-
Scientific Reports May 2024This study employs a combination of mathematical derivation and optimization technique to investigate the adsorption of drug molecules on nanocarriers. Specifically, the...
This study employs a combination of mathematical derivation and optimization technique to investigate the adsorption of drug molecules on nanocarriers. Specifically, the chemotherapy drugs, fluorouracil, proflavine, and methylene blue, are non-covalently bonded with either a flat graphene sheet or a spherical fullerene. Mathematical expressions for the interaction energy between an atom and graphene, as well as between an atom and fullerene, are derived. Subsequently, a discrete summation is evaluated for all atoms on the drug molecule utilizing the U-NSGA-III algorithm. The stable configurations' three-dimensional architectures are presented, accompanied by numerical values for crucial parameters. The results indicate that the nanocarrier's structure effectively accommodates the atoms on the drug's carbon planes. The three drug types' molecules disperse across the graphene surface, whereas only fluorouracil spreads on the surface; proflavine and methylene blue stack vertically to form a layer. Furthermore, all atomic positions of equilibrium configurations for all systems are obtained. This hybrid method, integrating analytical expressions and an optimization process, significantly reduces computational time, representing an initial step in studying the binding of drug molecules on nanocarriers.
Topics: Adsorption; Graphite; Methylene Blue; Fluorouracil; Drug Carriers; Models, Theoretical; Algorithms; Fullerenes; Carbon; Proflavine; Nanoparticles; Antibiotics, Antineoplastic; Antineoplastic Agents
PubMed: 38796555
DOI: 10.1038/s41598-024-62483-4 -
Plants (Basel, Switzerland) May 2024is an opportunistic pathogen that is especially dominant in people with cystic fibrosis; the drug resistance expressed by this pathogen and its capacity for adaptation...
is an opportunistic pathogen that is especially dominant in people with cystic fibrosis; the drug resistance expressed by this pathogen and its capacity for adaptation poses a significant challenge to its treatment and control, thereby increasing morbidity and mortality rates globally. In this sense, the search for new treatment alternatives is imminent today, with products of plant origin being an excellent alternative for use. The objective of this research was to evaluate the antibacterial and antibiofilm potential and to explore the possible effect of ethanolic extracts from the wood and bark of on the cell membrane. Microdilution assays showed the inhibition of bacterial growth by more than 50%, with the lowest concentration (62.5 μg/mL) of both extracts evaluated. Furthermore, we report the ability of both extracts to inhibit mature biofilms, with inhibition percentages between 48.4% and 93.7%. Intracellular material leakage experiments (260/280 nm), extracellular pH measurements, and fluorescence microscopy with acridine orange (AO) and ethidium bromide (EB) showed cell membrane damage. This indicates that the antibacterial action of ethanolic extracts of is associated with damage to the integrity of the cell membrane and consequent death of these pathogens. These results serve as a reference for future studies in establishing the mechanisms of action of these extracts.
PubMed: 38794482
DOI: 10.3390/plants13101412 -
Nature Communications May 2024Nanoscale electron transfer (ET) in solids is fundamental to the design of multifunctional nanomaterials, yet its process is not fully understood. Herein, through X-ray...
Nanoscale electron transfer (ET) in solids is fundamental to the design of multifunctional nanomaterials, yet its process is not fully understood. Herein, through X-ray crystallography, we directly observe solid-state ET via a crystal-to-crystal process. We first demonstrate the creation of a robust and flexible electron acceptor/acceptor (A/A) double-wall nanotube crystal ([(Zn)(L)(L)]) with a large window (0.90 nm × 0.92 nm) through the one-dimensional porous crystallization of heteroleptic Zn metallocycles ((Zn)(L)(L)) with two different acceptor ligands (2,7-bis((1-ethyl-1H-imidazol-2-yl)ethynyl)acridine (L) and 2,7-bis((1-ethyl-1H-imidazol-2-yl)ethynyl)acridin-9(10H)-one (L)) in a slow-oxidation-associated crystallization procedure. We then achieve the bottom-up construction of the electron donor incorporated-A/A nanotube crystal ([(D)⊂(Zn)(L)(L)]) through the subsequent absorption of electron donor guests (D = tetrathiafulvalene (TTF) and ferrocene (Fc)). Finally, we remove electrons from the electron donor guests inside the nanotube crystal through facile ET in the solid state to accumulate holes inside the nanotube crystal ([(D)⊂(Zn)(L)(L)]), where the solid-state ET process (D - e → D) is thus observed directly by X-ray crystallography.
