an Antibacterial Synergist against Escherichia coli

by Yubin Bai, Weiwei Wang, Mengyan Shi, Xiaojuan Wei, Xuzheng Zhou, Bing Li and Jiyu Zhang

Int. J. Mol. Sci. 2022, 23(15), 8809; https://doi.org/10.3390/ijms23158809 - 8 Aug 2022

Cited by 15 | Viewed by 2782

Abstract

As an opportunistic pathogen, Escherichia coli (E. coli) forms biofilm that increases the virulence of bacteria and antibiotic resistance, posing a serious threat to human and animal health. Recently, ginkgetin (Gin) has been discovered to have antiinflammatory, antioxidant, and antitumor properties. In [...] Read more.

As an opportunistic pathogen, Escherichia coli (E. coli) forms biofilm that increases the virulence of bacteria and antibiotic resistance, posing a serious threat to human and animal health. Recently, ginkgetin (Gin) has been discovered to have antiinflammatory, antioxidant, and antitumor properties. In the present study, we evaluated the antibiofilm and antibacterial synergist of Gin against E. coli. Additionally, Alamar Blue assay combined with confocal laser scanning microscope (CLSM) and crystal violet (CV) staining was used to evaluate the effect of antibiofilm and antibacterial synergist against E. coli. Results showed that Gin reduces biofilm formation, exopolysaccharide (EPS) production, and motility against E. coli without limiting its growth and metabolic activity. Furthermore, we identified the inhibitory effect of Gin on AI-2 signaling molecule production, which showed apparent anti-quorum sensing (QS) properties. The qRT-PCR also indicated that Gin reduced the transcription of curli-related genes (csgA, csgD), flagella-formation genes (flhC, flhD, fliC, fliM), and QS-related genes (luxS, lsrB, lsrK, lsrR). Moreover, Gin showed obvious antibacterial synergism to overcome antibiotic resistance in E. coli with marketed antibiotics, including gentamicin, colistin B, and colistin E. These results suggested the potent antibiofilm and novel antibacterial synergist effect of Gin for treating E. coli infections. Full article

(This article belongs to the Special Issue Antivirulence Strategies to Overcome Antimicrobial Resistance)

► Show Figures

Figure 1

16 pages, 7960 KiB

Open AccessArticle

Transient and Prolonged Activation of Wnt Signaling Contribute Oppositely to the Pathogenesis of Asherman’s Syndrome

by Xiang Xue, Xiaoli Li, Jinmeng Yao, Xue Zhang, Xu Ren and Shan Xu

Int. J. Mol. Sci. 2022, 23(15), 8808; https://doi.org/10.3390/ijms23158808 - 8 Aug 2022

Cited by 2 | Viewed by 2230

Abstract

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the [...] Read more.

Asherman’s Syndrome (AS) is caused by dysfunction of endometrial regenerative ability, which is controlled by adult stem cells and their niche. The Wnt signaling pathway has been demonstrated to be implicated in this process. This study aimed to clarify the relationship between the Wnt signaling pathway and the progression of AS after initial endometrial damage. Endometria with and without adhesion as well as from the intrauterine devices three months after the surgery were collected to compare the area of fibrosis. The area% of fibrosis did not vary significantly. Significantly higher expression of non-phosphorylated β-catenin, Wnt5a and Wnt7a was identified in the endometria with adhesion. The CD140b⁺CD146⁺ endometrial stem-like cells were present in the endometria with adhesion. Both Wnt5a and Wnt7a promoted stem cell proliferation. However, only Wnt7a preserved stem cell population by stimulating self-renewal. A rat endometrial injury model was established to investigate the effect of the activated Wnt/β-catenin signaling pathway on endometrial healing. We found that a transient activation of the Wnt/β-catenin signaling pathway promoted angiogenesis and increased the number of glands. In conclusion, transient activation of the Wnt/β-catenin signaling pathway during the acute endometrial damage may help the tissue regeneration, while prolonged activation may correlate to fibrosis formation. Full article

(This article belongs to the Special Issue Molecular Research in Uterine Biology and Pathophysiology)

► Show Figures

Figure 1

12 pages, 8479 KiB

Open AccessArticle

Theoretical Design of a Janus-Nanoparticle-Based Sandwich Assay for Nucleic Acids

by Takumi Sato, Keiko Esashika, Eiji Yamamoto, Toshiharu Saiki and Noriyoshi Arai

Int. J. Mol. Sci. 2022, 23(15), 8807; https://doi.org/10.3390/ijms23158807 - 8 Aug 2022

Cited by 2 | Viewed by 1852

Abstract

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in [...] Read more.

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in the gap are crucial aspects of this strategy. Therefore, polymer-tethered nanoparticles (PTNPs), which show promise as high-performance materials that exhibit the attractive features of both NPs and polymers, were targeted in this study to achieve stable biomolecule sensing. Using coarse-grained molecular dynamics simulations, the dependence of the PTNP interactions on the length of the grafted polymer, graft density, and coverage ratio of a hydrophobic tether were examined. The results indicated that the smaller the tether length and graft density, the smaller was the distance between the PTNP surfaces (

R_{surf}

). In contrast,

R_{surf}

decreased as the coverage ratio of the hydrophobic surface (

ϕ

) increased. The sandwiching probability of the sensing target increased in proportion to the coverage ratio. At high

ϕ

values, the PTNPs aggregated into three or more particles, which hindered their sensing attributes. These results provide fundamental insight into the sensing applications of NPs and demonstrate the usefulness of PTNPs in sensing biomolecules. Full article

(This article belongs to the Special Issue 2nd Edition: Advances in Molecular Simulation)

► Show Figures

Figure 1

14 pages, 3270 KiB

Open AccessArticle

Neuroprotective Effect of Dexmedetomidine against Postoperative Cognitive Decline via NLRP3 Inflammasome Signaling Pathway

by Inja Cho, Bon-Nyeo Koo, So Yeon Kim, Sujung Park, Eun Jung Kim, Eun Hee Kam and Jeongmin Kim

Int. J. Mol. Sci. 2022, 23(15), 8806; https://doi.org/10.3390/ijms23158806 - 8 Aug 2022

Cited by 6 | Viewed by 2359

Abstract

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical [...] Read more.

