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Dental Materials : Official Publication... Jun 2024The commonly used base monomer utilized in resinous commercial dental restorative products is bis-GMA which is derived from bisphenol-A (BPA) - a well-known compound...
OBJECTIVE
The commonly used base monomer utilized in resinous commercial dental restorative products is bis-GMA which is derived from bisphenol-A (BPA) - a well-known compound which may disrupt endocrine functions. To address concerns about its leaching into the oral environment and to optimize the quality of dental composites, a BPA-free alternative base monomer, fluorinated urethane dimethacrylate (FUDMA), was designed by modifying a UDMA monomer system.
METHODS
Nine groups of composites were prepared by mixing the base monomers and TEGDMA in a ratio of 70/30 wt% to which were added silanized glass particles (mean diameter: 0.7 µm) in 3 different volume fractions (40, 45, and 50 vol%). Bis-GMA and UDMA base monomers were used as control groups in the same ratios. Various properties including degree of conversion (DC), flexural strength (FS) and flexural modulus (FM), water sorption (WS), solubility (SL), surface hardness and roughness, and initial adhesion property against S.mutans were investigated. One-way analysis of variance followed by Bonferroni test at α = 0.05 was used to analyze the results.
RESULTS
A significant difference in FS between FUDMA-based composite with 40 vol% filler (120.3 ± 10.4 MPa) and Bis-GMA-based composite with the same filler fraction (105.8 ± 10.0 MPa) was observed but there was no significant difference among other groups. The UDMA based group exhibited the highest WS (1.3 ± 0.3 %). Bis-GMA showed greater initial bacterial adhesion but was not statistically different from the other groups (p = 0.082).
SIGNIFICANCE
FUDMA-based resin composites exhibit comparable mechanical and bacterial adhesion properties compared with Bis-GMA and UDMA-based composites. The FUDMA composites show positive outcomes indicating they could be used as substitute composites to Bis-GMA-based composites.
PubMed: 38926013
DOI: 10.1016/j.dental.2024.06.024 -
Anticancer Research Jul 2024Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of...
BACKGROUND/AIM
Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of cancer, including breast cancer. However, the effect of PEMF stimulation on the efficacy of doxorubicin and the underlying mechanisms remain unclear. Thus, this study aimed to investigate the effect of PEMF stimulation on the anticancer activity of doxorubicin in MDA-MB-231 human breast cancer cells.
MATERIALS AND METHODS
MDA-MB-231 cells were seeded and allowed to incubate for 48 h. The cells were treated with doxorubicin, cisplatin, 5-fluorouracil, or paclitaxel for 48 h. Subsequently, the cells were stimulated with a 60-min PEMF session thrice a day (with an interval of 4 h between each session) for 24 or 48 h. Cell viability was assessed by trypan blue dye exclusion assay and cell-cycle analysis was analyzed by flow cytometry. Molecular mechanisms involved in late G arrest were confirmed by a western blot assay and confocal microscopy.
RESULTS
MDA-MB-231 cells treated with a combination of doxorubicin and PEMF had remarkably lower viability than those treated with doxorubicin alone. PEMF stimulation increased doxorubicin-induced cell-cycle arrest in the late G phase by suppressing cyclin-dependent kinase 1 (CDK1) activity through the enhancement of myelin transcription factor 1 (MYT1) expression, cell division cycle 25C (CDC25C) phosphorylation, and stratifin (14-3-3σ) expression. PEMF also increased doxorubicin-induced DNA damage by inhibiting DNA topoisomerase II alpha (TOP2A).
CONCLUSION
These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
Topics: Humans; Doxorubicin; Breast Neoplasms; Female; Cell Line, Tumor; Cell Survival; G2 Phase Cell Cycle Checkpoints; Electromagnetic Fields; DNA Topoisomerases, Type II; Cell Proliferation; Paclitaxel; Fluorouracil; Poly-ADP-Ribose Binding Proteins; cdc25 Phosphatases; Cyclin-Dependent Kinase 2
PubMed: 38925852
DOI: 10.21873/anticanres.17096 -
Phytochemical Analysis : PCA Jun 20242,6-Disubstituted piperidin-3-ols are an important group of piperidine alkaloids found in species such as Senna spectabilis, whose main constituents include cassine and...
INTRODUCTION
2,6-Disubstituted piperidin-3-ols are an important group of piperidine alkaloids found in species such as Senna spectabilis, whose main constituents include cassine and spectaline, compounds with relevant pharmacological activity. The analysis of these compounds is challenging due to the complexity of plant extracts and the absence of chromophores capable of absorbing ultraviolet (UV) radiation.
OBJECTIVE
This paper presents a new analytical method to separate and quantify the non-UV-absorbing alkaloids present in ethanol extracts from S. spectabilis flowers using capillary zone electrophoresis (CZE) with indirect UV detection.