PubMed: 38782903
DOI: 10.1038/s41467-024-48599-1 -
European Review For Medical and... May 2024The article "Inhibition effects of acridone on the growth of breast cancer cells in vivo", by Y.-F. Xia, H.-J. Chu, G.-F. Kuang, G.-J. Jiang, Y.-C. Che, published in Eur...
The article "Inhibition effects of acridone on the growth of breast cancer cells in vivo", by Y.-F. Xia, H.-J. Chu, G.-F. Kuang, G.-J. Jiang, Y.-C. Che, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2356-2363-DOI: 10.26355/eurrev_201804_14827-PMID: 29762857 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer regarding a possible overlap in Figure 2, the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The journal investigation revealed a duplication between Figures 2B and 2C. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. The authors have been informed about the journal's investigation but remained unresponsive. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14827.
Topics: Humans; Breast Neoplasms; Acridones; Female; Cell Proliferation; Animals; Antineoplastic Agents; Cell Line, Tumor; Mice
PubMed: 38766783
DOI: 10.26355/eurrev_202405_36201 -
Animal Reproduction 2024This study aimed to analyze the characteristics of the HSP70 gene and protein in spermatozoa of Bali bulls of different age groups and to examine its potential as a...
This study aimed to analyze the characteristics of the HSP70 gene and protein in spermatozoa of Bali bulls of different age groups and to examine its potential as a biomarker determining bull fertility. This study used frozen semen produced from six Bali bulls divided into two groups based on age (≤ 9 years and ≥ 12 years). Parameters of frozen semen quality analyzed included sperm motility and kinetics using computer-assisted semen analysis, sperm morphological defects using Diff-Quick staining, acrosome integrity using FITC-PNA staining, and DNA fragmentation using acridine orange staining. HSP70 gene expression characterization was analyzed using qRT-PCR, and HSP70 protein abundance was analyzed using enzyme immunoassays. Fertility field data were obtained by analyzing the percentage conception rate for each bull based on the artificial insemination service data contained in the Indonesian-integrated system of the National Animal Health Information System (iSIKHNAS). The results showed significant differences (P<0.05) in total and progressive motility, morphological defects of the neck and midpiece, and tail of sperm, and acrosome integrity between the age groups of Bali bulls. HSP70 gene expression and protein abundance showed no significant differences (P>0.05) in different age groups. HSP70 gene expression correlated with fertility rate (P<0.05). Age affected several semen quality parameters but did not affect HSP70 gene expression and protein abundance. The HSP70 gene molecule could be a biomarker that determines the fertility of Bali bulls.
PubMed: 38756622
DOI: 10.1590/1984-3143-AR2023-0048 -
BMC Pediatrics May 2024Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous...
BACKGROUND
Neonatal Escherichia coli (E coli) meningitis results in significant morbidity and mortality. We present a case of a premature infant with extensive central nervous system (CNS) injury from recurrent E coli infection and the non-traditional methods necessary to identify and clear the infection.
CASE PRESENTATION
The infant was transferred to our institution's pediatric intensive care unit (PICU) after recurrence of E coli CNS infection requiring neurosurgical intervention. He had been treated for early onset sepsis (EOS) with ampicillin and gentamicin for 10 days followed by rapid development of ampicillin-resistant E coli septic shock and meningitis after discontinuation of antibiotics. Sterility of the CNS was not confirmed at the end of 21 days of cefepime therapy and was subsequently followed by recurrent ampicillin-resistant E coli septic shock and CNS infection. Despite 6 weeks of appropriate therapy with sterility of CSF by traditional methods, he suffered from intractable seizures with worsening hydrocephalus. Transferred to our institution, he underwent endoscopic 3rd ventriculostomy with cyst fenestration revealing purulent fluid and significant pleocytosis. An additional 3 weeks of systemic and intraventricular antibiotics with cefepime and tobramycin were given but a significant CNS neutrophil-predominant pleocytosis persisted (average of ∼ 21,000 cells/mm). Repeated gram stains, cultures, polymerase chain reaction (PCR) testing, and metagenomic next generation sequencing (NGS) testing of CSF were negative for pathogens but acridine orange stain (AO) revealed numerous intact rod-shaped bacteria. After the addition of ciprofloxacin, sterility and resolution of CSF pleocytosis was finally achieved.
CONCLUSION
Neonatal E coli meningitis is a well-known entity but unlike other bacterial infections, it has not proven amenable to shorter, more narrow-spectrum antibiotic courses or limiting invasive procedures such as lumbar punctures. Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Infant, Premature; Infant, Premature, Diseases; Meningitis, Escherichia coli
PubMed: 38755556
DOI: 10.1186/s12887-024-04787-y -
Chemico-biological Interactions Jun 2024Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties suitable for a range of industrial applications such as chemical processing...
Ionic liquids (ILs) are a class of low melting point salts with physicochemical properties suitable for a range of industrial applications such as chemical processing and battery design. Major challenges to the wide-scale adoption of ILs in industry include their eco- and cytotoxic effects, however, this opens up the possibility of the use of ILs use as novel anticancer agents. Understanding the structural features that promote IL cytotoxicity is therefore important. Key structural features that can impact IL cytotoxicity include size and lipophilicity of the cationic head group. In this study, the cytotoxic effects of acridinium-based ILs containing relatively large tri- and tetracyclic cations were evaluated. It was found that 9-phenylacridinium-based ILs are potent cytotoxic agents that reduce the viability of human MDA-MB-231 breast cancer cells with IC concentrations in the nanomolar range. In mechanistic studies, it was found that unlike the pyridinium-based analogue, [CPy][I], acridinium-based ILs did not inhibit oxidative phosphorylation or induce reactive oxygen species formation, and may instead target other mitochondrial processes or components such as mitochondrial DNA.
Topics: Humans; Ionic Liquids; Acridines; Structure-Activity Relationship; Cell Line, Tumor; Reactive Oxygen Species; Cell Survival; Antineoplastic Agents; Oxidative Phosphorylation
PubMed: 38735455
DOI: 10.1016/j.cbi.2024.111042 -
Orthopaedic Surgery Jun 2024The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation...
OBJECTIVES
The micro-nano structure of 3D-printed porous titanium (Ti) alloy with excellent performance in avoiding stress shielding and promoting bone tissue differentiation provides a new opportunity for the development of bone implants, but it necessitates higher requirements for bone tissue differentiation and the antibacterial properties of bone implants in clinical practice.
METHODS
This study investigated the preparation, antimicrobial properties, and osteogenesis-promoting ability of the 3D printed porous Ti alloy anodic oxidized Ag-carrying (Ag@3D-TiO) scaffolds. The 3D printed porous Ti alloy (3D-Ti), anodized 3D printed porous Ti alloy (3D-TiO), and Ag@3D-TiO scaffolds were synthesized using electron beam melting. The antimicrobial properties of the scaffolds were examined using antibacterial tests and their cytocompatibility was assessed using a cell proliferation assay and acridine orange/ethidium bromide (AO/EB) staining. In vitro cellular assays were used to investigate the effects of the scaffold microstructural features on cell activity, proliferation, and osteogenesis-related genes and proteins. In vivo animal experiments were used to evaluate the anti-inflammatory and osteogenesis-promoting abilities of the scaffolds.
RESULTS
The Ag@3D-TiO scaffolds exhibited sustained anti-microbial activity over time, enhanced cell proliferation, facilitated osteogenic differentiation, and increased extracellular matrix mineralization. In addition, alkaline phosphatase (ALP), collagen type I (COL-I), and osteocalcin (OCN)-related genes and proteins were upregulated. In vivo animal implantation experiments, the anti-inflammatory effect of the Ag@3D-TiO scaffolds were observed using histology, and a large amount of fibrous connective tissue was present around it; the Ag@3D-TiO scaffolds were more bio-compatible with the surrounding tissues compared with 3D-Ti and 3D-TiO; a large amount of uniformly distributed neoplastic bone tissue existed in their pores, and the chronic systemic toxicity test showed that the 3D-Ti, 3D-TiO, and Ag@3D-TiO scaffolds are biologically safe.
CONCLUSION
The goal of this study was to create a scaffold that exhibits antimicrobial properties and can aid bone growth, making it highly suitable for use in bone tissue engineering.
Topics: Titanium; Osteogenesis; Tissue Scaffolds; Silver; Animals; Printing, Three-Dimensional; Mice; Cell Proliferation; Cell Differentiation; Anti-Bacterial Agents; Porosity
PubMed: 38706035
DOI: 10.1111/os.14081 -
Poultry Science Jun 2024Sertoli cells (SC) are a type of important cells in the testes, which can provide transport proteins, regulatory proteins, growth factors, and other cytokines for the...
Sertoli cells (SC) are a type of important cells in the testes, which can provide transport proteins, regulatory proteins, growth factors, and other cytokines for the spermatogenic process. They participate in the regulation of the maturation and differentiation of spermatogenic cells and play an important supporting role in the migration, proliferation, and differentiation of germ cells at all levels in the testes. Previous studies found differential expression of LINC9137, miR-140-3p, and Sodium/Potassium Transporting ATPase Interacting 3 (NKAIN3) genesin high and low sperm motility goose testicular tissues. This study investigated the effects of the LINC9137-miR-140-3p-NKAIN3 signal axis on the proliferation and apoptosis of goose testicular sertoli cells at the cellular level, respectively. The results showed that through acridine orange staining, oil red O staining, Alkaline phosphatase (AKP) staining, and RT qPCR assay, it was comprehensively identified that the cultured testicular sertoli cells were purified in vitro. Through the dual luciferase activity detection test, it was found that LINC9137 has a targeted binding site with miR-140-3p and NKAIN3. In addition, this study found that overexpression of miR-140-3p significantly inhibited the expression of LINC9137 and NKAIN3 in sertoli cells, and their expression was significantly increased when miR-140-3p was interfered with. By measuring cell proliferation activity and apoptosis related gene expression, it was found that overexpression of LINC9137 decreased cell proliferation activity (P > 0.05), while the expression level of apoptosis factor Bcl2 Associated X Protein (Bax)/B-cell lymphoma-2 (Bcl2) increased (P > 0.05). On the contrary, when interfering with LINC9137, the cell proliferation activity of sertoli cells was significantly increased (P < 0.01), and the expression level of apoptosis factor Bax/Bcl2 was significantly reduced (P < 0.05); The effect of miR-140-3p on the proliferation and apoptosis of sertoli cells is opposite to that of LINC9137. Meanwhile, this study co transfected overexpressed LINC9137 and miR-140-3p plasmids into sertoli cells, and found that the effect of LINC9137 overexpression on supporting cell proliferation was weakened by miR-140-3p. This study elucidates the role and function of the LINC9137 miR-140-3p-NKAIN3 signaling axis in the development of goose testes and spermatogenesis, establishes a regulatory network related to spermatogenesis, and provides a theoretical basis for studying the genetic regulation of goose spermatogenesis.
Topics: Animals; Male; Sertoli Cells; MicroRNAs; Signal Transduction; Geese; Avian Proteins; Apoptosis; Testis; Cell Proliferation; RNA, Long Noncoding
PubMed: 38701630
DOI: 10.1016/j.psj.2024.103724 -
Molecules (Basel, Switzerland) Apr 2024Alzheimer's disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling...
Alzheimer's disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (, AChE: IC = 0.223 μM) with pyrimidone compound (GSK-3: IC = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound possessed potent dual AChE/GSK-3 inhibition (AChE: IC = 0.047 ± 0.002 μM, GSK-3: IC = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure-activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs.
Topics: Alzheimer Disease; Humans; Cholinesterase Inhibitors; Acetylcholinesterase; Molecular Docking Simulation; Drug Design; Glycogen Synthase Kinase 3 beta; Cell Line, Tumor; Sulfur; Structure-Activity Relationship; Acridines; Tacrine; Molecular Structure
PubMed: 38675602
DOI: 10.3390/molecules29081782