Dexmedetomidine (Dex), widely used as a sedative in surgical procedures and intensive care units, induces sympatholytic, anxiolytic, analgesic, and sedative effects. Postoperative cognitive dysfunction (POCD) is routinely observed in postoperative care following surgery and general anesthesia. The NLRP3 inflammasome complex plays a critical role in innate immune response by detecting pathogenic microorganisms and activating pro-inflammatory cytokines. Although there are numerous protective effects of Dex among the neurological diseases, specific mechanisms including NLRP3 inflammasome-mediated neuroinflammation via oxidative stress response in a POCD model are not fully understood. Here, we investigated whether Dex exhibits neurocognitive effects through the NLRP3 inflammasome signaling in a POCD mouse model using a neurobehavioral test and ELISA analysis. We also confirmed the level of oxidative stress-related response in the in vitro system in the POCD model. Furthermore, we evaluated the NLRP3 inflammasome complex by immunoprecipitation analysis. In summary, the results of the present study indicated that Dex showed a neuroprotective effect in the POCD model by reducing oxidative stress response through NLRP3 inflammasome-mediated neuroinflammation. Full article

(This article belongs to the Section Molecular Neurobiology)

► Show Figures

Figure 1

26 pages, 1677 KiB

Open AccessReview

The Effects of Probiotics, Prebiotics and Synbiotics in Non-Alcoholic Fat Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review

by Rodrigo Zamignan Carpi, Sandra M. Barbalho, Katia Portero Sloan, Lucas Fornari Laurindo, Heron Fernando Gonzaga, Paulo Cesar Grippa, Tereza L. Menegucci Zutin, Raul J. S. Girio, Cláudia Sampaio Fonseca Repetti, Cláudia Rucco Penteado Detregiachi, Patrícia C. Santos Bueno, Eliana de Souza Bastos Mazuqueli Pereira, Ricardo de Alvares Goulart and Jesselina Francisco dos Santos Haber

Int. J. Mol. Sci. 2022, 23(15), 8805; https://doi.org/10.3390/ijms23158805 - 8 Aug 2022

Cited by 57 | Viewed by 6372

Abstract

Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and [...] Read more.

Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system. Full article

(This article belongs to the Special Issue Inflammatory and Metabolic Dysregulations in Chronic Liver and Pancreas Disorders)

► Show Figures

Figure 1

34 pages, 4801 KiB

Open AccessArticle

The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts

by Marta Gerasymchuk, Gregory Ian Robinson, Olga Kovalchuk and Igor Kovalchuk

Int. J. Mol. Sci. 2022, 23(15), 8804; https://doi.org/10.3390/ijms23158804 - 8 Aug 2022

Cited by 9 | Viewed by 3383

Abstract

Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin [...] Read more.

Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial. In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested. We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001). Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)

► Show Figures

Figure 1

15 pages, 2677 KiB

Open AccessArticle

A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System

by Loretta László, Hédi Maczelka, Tamás Takács, Anita Kurilla, Álmos Tilajka, László Buday, Virag Vas and Ágota Apáti

Int. J. Mol. Sci. 2022, 23(15), 8803; https://doi.org/10.3390/ijms23158803 - 8 Aug 2022

Cited by 3 | Viewed by 2462

Abstract

Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene (SH3PXD2b) cause a rare developmental disorder called [...] Read more.

Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene (SH3PXD2b) cause a rare developmental disorder called Frank-Ter Haar syndrome (FTHS), which leads to heart abnormalities, bone tissue defects, and reduced adiposity. We aimed to produce a human stem cell-based in vitro FTHS model system to study the effects of the loss of the Tks4 protein in different cell lineages and the accompanying effects on the cell signalome. To this end, we used CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated (Cas9)) to knock out the SH3PXD2b gene in the HUES9 human embryonic stem cell line (hESC), and we obtained stable homo- and heterozygous knock out clones for use in studying the potential regulatory roles of Tks4 protein in embryonic stem cell biology. Based on pluripotency marker measurements and spontaneous differentiation capacity assays, we concluded that the newly generated Tks4-KO HUES9 cells retained their embryonic stem cell characteristics. We propose that the Tks4-KO HUES9 cells could serve as a tool for further cell differentiation studies to investigate the involvement of Tks4 in the complex disorder FTHS. Moreover, we successfully differentiated all of the clones into mesenchymal stem cells (MSCs). The derived MSC cultures showed mesenchymal morphology and expressed MSC markers, although the expression levels of mesodermal and osteogenic marker genes were reduced, and several EMT (epithelial mesenchymal transition)-related features were altered in the Tks4-KO MSCs. Our results suggest that the loss of Tks4 leads to FTHS by altering cell lineage differentiation and cell maturation processes, rather than by regulating embryonic stem cell potential. Full article

(This article belongs to the Collection Feature Papers in Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Int. J. Mol. Sci., Volume 23, Issue 15 (August-1 2022) – 778 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI