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Toxins Jun 2024The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not...
The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.
Topics: Cyanobacteria Toxins; Humans; Microcystins; Marine Toxins; Water Purification; Adsorption; Bacterial Toxins; Alkaloids; Magnetite Nanoparticles; Tropanes; Nanostructures; Uracil; Cyanobacteria; Cell Survival; Water Pollutants, Chemical
PubMed: 38922163
DOI: 10.3390/toxins16060269 -
Toxics May 2024The need to develop advanced wastewater treatment techniques and their use has become a priority, the main goal being the efficient removal of pollutants, especially...
The need to develop advanced wastewater treatment techniques and their use has become a priority, the main goal being the efficient removal of pollutants, especially those of organic origin. This study presents the photo-degradation of a pharmaceutical wastewater containing Kabi cytarabine, using ultraviolet (UV) radiation, and a synthesized catalyst, a composite based on bismuth and iron oxides (BFO). The size of the bandgap was determined by UV spectroscopy, having a value of 2.27 eV. The specific surface was determined using the BET method, having a value of 0.7 m g. The material studied for the photo-degradation of cytarabine presents a remarkable photo-degradation efficiency of 97.9% for an initial concentration 0f 10 mg/L cytarabine Kabi when 0.15 g of material was used, during 120 min of interaction with UV radiation at 3 cm from the irradiation source. The material withstands five photo-degradation cycles with good results. At the same time, through this study, it was possible to establish that pyrimidine derivatives could be able to combat infections caused by and .
PubMed: 38922085
DOI: 10.3390/toxics12060405 -
Dentistry Journal May 2024Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing...
BACKGROUND
Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and .
METHODS
We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking.
RESULTS
Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in .
CONCLUSIONS
Curcumin affects both host carious processes and .
PubMed: 38920854
DOI: 10.3390/dj12060153 -
Biosensors May 2024In this study, we report a multiplexed platform for the simultaneous determination of five marine toxins. The proposed biosensor is based on a disposable electrical...
In this study, we report a multiplexed platform for the simultaneous determination of five marine toxins. The proposed biosensor is based on a disposable electrical printed (DEP) microarray composed of eight individually addressable carbon electrodes. The electrodeposition of gold nanoparticles on the carbon surface offers high conductivity and enlarges the electroactive area. The immobilization of thiolated aptamers on the AuNP-decorated carbon electrodes provides a stable, well-orientated and organized binary self-assembled monolayer for sensitive and accurate detection. A simple electrochemical multiplexed aptasensor based on AuNPs was designed to synchronously detect multiple cyanotoxins, namely, microcystin-LR (MC-LR), Cylindrospermopsin (CYL), anatoxin-α, saxitoxin and okadaic acid (OA). The choice of the five toxins was based on their widespread presence and toxicity to aquatic ecosystems and humans. Taking advantage of the conformational change of the aptamers upon target binding, cyanotoxin detection was achieved by monitoring the resulting electron transfer increase by square-wave voltammetry. Under the optimal conditions, the linear range of the proposed aptasensor was estimated to be from 0.018 nM to 200 nM for all the toxins, except for MC-LR where detection was possible within the range of 0.073 to 150 nM. Excellent sensitivity was achieved with the limits of detection of 0.0033, 0.0045, 0.0034, 0.0053 and 0.0048 nM for MC-LR, CYL, anatoxin-α, saxitoxin and OA, respectively. Selectivity studies were performed to show the absence of cross-reactivity between the five analytes. Finally, the application of the multiplexed aptasensor to tap water samples revealed very good agreement with the calibration curves obtained in buffer. This simple and accurate multiplexed platform could open the window for the simultaneous detection of multiple pollutants in different matrices.
Topics: Marine Toxins; Biosensing Techniques; Microcystins; Gold; Aptamers, Nucleotide; Electrochemical Techniques; Saxitoxin; Metal Nanoparticles; Cyanobacteria Toxins; Bacterial Toxins; Uracil; Tropanes; Alkaloids; Okadaic Acid; Electrodes; Limit of Detection
PubMed: 38920572
DOI: 10.3390/bios14060268 -
Journal of Cardiothoracic Surgery Jun 2024We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses....
Graft protective effects and donor-specific antibody suppression by CD4CD25Foxp3 regulatory T cell induced by HMG-CoA reductase inhibitor rosuvastatin in a murine heart transplant model.
BACKGROUND
We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation.
METHODS
CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 μg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed.
RESULTS
CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time [MST], 7 days). CBA mice treated with 500 μg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4Foxp3 cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4CD25Foxp3 T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4CD25Foxp3 Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients.
CONCLUSION
Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4CD25Foxp3 Tregs.
Topics: Animals; Rosuvastatin Calcium; Heart Transplantation; T-Lymphocytes, Regulatory; Mice; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice, Inbred C57BL; Mice, Inbred CBA; Graft Rejection; Graft Survival; Interleukin-2 Receptor alpha Subunit; Male; Forkhead Transcription Factors; Disease Models, Animal; Flow Cytometry
PubMed: 38918849
DOI: 10.1186/s13019-024-02888-4 -
BMC Cancer Jun 2024High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual...
High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.
Topics: Humans; Animals; Proto-Oncogene Proteins c-bcl-2; Dihydroorotate Dehydrogenase; Mice; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic; Proto-Oncogene Proteins c-myc; Xenograft Model Antitumor Assays; Drug Synergism; Cell Line, Tumor; Oxidoreductases Acting on CH-CH Group Donors; Apoptosis; Lymphoma, B-Cell; Gene Rearrangement; Cell Proliferation; Biphenyl Compounds; Quinaldines
PubMed: 38918775
DOI: 10.1186/s12885-024-12534-w -
BMC Public Health Jun 2024Pre-exposure prophylaxis (PrEP) with oral emtricitabine/tenofovir disoproxil (FTC/TDF) proved highly efficient in preventing HIV. Since 09/2019, FTC/TDF-PrEP is covered...
BACKGROUND
Pre-exposure prophylaxis (PrEP) with oral emtricitabine/tenofovir disoproxil (FTC/TDF) proved highly efficient in preventing HIV. Since 09/2019, FTC/TDF-PrEP is covered by health insurances in Germany, if prescribed by licensed specialists. However, methods to longitudinally monitor progress in PrEP implementation in Germany are lacking.
METHODS
Utilizing anonymous FTC/TDF prescription data from 2017-2021, we developed a mathematical model to disentangle HIV-treatment from PrEP prescriptions, as well as to translate PrEP prescriptions into number of PrEP users. We used the model to estimate past- and future PrEP uptake dynamics, to predict coverage of PrEP needs and to quantify the impact of COVID-19 on PrEP uptake on a national and regional level.
RESULTS
We identified significant (p<0.01) decelerating effects of the first- and second COVID-19-lockdown on PrEP uptake in 04/2020 and 12/2020. We estimated 26,159 (CI: 25,751-26,571) PrEP users by 12/2021, corresponding to 33% PrEP coverage of people in need. We projected 64,794 (CI: 62,956-66,557) PrEP users by 12/2030, corresponding to 81% PrEP coverage. We identified profound regional differences, with high PrEP coverage and uptake in metropoles and low coverage in more rural regions.
CONCLUSIONS
Our approach presents a comprehensive solution to monitor and forecast PrEP implementation from anonymous data and highlighted that the COVID-19 pandemic significantly decelerated PrEP uptake in Germany. Moreover, slow PrEP uptake in rural areas indicate that structural barriers in PrEP care, education or information exist that may hamper the goal of ending the AIDS epidemic by 2030.
Topics: Humans; Pre-Exposure Prophylaxis; Germany; HIV Infections; COVID-19; Anti-HIV Agents; Male; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Female; Models, Theoretical; Adult
PubMed: 38918748
DOI: 10.1186/s12889-024-19198-y -
BMC Microbiology Jun 20245-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and...
Prebiotic fibre mixtures counteract the manifestation of gut microbial dysbiosis induced by the chemotherapeutic 5-Fluorouracil (5-FU) in a validated in vitro model of the colon.
BACKGROUND
5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient's prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts.
METHODS
A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin.
RESULTS
We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control.
CONCLUSIONS
These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies.
Topics: Fluorouracil; Prebiotics; Dysbiosis; Gastrointestinal Microbiome; Humans; Dietary Fiber; Colon; Bacteria; Male; Fatty Acids, Volatile; Female; Adult; Pectins
PubMed: 38918717
DOI: 10.1186/s12866-024-03384-4 -
Asian Pacific Journal of Cancer... Jun 2024Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A Randomized Single-Blinded Phase II Trial Comparing Efficacy and Quality of Life of Topical Aloe Vera Gel Plus Urea Cream Versus Urea Cream Alone for Prevention of Hand Foot Syndrome in Cancer Patients Receiving Capecitabine.
