DMSO Research Articles

A Novel Aliphatic Ketone‐Based Solid Polymer Electrolyte with High Salt‐Soluble Ability Enabling Highly Stable Lithium‐Metal Batteries

AbstractLow room temperature ionic conductivity and interfacial incompatibility are the key factors that hinder the practical application of solid polymer electrolyte (SPEs) in lithium metal batteries. Increasing the ability of the SPEs to dissolve and dissociate lithium salt is helpful to enhance ion transport capacity of the SPEs. Herein, ketone groups with high solubility and dissociation ability of lithium salt are introduced into the structural design of SPE, an aliphatic ketone solid polymer electrolyte (KT@SPE) with crosslinking structure is prepared by ultraviolet (UV) polymerization. The prepared KT@SPE shows excellent viscoelastic and possess room temperature ionic conductivity of 10−4 S cm−1 with 200 wt% lithium bis((trifluoromethyl)sulfonyl)azanide (LiTFSI). Thanks to the contribution of high ion transport capacity, construction of multi‐hydrogen bonds network structure of KT@SPE and a wettability of controlling residual dimethyl sulfoxide (DMSO) solvent to the interface, the assembled symmetrical Li cell realizes stable cycling for over 2000 h at 0.15 mA cm−2. Moreover, LiFePO4 cell achieves stable long cycle at 5C and enable Li/KT@SPE3/LiFe0.6Mn0.4PO4 cell operates at 4.4 V. This work not only provides a design strategy for preparing novel solid polymer electrolytes, but also exhibits the excellent application potential of aliphatic ketone‐based polymer electrolyte in solid‐state lithium batteries at high current density and high voltage.

Quantification of diclofenac in natural waters by the photo-induced fluorescence (PIF) method

A photo-induced fluorescence (PIF) method was developed for the quantification of diclofenac sodium, sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate (NaDCF), in natural waters. Since diclofenac is not naturally fluorescent, its photoconversion under UV irradiation was carried out to produce highly fluorescent photoproduct(s) in various media (water, methanol, isopropanol, acetonitrile, ethyl acetate, dimethyl sulfoxide (DMSO), and a water-isopropanol mixture). The photoproduct responsible for the intense fluorescence of NaDCF in aqueous media was identified as chloro-carbazole by gas chromatography-mass spectrometry (GC-MS). Several PIF parameters were optimized. Using the PIF method, a highly fluorescent diclofenac photoproduct was obtained at λex/λem = 235/360 nm, with optimum fluorescence achieved after 10 min irradiation in a water-isopropanol mixture (90:10 v/v). The limit of detection (LOD) and quantification (LOQ) for diclofenac sodium in this medium were 0.11 ng ml–1 and 0.37 ng ml–1, respectively, with low relative standard deviation (RSD) values. The PIF calibration curves demonstrated good linearity, extending over one to three orders of magnitude, with correlation coefficients (R2) near unity, indicating good reproducibility. Analytical applications of this method to natural water samples yielded satisfactory results, with average recovery rates ranging from 84.77 to 101.72 %.

Aspects of the Clinical use of the Import-Substituted Radiopharmaceutical Agent 18F-PSMA in Prostate Cancer

One of the most common types of radionuclide studies, which are gaining traction in oncology, is positron emission tomography combined with computed tomography. The most significant and promising radiopharmaceutical agent in the radionuclide diagnosis of prostate cancer is 18F-PSMA. A high sensitivity and specificity of this radiopharmaceutical agent for prostate cancer are due to the prostate-specific membrane antigen, which is the second type of transmembrane glycoprotein with a high expression in endothelial cells during neoangiogenesis. The purpose is to develop a domestic import–substituted radiopharmaceutical agent 18F-PSMA, manufactured in the system of the Federal Medical and Biological Agency of Russia using domestic substances and excipients. Materials and methods. The syntheses were carried out on the Fastlab GE Healthcare module. This module has been repeatedly used to manufacture the radiopharmaceutical agent 18F-PSMA-1007 using original ABX cassettes. The reagent kit consisted of a vial with the precursor 18F-PSMA-1007, a vial with dimethyl sulfoxide for dissolving the precursor, and a vial with a solution of tetrabutylammonium in ethanol. Additional vials used outside the cassette and connected by connecting tubes with needles contained ethanol solutions with concentrations of 5 and 30%, a phosphate buffer solution. A QMA (quaternary methylamonium) cartridge was used to isolate fluorine-18. Sequentially connected PS-H+ and C18 extraction cartridges were used to isolate and purify the final product. Consumables included a «skeleton» with rotary valves, a housing, a three-necked reactor flask, glass vials, connecting tubes and adapters. Results. The process of synthesizing a radiopharmaceutical agent using domestic reagents was similar to the original one. A comparative analysis of the synthesis charts, a comparative analysis of the activity and yield of RFP made from domestic and imported reagents, and an assessment of radiochemical purity were carried out. The physiological and pathological distribution of the domestic radiopharmaceutical agent, as well as its comparison to the original drug, were carried out in the clinical part of the study, during which no side effects and adverse events were noted in patients. Conclusions. The radiopharmaceutical preparation made from domestic reagents using adapted technology for the original cassette is identical to the original in all quality indicators and corresponds to approved regulatory values.

Trehalose Cryopreservation of Human Mesenchymal Stem Cells from Cord Tissue.

Adequate hypothermic storage of human mesenchymal stem cells (hMSCs) is of fundamental importance since they have been explored in several regenerative medicine initiatives. However, the actual clinical application of hMSCs necessitates hypothermic storage for long periods, a process that requires the use of non-toxic and efficient cryo-reagents capable of maintaining high viability and differentiating properties after thawing. Current cryopreservation methods are based on cryoprotectant agents (CPAs) containing dimethylsulphoxide (DMSO), which have been shown to be toxic for clinical applications. In this study, we describe a simple and effective trehalose (TRE)-based solution to cryo-store human umbilical cord-derived MSCs (UC-MSCs) in liquid nitrogen. Cells viability, identity, chromosomal stability, proliferative and migration capacity, and stress response were assessed after cryopreservation in TRE as CPA, testing different concentrations by itself or in combination with ethylene glycol (EG). Here we show that TRE-stored UC-MSCs provided lower cell recovery rates compared with DMSO-based solution, but maintained good functional properties, stability, and differentiating potential. The best cell recovery was obtained using 0.5 M TRE with 10% EG showing no differences in the osteogenic, adipogenic, and chondrogenic differentiation capacity. A second cycle of cryopreservation in this TRE-based solution had no additional impact on the viability and morphology, although slightly affected cell migration. Furthermore, the expression of the stress-related genes, HSPA1A, SOD2, TP53, BCL-2, and BAX, did not show a higher response in UC-MSCs cryopreserved in 0.5 M TRE + 10% EG compared with DMSO. Together these results, in addition to ascertained therapeutic properties of TRE, provide sufficient evidence to consider TRE-based medium as a low-cost and efficient solution for the storage of human UC-MSCs cells and potentially substitute DMSO-based cryo-reagents.

Na+-Complexed Dendritic Polyglycerols for Recovery of Frozen Cells and Their Network in Media.

In this study, a novel phenomenon is identified where precise control of topology and generation of polyglycerol induce the retention of Na+ ions in biological buffer systems, effectively inhibiting ice crystal growth during cryopreservation. Unlike linear and hyperbranched counterparts, densely-packed hydroxyl and ether groups in 4th-generation dendritic polyglycerol interact with the ions, activating the formation of hydrogen bonding at the ice interface. By inhibiting both intra- and extracellular ice growth and recrystallization, this biocompatible dendritic polyglycerol proves highly effective as a cryoprotectant; hence, achieving the cell recovery rates of ≈134-147%, relative to those of 10% dimethyl sulfoxide, which is a conventional cryoprotectant for human tongue squamous carcinoma (HSC-3) cell line and human umbilical vein endothelial (HUVEC) cells. Further, it successfully recovers the network-forming capabilities of HUVEC cells to ≈89% in tube formation after thawing. The Na+ ion retention-driven ice-growth inhibition activity in biological media highlights the unique properties of dendritic polyglycerol and introduces a new topological concept for cell-cryoprotectant development.

ПОЛУЧЕНИЕ И КОМПЛЕКСНАЯ ОЦЕНКА ДИАГНОСТИЧЕСКИХ СЫВОРОТОК К АНТИГЕНУ YERSINIA PSEUDOTUBERCULOSIS,ВЫДЕЛЕННОМУ С ПРИМЕНЕНИЕМ ДИМЕТИЛСУЛЬФОКСИДА

The aim of the study is to obtain hyperimmune blood sera of guinea pig and rabbit using an antigen isolated from Yersinia pseudotuberculosis cells using dimethyl sulfoxide, as well as to study the possibility of complex use of the obtained specific antibodies in indirect enzyme immunoassay (ELISA) for the detection of Yersinia. To obtain hyperimmune sera, a mixture of antigen and adjuvant was used in a ratio of 1:1. Proteins predominated in the composition of the antigen. It was administered to animals in the amount of 0.6 mg per guinea pig and 2 mg per rabbit. 1 % polyazolidinammonium modified with iodine hydrate ions was used as an adjuvant. Animals were immunized subcutaneously five times with an interval of 2 weeks. The resulting sera showed generic specificity in ELISA against Yersinia enterocolitica and Yersinia pseudotuberculosis (1:6400–1:25600). Their interaction with Escherichia coli, Salmonella typhimurium, Proteus vulgaris, Enterobacter aerogenes, Brucella abortus was insignificant (1:100–1:400). The complex use of specific hyperimmune blood sera from two animal species made it possible to conduct indirect ELISA for antigen detection. To do this, we adsorbed guinea pig antibodies on the surface of microplate wells. Then, with the help of rabbit serum, an indication of the antigen attached to the guinea pig antibodies adsorbed on the microplate was carried out. Rabbit antibodies were detected with a peroxidase antispecies conjugate. The complex use of experimental sera made it possible to detect enteropathogenic Yersinia in the accumulation medium even under conditions of significant fecal contamination of the test material already on the 3rd day of “cold enrichment”, provided that at least 50 Yersinia cells were added to 1 ml of the accumulation medium.

The Phytochemical and Biological Activities of Two <i>Phyllanthus </i>Species: Insights into Metabolit, Antioxidant and Antibacterial Activity

Phylanthus species, including P. niruri and P. urinaria have pharmacological potential due to their rich phytochemical composition. People usually used this plant for medicinal treatments. This study aimed to compare the phytochemical and antioxidant and antibacterial activities of two Phyllanthus species. The whole of plants was extracted using maceration method with ethanol as solvent. Phytochemical content analyzed using spectrophotometer. The reagent used for each compounds that were Folin-ciocalteu for phenolics, AlCl3 for flavonoid, dimethyl sulfoxide for chlorophyll and carotenoid. Bioactivity analysis using 1,1-diphenyl-2-picrylhydrazyl method for antioxidant activity and Kirby-Bauer method for antibacterial activity. The highest flavonoid content (12.22 mg QE/gram extract) and total chlorophyll (43.2 µg/ml extract) in P. niruri while phenolic content (80.8 mg GAE/gram extract) in P. urinaria. The carotene of both Phyllanthus were similar (11.9 µg/ml extract. The IC50 values of P. urinaria (6.16 ± 0.42 μg/ml) and P. niruri (17.72 ± 0.80 μg/ml), which indicated very strong antioxidant activity. P. urinaria leaf extract had stronger inhibition against Escherichia coli than Staphylococcus aureus (>20 mm) and P. niruri leaf extract could inhibit E. coli and S. aureus bacteria at all concentrations (11-20 mm). This study found that phenolic compounds strongly influenced the antioxidant and antibacterial abilities of Phyllanthus, while chlorophyll and carotenoids had only a slight influence. These findings open up opportunities to utilize P. niruri and P. urinaria as antioxidant and antibacterial agents.