METHODOLOGY
The optimized CZE method employs a background electrolyte containing 60 mM histidine (His), 15 mM α-cyclodextrin, 20% acetonitrile (ACN), and pH-adjusted to 4.7 with acetic acid (AcOH).
RESULTS
The limit of detection (LOD) values was 10.2 and 13.9 mg L for cassine and spectaline, respectively. For both analytes, the precision data were better than 2% of relative standard deviation (RSD) for migration times and peak areas. To evaluate the applicability of the developed method, ethanolic extracts from S. spectabilis flowers were prepared and analyzed.
CONCLUSIONS
Thereby, the method proved to be efficient and complementary to conventional techniques, offering a cost-effective alternative in the quantification of the non-UV-absorbing piperidine alkaloids present in plant extracts.
PubMed: 38925584
DOI: 10.1002/pca.3411 -
International Journal of Pharmaceutics Jun 2024Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a...
Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose. Subsequently, nanogels were formed by subjecting α-cyclodextrin and the hydrophobically modified mannose to magnetic stirring in water. By adjusting the mole ratio between the hydrophobically modified mannose and α-cyclodextrin, nanogels with an average 100-150 nm diameter were obtained. Physicochemical and structural analyses by H NMR and X-ray diffraction unveiled a supramolecular and hierarchical mechanism underlying the creation of these nanogels. The proposed mechanism of nanogel formation involves two distinct steps: initial interaction of hydrophobically modified mannose with α-cyclodextrin resulting in the formation of inclusion complexes, followed by supramolecular interactions among these complexes, ultimately leading to nanogel formation after 72 h of stirring. We demonstrated the nanogels' ability to encapsulate a short peptide ([p-BuF, R]SHf) as a water-soluble drug model. This discovery holds promise for potentially utilizing these nanogels in drug delivery applications.
PubMed: 38925235
DOI: 10.1016/j.ijpharm.2024.124379 -
Forensic Science International Jun 2024Determining the biological source of a stain can be important information for both investigators and the judiciary in criminal cases. Immunochromatographic assays are...
Determining the biological source of a stain can be important information for both investigators and the judiciary in criminal cases. Immunochromatographic assays are commonly used in forensic science for the identification of human biological material. It has previously been demonstrated that various environmental, thermal and chemical insults can affect the efficacy of ABAcard® HemaTrace® in the detection of human blood. In this study, the efficacy of three tests - ABAcard® HemaTrace®, ABAcard® p30, and RSID™-Saliva - was determined for the detection of blood, semen, and saliva respectively, after the fluids had been exposed to adverse environmental conditions. Each biological fluid was deposited on cotton swatches and exposed to infrared (IR) light using a 100 W heat lamp emitting IR light between 620 and 750 nm and heat of 32° for 24, 36 and 48 h. Cotton swatches bearing biological fluids were also buried in outdoor soil for 3, 4 and 5 weeks. To test common forensic scenarios where biological material may be exposed to solar light, samples were placed on a car bonnet and left for 24, 36 and 48 h. ABAcard® HemaTrace® was able to detect haemoglobin in blood that had been exposed to IR and solar light up to 48 h. False negative ABAcard® HemaTrace® results were obtained from 60 % of blood samples buried for 3 and 4 weeks, and 80 % of blood samples buried for 5 weeks. ABAcard® p30 was able to detect p30 in semen that had been exposed to IR and solar light up to 48 h, except for one false negative after 48 h of IR exposure. False negative ABAcard® p30 results were obtained from all semen samples buried for 3, 4 and 5 weeks. RSID™-Saliva was able to detect α-amylase in saliva in all instances, with no false negative results observed. The findings from this study highlight the need to consider the context in which human blood, semen and saliva are found when reporting on negative immunoassay results.
PubMed: 38924941
DOI: 10.1016/j.forsciint.2024.112106 -
Journal of the National Cancer Institute Jun 2024The microbiome has been associated with chemotherapy and immune checkpoint inhibitor (ICI) efficacy. How this pertains to resectable esophageal carcinoma (EC) is...
BACKGROUND
The microbiome has been associated with chemotherapy and immune checkpoint inhibitor (ICI) efficacy. How this pertains to resectable esophageal carcinoma (EC) is unknown. Our aim was to identify microbial signatures in resectable EC associated with response to neoadjuvant chemoradiotherapy (nCRT) with or without ICI.
METHODS
From two prospectively collected EC cohorts (n = 172 in total) treated with nCRT alone (n = 132) or a combination of nCRT and ICI (n = 40), fecal samples were available at baseline, during treatment, and pre-surgery. Additionally, in the ICI treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor and duodenal DNA were extracted for 16S rRNA sequencing. Associations were investigated between microbiome composition pathological complete response (pCR) and progression-free survival (PFS).