INTRODUCTION
Capecitabine has been widely prescribed to treat various cancers. The hand foot syndrome (HFS) is the most troublesome adverse effect. Urea cream has been pre-emptively co-prescribed, even though its efficacy is doubtful. Aloe vera gel with urea cream might potentiate each other. This trial was intended to prove the efficacy of this combination.
MATERIALS AND METHODS
The investigators conducted a randomized single-blinded phase II study. The participants were randomized 1:1 to receive the combination of aloe vera gel and 10% urea cream (n = 30), the experimental A+U arm and 10% urea cream alone (n = 31), the U arm. The sample size was calculated to have 90% power to show the significant 20% reduction in the incidence of HFS grade 2-3 of the combination therapy with alpha level = 0.05. Both the CTCAE criteria version 5 and the dermatology life quality index (DLQI) were assessed to determine the severity of HFS and quality of life, respectively.
RESULTS
Most of the participants had rectal cancer (A+U: 43.3%; U: 41.9%). In the A+U group, 86.7% had grade 0-1 HFS and 13.3% had grade 2-3 HFS. In the U group, 64.5% had grade 0-1 HFS and 35.5% had grade 2-3 HFS (Mann-Whitney U test, p = 0.045). Grade 2-3 HFS was significantly lower in the combination group.
CONCLUSION
Combination of aloe vera gel and 10% urea cream ameliorated the severity of HFS in participants taking capecitabine; however, no significant difference in DLQI between the groups was demonstrated.
Topics: Humans; Capecitabine; Female; Male; Middle Aged; Quality of Life; Hand-Foot Syndrome; Urea; Antimetabolites, Antineoplastic; Single-Blind Method; Plant Preparations; Prognosis; Follow-Up Studies; Adult; Administration, Topical; Aged; Neoplasms; Skin Cream; Aloe
PubMed: 38918684
DOI: 10.31557/APJCP.2024.25.6.2203 -
Asian Pacific Journal of Cancer... Jun 2024Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone...
BACKGROUND
Tongue cancer is the most prevalent type of oral cancer. Recently, natural compounds have been considered important resources for several anticancer drugs. Thymoquinone (TQ) exhibits a potent anti-cancer effect. 5-Fluorouracil (5-FU) is a chemotherapeutic drug that has been utilized in the treatment of cancer. Recently, combination therapy has gained popularity as a treatment option for patients with cancer.
OBJECTIVES
The present study was carried out to assess the cytotoxic effect of 5-Fluorouracil (5-FU), Thymoquinone (TQ), and their combination on tongue squamous cell carcinoma cell line (HNO-97).
METHODS
Tongue carcinoma cell line (HNO-97) was maintained in cultured flasks and the cells were divided into four groups; group Ι: control untreated group, group ΙΙ: HNO-97-treated cells with different concentrations of 5-FU from 0.5 µM/ml to 3µM/ml, group ΙIΙ: HNO-97-treated cells with different concentrations of TQ from 7.25µM/ml to 23.05µM/ml, and group ΙV: HNO-97-treated cells with both 5-FU and TQ in serial concentrations till (IC50) in a dose of 27.44 µM/ml. Determination of the cytotoxic effect of the tested agents on the HNO-97 cell line was done using methyl thiazole tetrazolium assay, nuclear morphometric analysis, microscopic examination, and annexin-v/ propidium iodide staining assay.
RESULT
The findings revealed that the cytotoxic effect of 5-FU, TQ, and their combination on tongue squamous cell carcinoma cell line (HNO-97) was dose-dependent. The microscopic examination revealed that 5-FU, TQ alone, or their combination induced apoptotic cell death. P-value < 0.05 was statistically significant.
CONCLUSION
The combination of 5-FU and TQ produced a marked cytotoxic effect on HNO-97 cells.
Topics: Humans; Fluorouracil; Benzoquinones; Tongue Neoplasms; Carcinoma, Squamous Cell; Apoptosis; Cell Proliferation; Tumor Cells, Cultured; Antineoplastic Combined Chemotherapy Protocols; In Vitro Techniques; Cell Line, Tumor; Drug Synergism
PubMed: 38918680
DOI: 10.31557/APJCP.2024.25.6.2169