STUDIES ON THE COMPLEXES OF ISONICOTINOYL 2-CHLOROBENZALDEHYDE HYDRAZONES WITH CU II AND MN II AND THEIR ANTIMICROBIAL STUDIES

Complexes isonicotinoyl 2-chlorobenzaldehyde hydrazone with Mn II and Cu II were synthesized and characterized using UV visible spectrophotometry, Infrared spectrophotometry Atomic Absorption Spectrophotometry, melting point, solubility test, conductivity measurement, magnetic susceptibility. Some bacterial and fungal strains were used to screen for the biological activities of the ligands and complexes. The melting point of the ligand (216 – 218) °C is higher than 106 – 107.80C of the Mn complex. The Cu complex decomposed at 174°C.The solubility showed that the ligand and complexes were soluble in dimethyl sulphoxide, but insoluble in water. The conductivity test showed that the Cu complex are conductors with higher value (9.934) µS/cm, while the Mn complexes are non-conductor with lower value (1.346) µS/cm. The magnetic susceptibility measurement pointed out that the complexes are paramagnetic with unpaired electrons. There was coordination via the azomethine nitrogen and carbonyl oxygen in all the complexes with a square planar geometries stoichiometrically combined in the ratio of ML 1:2 for the metal and ligand respectively. The ligand and complexes showed appreciable activities against Methicillin resistant staphlococus aureus (MRSA), Escherichia coli, Helicobacter pylori, salmonella typhi Aspergillus fumigatus and aspergillus niger

Stepwise Modulation of Bridged Single-Benzene-Based Fluorophores for Materials Science.

In recent years, researchers studying fluorogenic samples have steadily shifted from using large, expensive, poorly soluble fluorophores with complex synthetic sequences to smaller, simpler p scaffolds with low molecular weight. This research article presents an in-depth study of the photophysical properties of five bridged single-benzene-based fluorophores (SBBFs) investigated for their solution and solid-state emission (SSSE) properties. The compounds O4, N1O3, N2O2, N3O1, and N4 are derived from a central terephthalonitrile core and vary in the amount of oxygen and nitrogen bridging atoms. These minimalized emitters show full-color tunable emission properties and exhibit moderate-to-high photoluminescence quantum yield values reaching up to 0.78 in dimethyl sulfoxide (DMSO). In addition to demonstrating excellent compatibility in poly(methyl methacrylate) (PMMA) films and additive manufacturing using stereolithography (SLA), white light emission was achieved in both solution and 3D-printed materials by controlling the mixing ratio of the compounds. Employing density-functional theory (DFT), well-correlating theoretical absorption and emission wavelengths were calculated as average values of the different possible conformers. Furthermore, cellular internalization of the substances was accomplished using Pluronic® F-127 nanoparticles. Overall, this study emphasizes the remarkable properties of single-benzene-based emitters, showcasing their accessibility and potential applications in biomedical fields and materials science.

Reaction of 4-(Alkynyloxy)cyclohexa-2,5-dienones with Dimethyl Sulfoxide: A Catalyst-Free Formation of 6/5/3-Fused Tricyclic Enones.

6/5/3-Fused tricyclic enones were obtained when 4-(alkynyloxy)cyclohexa-2,5-dienones were treated with DMSO at 150 °C. The reaction proceeded via a four-membered oxathietene intermediate. The protocol developed is atom economical, has a broad substrate scope, and is amenable to gram-scale synthesis. The products obtained are susceptible to further synthetic transformations.

Ordered Aggregates of Fmoc-Diphenylalanine at Alkaline pH as a Precursor of Fibril Formation and Peptide Gelation.

The ultrashort peptide N-fluorenylmethoxycarbonyl-phenylalanyl-phenylalanine (FmocFF) has been largely investigated due to its ability to self-assemble into fibrils (100 nm-μm scale) that can form a sample-spanning gel network. The initiation of the gelation process requires either a solvent switch (water added to dimethyl sulfoxide) or a pH-switch (alkaline to neutral) protocol, both of which ensure the solubility of the peptide as a necessary step preceding gelation. While the respective gel phases are well understood in structural and material characteristics terms the pregelation conditions are known to a lesser extent. The question we asked is to what extent the gel-forming fibrils are already partially formed, i.e., oligomers or protofibrils. Focusing on the pregelation conditions for the pH-switch method, we investigated the self-assembly of soluble FmocFF aggregates in alkaline pH by UV circular dichroism, IR, vibrational circular dichroism, and 1H NMR spectroscopy for different peptide concentrations and more systematically as a function of temperature. The temperature dependence of the UVCD spectra of FmocFF in H2O and D2O revealed a complicated isotope effect that affects the peptide backbone and fluorene conformations in peptide aggregates differently. Moreover, we found that the melting of formed aggregates depends on peptide concentration in a nonmonotonic way. At 20 mM the UVCD data revealed the population of at least two different thermodynamic intermediate states, which seem to differ in terms of the relative arrangement of the fluorene moiety. The IR spectrum of this sample at room temperature indicates an antiparallel β-sheet arrangement, as suggested earlier in the literature. However, we show that this interpretation can only be valid if one invokes a nondispersive redshift of the two amide I' bands in a locally crystalline environment. The respective vibrational circular dichroism spectrum of the amide I' region is consistent with a left-handed helically twisted structure of the formed aggregates. A comparison of our data with spectra of the aqueous gel phase suggests that fibrils in the latter resemble the ones at alkaline pH probed by our experiments.

Doping Control Analysis of Methylsulfonylmethane in Horses.

Methylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur-containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti-inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination of DMSO in horses has been reported; however, there has been no report on the elimination of MSM in horses. This paper describes a pilot study of an administration study of MSM in two geldings following one scoop (~15 g) of Pure MSM twice daily for six consecutive days. MSM in post-administration urine and blood samples was quantified by gas chromatography-mass spectrometry after sample dilution, with additional protein precipitation for the blood samples. The elimination profiles of MSM in urine and blood are described. The maximum detection time in urine at the IRL of 1200 μg/mL was around 4.5 days after the last dose. Plasma MSM in both horses was around 120 μg/mL at 4.4 days after the last dose, which was the last blood sample collected. As such, 120 μg/mL may indicate a possible IRL for controlling MSM in horse blood. The analysis of DMSO in post-MSM-administration samples showed that DMSO is not a significant metabolite of MSM in horses.

Synthesis of 2-Amino-quinazolin-4(3H)-ones Using 2-Bromo-N-phenylbenzamide and Cyanamide Ullmann Cross-Coupling.

Herein, an approach for synthesizing 2-amino-3-substituted quinoline-4(3H)-ones and N-phenylbenzamide derivatives was developed. A series of quinoline-4(3H)-ones were synthesized through Ullmann cross-coupling under air conditions using inexpensive, readily available cyanamide with 2-bromo-N-phenylbenzamide as the starting material, copper iodide as the catalyst, and potassium tert-butoxide as the base in dimethyl sulfoxide. Noteworthy aspects of this method include its cost-effectiveness, the accessibility of raw materials, wide substrate applicability, ligand-free, open-air conditions, and simple operating procedures. Furthermore, investigations under similar reaction conditions further show that substituting water, alcohols, phenols, amines, or mercaptans for cyanamide as the nucleophilic reagent can be used to prepare 2-functionalized N-phenylbenzamides.

Application of Saccharide Cryoprotectants in the Freezing or Lyophilization Process of Lipid Nanoparticles Encapsulating Gene Drugs for Regenerative Medicine

Article Application of Saccharide Cryoprotectants in the Freezing or Lyophilization Process of Lipid Nanoparticles Encapsulating Gene Drugs for Regenerative Medicine Wanqi Li 1,†, Ting Wang 1,†, Jianyang Chen 1, Minmei Guo 1, Ling Ling 1 and Akon Higuchi 1,2,3,* 1 State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan Road, Wenzhou 325027, China 2 Department of Chemical and Materials Engineering, National Central University, No. 300, Jhongda RD., Jhongli District, Taoyuan 32001, Taiwan 3 R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli District, Taoyuan 32023, Taiwan * Correspondence: higuchi@ncu.edu.tw or higuchi@wmu.edu.cn † These authors contributed equally to this work. Received: 14 November 2024; Revised: 15 December 2024; Accepted: 16 December 2024; Published: 20 December 2024 Abstract: Lipid nanoparticles (LNPs) have emerged as highly efficient drug delivery systems in gene therapy and regenerative medicine and have demonstrated great potential in recent years. Notably, LNPs encapsulating mRNA vaccines have achieved remarkable success in combating the COVID-19 epidemic. However, LNPs encapsulating mRNA encounter issues of physical and chemical instability and need to be stored and transported under harsh conditions. Lyophilization technology, which is commonly used to increase the stability of nanomedicines, has been increasingly applied to stabilize mRNA-LNPs. Appropriate cryoprotectants, such as saccharides, glycerin, and dimethyl sulfoxide (DMSO), need to be added to mRNA-LNPs during the freezing or lyophilization process to effectively preserve the physical and chemical properties of mRNA-LNPs, ensuring their stability. Saccharides (i.e., sucrose, trehalose, and maltose) are the most widely used cryoprotectants to protect the integrity of mRNA-LNPs. This is because saccharides are relatively safe molecules compared with other chemical molecules for cells and animals. However, different saccharides have varying levels of protective effects on mRNA-LNP formulations, and the optimal saccharide concentration varies depending on the specific mRNA-LNP. This article reviews the application and mechanisms of saccharide-based cryoprotectants in the freezing or lyophilization process of LNP-delivered gene therapies and regenerative medicines, offering guidance for selecting the most appropriate saccharide-based cryoprotectants for mRNA-LNP drugs during freezing or lyophilization processes.

TPD-seq: A high throughput RNA-seq method to derive transcriptomic points of departure from cell lines.

There is growing scientific and regulatory interest in transcriptomic points of departure (tPOD) values from high-throughput in vitro experiments. To further help democratize tPOD research, here we outline 'TPD-seq' which links microplate-based exposure methods involving cell lines for human (Caco-2, Hep G2) and environmental (rainbow trout RTgill-W1) health, with a commercially available RNA-seq kit, with a cloud-based bioinformatics tool (ExpressAnalyst.ca). We applied the TPD-seq workflow to derive tPODs for solvents (dimethyl sulfoxide, DMSO; methanol) and positive controls (3,4-dichloroaniline, DCA; hydrogen peroxide, H2O2) commonly used in toxicity testing. The majority of reads mapped to protein coding genes (~9 k for fish cells; ~6 k for human cells), and about 50 % of differentially expressed genes were curve-fitted from which 90 % yielded gene benchmark doses. The most robust transcriptomic responses were caused by DMSO exposure, and tPOD values were 31-155 mM across the cell lines. OECD test guideline 249 (RTgill-W1 cells) recommends the use of DCA and here we calculated a tPOD of ~5 to 76 μM. Finally, exposure of the two human cell lines to H2O2 resulted in tPOD values that ranged from 0.7 to 1.1 mM in Caco-2 cells and 5-30 μM in Hep G2 cells. The methods outlined here are designed to be performed in laboratories with basic molecular and cell culture facilities, and the performance and scalability of the TPD-seq workflow can be determined with additional case studies.

Osteogenesis and Embryogenesis in Zebrafish Embryo Is Differentially Modulated by Solvents and Prednisolone

Several molecules and extracts are known to have bone-specific effects. For example, the long-term use of glucocorticoids like prednisolone causes several negative effects including a loss of bone mass. Molecules like prednisolone are usually dissolved in organic solvent which are known to be toxic for zebrafish embryo in certain concentrations. Nevertheless, solvents like dimethyl sulfoxide (DMSO), ethanol and methanol have never been tested for specific skeletal effects during development in dose-dependency. Vitality assay, live fluorescence and bone-specific staining were used to evaluate solvents effects compared to prednisolone. DMSO, ethanol and methanol perturb osteogenesis starting from 1%, 1.5% and 3% respectively, concentrations in which vasculature, length and survival rate appear unaffected. This effect may be due to high sensitivity of the osteogenesis process to external chemical stimuli, especially in the trunk. On the contrary, the negative effect of prednisolone on skeletal development appears more specific since it is found at very low concentrations, far from any other developmental defects. The recommended solvent concentration to be used in zebrafish embryos osteogenesis assay was established in 0.5% for DMSO, 2% for methanol and 0.5% for ethanol. We recommend analyzing both head and trunk mineralization in zebrafish embryo osteogenesis assay.

LAT4 drives temozolomide induced radiotherapy resistance in glioblastoma by enhancing mTOR pathway activation

BackgroundGlioblastoma multiforme (GBM) represents the most prevalent form of primary malignant tumor within the central nervous system. The emergence of resistance to radiotherapy and chemotherapy represents a significant impediment to advancements in glioma treatment.MethodsWe established temozolomide (TMZ)-resistant GBM cell lines by chronically exposing U87MG cell lines to TMZ, and dimethyl sulfoxide (DMSO) was used as placebo control. In vivo and in vitro experiments verified the resistance of resistant cells to chemotherapy and radiotherapy. LAT4 was identified by transcriptomics to be associated with GBM treatment resistance and relapse. The relationship between LAT4 and mTOR pathway activity was also analyzed. Finally, the effect of BCH (LAT inhibitor) combined with radiotherapy on GBM prognosis was verified in vivo.ResultsWe have first confirmed that TMZ not only induces resistance to chemotherapy in GBM cells but also enhances their resistance to radiotherapy, which is a significant finding in the process of building TMZ-resistant U87MG GBM cell lines. We then performed comprehensive transcriptomic analysis and identified amino acid metabolism as a potential key factor in radiotherapy resistance. Specifically, we confirmed that the upregulation of LAT4 following chemotherapy enhances leucine metabolism within tumors in vitro and in vivo, thereby modulating the mechanistic target of mTOR pathway and leading to radiotherapy resistance. Of note, the application of inhibitors targeting leucine metabolism was shown to restore the sensitivity of these cells to radiotherapy, highlighting a potential therapeutic strategy for overcoming resistance in GBM.ConclusionsOur study links tumor sensitivity to chemotherapy and radiotherapy and highlights the critical role of LAT4 in activating the mTOR pathway and GBM radiotherapy resistance. It suggests ways to improve radiotherapy sensitivity to GBM.

Paracentrotus lividus sea urchin gonadal extract mitigates neurotoxicity and inflammatory signaling in a rat model of Parkinson's disease.

The present study investigates the neuroprotective effects of the sea urchin Paracentrotus lividus gonadal extract on rotenone-induced neurotoxicity in a Parkinson's disease (PD) rat model. Parkinson's disease, characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN), is exacerbated by oxidative stress and neuroinflammation. The study involved fifty Wistar rats divided into five groups: control, dimethyl sulfoxide (DMSO) control, Paracentrotus lividus gonadal extract-treated, rotenone-treated, and combined rotenone with Paracentrotus lividus gonadal extract-treated. Behavioral assessments included the rotarod and open field tests, while biochemical analyses measured oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH)), antioxidants (superoxide dismutase (SOD), catalase (CAT)), pro-inflammatory cytokines (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), and neurotransmitters (dopamine (DA), levodopa (L-Dopa)). Histological and immunohistochemical analyses evaluated the neuronal integrity and tyrosine hydroxylase (TH) and alpha-synuclein expression. The results showed that Paracentrotus lividus gonadal extract significantly mitigated rotenone-induced motor deficits and improved locomotor activity. Biochemically, the extract reduced oxidative stress and inflammation markers while enhancing antioxidant levels. Histologically, it restored neuronal integrity and reduced alpha-synuclein accumulation. Molecularly, it increased tyrosine hydroxylase and dopa decarboxylase gene expression, essential for dopamine synthesis. These findings suggest that Paracentrotus lividus gonadal extract exerts neuroprotective effects by modulating oxidative stress, neuroinflammation, and dopaminergic neuron integrity, highlighting its potential as a therapeutic agent for Parkinson's disease.