RESULTS
There was a significant shift in the microbiota profile of the fecal, tumor and duodenal microbiota over time. In the total cohort, patients with a pCR had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment, p = 0.036. Pre-surgery, lower alpha diversity (<4.12) was related to worse PFS, log-rank p = 0.025. Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS, log-rank p = 0.012.
CONCLUSIONS
Lower intestinal alpha diversity was associated with worse response and survival of EC patients. In tumor biopsies Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for EC patients.
PubMed: 38924513
DOI: 10.1093/jnci/djae153 -
Cancer Medicine Jun 2024The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with...
BACKGROUND
The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.
METHODS
This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.
RESULTS
We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.
CONCLUSIONS
The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Quinolines; Phenylurea Compounds; Male; Female; Middle Aged; Retrospective Studies; Aged; Prognosis; Antineoplastic Agents; Adult
PubMed: 38923354
DOI: 10.1002/cam4.7410 -
Toxins May 2024α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer...
α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection map. At this resolution, no major conformational changes between the crystalline and solution states of α-LTX tetramers were observed. Electrophysiological studies showed that, under the conditions of crystallization, α-LTX simultaneously formed multiple channels in biological membranes that displayed coordinated gating. Two types of channels with conductance levels of 120 and 208 pS were identified. Furthermore, we observed two distinct tetramer conformations of tetramers both when observed as monodisperse single particles and within the 2D crystals, with pore diameters of 11 and 13.5 Å, suggestive of a flickering pore in the middle of the tetramer, which may correspond to the two states of toxin channels with different conductance levels. We discuss the structural changes that occur in α-LTX tetramers in solution and propose a mechanism of α-LTX insertion into the membrane. The propensity of α-LTX tetramers to form 2D crystals may explain many features of α-LTX toxicology and suggest that other pore-forming toxins may also form arrays of channels to exert maximal toxic effect.
Topics: Cryoelectron Microscopy; Animals; Spider Venoms; Cell Membrane; Protein Multimerization; Crystallization
PubMed: 38922143
DOI: 10.3390/toxins16060248 -
Asian Pacific Journal of Cancer... Jun 2024With earlier prostate cancer (PCa) diagnosis and increased survivorship, post-treatment quality of life (QoL) has become increasingly important. The Expanded Prostate...
BACKGROUND
With earlier prostate cancer (PCa) diagnosis and increased survivorship, post-treatment quality of life (QoL) has become increasingly important. The Expanded Prostate Cancer Index Composite (EPIC) is a widely adopted QoL instrument for PCa. We aimed to create a Punjabi version of EPIC to further research in the Punjabi-speaking population.
METHODS
A prototype of the Punjabi version of EPIC was created by forward-backward translations and revision. After concluding the cultural adaptation phase by interviewing 15 participants, a pilot version was created. Validation of the pilot version was performed by having 72 participants complete the Punjabi EPIC and another commonly used QoL instrument, the EORTC QLQ-c30, twice within a 4-week period. Test retest reliability (Pearson's correlations and difference distribution) and internal consistency (Cronbach's alpha) were measured using SAS version 9.4.
RESULTS
Modifications were needed for the prototype Punjabi version after forward-backward translations. Cultural adaptation has highlighted a few issues including syntax and terminology. Test-retest reliability of the Urinary, Bowel, Sexual and Hormone domains were 0.88, 0.91, 0.91, and 0.95, respectively, and subscale correlations ranged from 0.75 to 0.93. Internal consistency for domains and subscales was good except for Sexual Domain. Performance of EPIC is comparable, and in some cases, slightly better than validated Punjabi version of EORTC QLQ-C30.
CONCLUSIONS
The EPIC questionnaire was successfully translated into Punjabi and was culturally adapted. The resultant Punjabi version has high reliability and validity and will be an important tool for QoL research in the Punjabi population. EPIC was successfully translated, culturally adapted, and validated with high reliability and validity into Punjabi. It will be a valuable QoL tool for physicians in clinical and research settings, and for patients in decision-making.
Topics: Humans; Male; Quality of Life; Surveys and Questionnaires; Prostatic Neoplasms; Reproducibility of Results; Middle Aged; Aged; Psychometrics; Prognosis; Translations; Follow-Up Studies; Pilot Projects; India
PubMed: 38918655
DOI: 10.31557/APJCP.2024.25.6.1945 -
Communications Biology Jun 2024The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub...
The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.
Topics: Cryoelectron Microscopy; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Molecular Dynamics Simulation; Humans; Holoenzymes; Protein Multimerization; Animals
PubMed: 38918547
DOI: 10.1038/s42003-024-06423-y