Investigation of the Effects of Lycopene Against Cisplatin-Induced Renal Damage in Rats: A Histopathological Study

Aim: This study aimed to investigate the protective effect of lycopene (LP) on kidney damage induced by cisplatin (CPT), which is used as a potent agent in chemotherapy, in rats. Material and Method: A total of 35 female Wistar albino rats between 220-250 grams which were 2-4 months old were included in the study. The rats were divided into 5 equal groups as control (Cont) group, CPT group, CPT+LP group, LP group and Dimethyl sulfoxide (DMSO) (solvent) group. Cont group did not receive any treatment during the 7-day long experiment. Rats in the CPT group were administered a single dose of 7 mg/kg CPT intraperitoneally on the first day of the experiment. CPT+LP group was administered 5 mg/kg of LP dissolved in DMSO intraperitoneally every day for 7 days after CPT was administered at the mentioned dose and duration. LP and DMSO groups were intraperitoneally administered 5 mg/kg of LP dissolved in DMSO and 1 ml/kg 0.1% DMSO, respectively during the experiment. At the end of the experiment, kidney tissues taken from the rats were evaluated histopathologically. Results: When the histopathological analyses were evaluated, it was found that glomerular shrinkage, tubular vacuolisation, desquamous epithelium and interstitial hemorrhage were statistically more intense in the CPT group when compared with the Cont, DMSO and LP groups. In the CPT+LP group, cellular organization in the renal tissue was found to be close to normal when compared with the CPT group and it was found that apart from other parameters, especially glomerular atrophy was minimised by LP (p

Characterization of a novel subfamily 1.4 lipase from Bacillus licheniformis IBRL-CHS2: Cloning and expression optimization.

This study focuses on a novel lipase from Bacillus licheniformis IBRL-CHS2. The lipase gene was cloned into the pGEM-T Easy vector, and its sequences were registered in GenBank (KU984433 and AOT80658). It was identified as a member of the bacterial lipase subfamily 1.4. The pCold I vector and E. coli BL21 (DE3) host were utilized for expression, with the best results obtained by removing the enzyme's signal peptide. Optimal conditions were found to be 15°C for 24 h, using 0.2 mM Isopropyl β-D-1-thiogalactopyranoside (IPTG). The His-tagged lipase was purified 13-fold with a 68% recovery and a specific activity of 331.3 U/mg using affinity purification. The lipase demonstrated optimal activity at 35°C and pH 7. It remained stable after 24 h in 25% (v/v) organic solvents such as isooctane, n-hexane, dimethyl sulfoxide (DMSO), and methanol, which enhanced its activity. Chloroform and diethyl ether inhibited the lipase. The enzyme exhibited the highest affinity for p-nitrophenol laurate (C12:0) with a Km of 0.36 mM and a Vmax of 357 μmol min-1 mg-1. Among natural oils, it performed best with coconut oil and worst with olive oil. The lipase was stable in the presence of 1 mM and 5 mM Ca2⁺, K⁺, Na⁺, Mg2⁺, and Ba2⁺, but its activity decreased with Zn2⁺ and Al3⁺. Non-ionic surfactants like Triton X-100, Nonidet P40, Tween 20, and Tween 40 boosted activity, while Sodium Dodecyl Sulfate (SDS) inhibited it. This lipase's unique properties, particularly its stability in organic solvents, make it suitable for applications in organic synthesis and various industries.