This study aimed to assess antimicrobial efficacy, cytotoxicity, and cytokine release (IL-1b, IL-6, IL-10, TNF-α) from human dental pulp stem cells (hDPSCs) of chitosan (CH) and hydroxyapatite ...(HAp)-modified glass ionomer cements (GIC).
GICs with varied CH and HAp concentrations (0 %, 0.16 %, 2 %, 5 %, 10 %) were tested against S. mutans for 24 h or 7 days. Antimicrobial activity was measured using an MTT test. Cytotoxicity evaluation followed for optimal concentrations, analyzing mitochondrial activity and apoptosis in hDPSCs. Cytokine release was assessed with MAGPIX. Antimicrobial analysis used Shapiro-Wilk, Kruskal-Wallis, and Dunnett tests. Two-way ANOVA, Tukey, and Dunnett tests were applied for hDP metabolism and cytokine release.
CH 2 % and HAp 5 % significantly enhanced GIC antimicrobial activity, especially after seven days. In immediate analysis, all materials showed reduced mitochondrial activity compared to the control. After 24 h, CH demonstrated mitochondrial metabolism similar to the control. All groups exhibited mild cytotoxicity (∼30 % cell death). Only IL-6 was influenced, with reduced release in experimental groups.
CH 2 % and HAp 5 % were most effective for antibacterial effects. GIC-CH 2 % emerged as the most promising formula, displaying significant antibacterial effects with reduced hDPSC toxicity.
•GICs with 2 % Chitosan and 5 % hydroxyapatite have higher antibacterial properties.•IL-1b, IL-10 and TNF-a released from hDPSCs are not modulated by modified GICs.•GIC containing 2 % Chitosan has low cytotoxicity with higher antibacterial properties.
Current treatment for Glioblastoma Multiforme (GBM) is not efficient due to its aggressive nature, tendency to infiltrate surrounding brain tissue, and chemotherapy resistance. Tetrahydroquinoline ...scaffolds are emerging as a new class of drug for treating many human cancers including GBM. This study investigates the cytotoxicity effect of eight novel derivatives of 2-((3,4-dihydroquinolin-1(2H)-yl)(aryl)methyl)phenol, containing substitute 1 with reduced dihydroquinoline fused with cyclohexene ring and substitute 2 with phenyl and methyl group. The 4-position of the aryl ring was determinant for the desired cytotoxicity, and out of the 8 synthesized compounds, the 4-trifluoromethyl substituted derivative (4ag) exhibited the most anti-GBM potential effect compared to the standard chemotherapeutic agent, temozolomide (TMZ), with IC50 values of 38.3 μM and 40.6 μM in SNB19 and LN229 cell lines, respectively. Our results demonstrated that 4ag triggers apoptosis through the activation of Caspase-3/7. In addition, 4ag induced intracellular reactive oxygen species (iROS) which in turn elevated mitochondrial ROS (mtROS) and causes the disruption of the mitochondrial membrane potential (Δψmt) in both GBM cells. This compound also exhibited anti-migratory properties over the time in both the cell lines. Overall, these findings suggest that tetrahydroquinoline derivative, 4ag could lead to the development of a new drug for treating GBM.
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Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage ...hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1+effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.
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•trans-Differentiation of cytotoxic Th17 to Th1 cells promotes liver pathology•CX3CR1+CD8Teff cells inhibit fibrosis by granzyme-mediated killing of fibroblasts•Defective induction of hepatic B cell tolerance promotes autoimmunity in infants•B-cell-modifying therapies promote immune recovery in infants with biliary atresia
Liver immune profiling in infants with biliary atresia suggests B-cell-modifying therapies may alleviate liver pathology
The highly variable response rates to immunotherapies underscore our limited knowledge about how tumors can manipulate immune cells. Here the membrane topology of natural killer (NK) cells from ...patients with liver cancer showed that intratumoral NK cells have fewer membrane protrusions compared with liver NK cells outside tumors and with peripheral NK cells. Dysregulation of these protrusions prevented intratumoral NK cells from recognizing tumor cells, from forming lytic immunological synapses and from killing tumor cells. The membranes of intratumoral NK cells have altered sphingomyelin (SM) content and dysregulated serine metabolism in tumors contributed to the decrease in SM levels of intratumoral NK cells. Inhibition of SM biosynthesis in peripheral NK cells phenocopied the disrupted membrane topology and cytotoxicity of the intratumoral NK cells. Targeting sphingomyelinase confers powerful antitumor efficacy, both as a monotherapy and as a combination therapy with checkpoint blockade.
Ten pentacyclic triterpenoids including a new multiflorane triterpene acid, 2α,3β,23-trihydroxymultiflor-7-en-28-oic acid (1), and a new lupane triterpene monoglucoside named akebiaoside C (2), were ...obtained from the leaves of
. Their structures were elucidated by extensive spectroscopic analysis, and they were all isolated from the leaves of
for the first time. These compounds, except 4 and 5, showed
α-glucosidase inhibitory activity much stronger than acarbose. Especially, 2, 3, 6, 8 and 10 displayed
α-glucosidase inhibitory activity with IC
values from 0.004 to 0.081 mM, which were close or even more potent than corosolic acid (IC
0.06 mM). Triterpenoids 1, 8 and 10 were further revealed to show moderate
cytotoxic activity against human tumor A549, HeLa and HepG2 cell lines, with IC
values ranging from 26.5 to 51.9 μM. Compound 9 selectively showed
cytotoxicity toward HeLa and HepG2 cell lines, with IC
values of 81.49 and 73.47 μM, respectively. These findings provided new data to support that the leaves of
are a rich source in bioactive triterpenoids highly valuable to be developed for medicinal usage.
Oncolytic viruses for cancer immunotherapy Hemminki, Otto; Dos Santos, João Manuel; Hemminki, Akseli
Journal of hematology and oncology,
06/2020, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to elucidate how versatile ...viruses are, and how they can be used to complement other cancer therapies to gain optimal patient benefits. Historical reports from over a hundred years suggest treatment efficacy and safety with adenovirus and other oncolytic viruses. This is confirmed in more contemporary patient series and multiple clinical trials. Yet, while the first viruses have already been granted approval from several regulatory authorities, room for improvement remains.As good safety and tolerability have been seen, the oncolytic virus field has now moved on to increase efficacy in a wide array of approaches. Adding different immunomodulatory transgenes to the viruses is one strategy gaining momentum. Immunostimulatory molecules can thus be produced at the tumor with reduced systemic side effects. On the other hand, preclinical work suggests additive or synergistic effects with conventional treatments such as radiotherapy and chemotherapy. In addition, the newly introduced checkpoint inhibitors and other immunomodulatory drugs could make perfect companions to oncolytic viruses. Especially tumors that seem not to be recognized by the immune system can be made immunogenic by oncolytic viruses. Logically, the combination with checkpoint inhibitors is being evaluated in ongoing trials. Another promising avenue is modulating the tumor microenvironment with oncolytic viruses to allow T cell therapies to work in solid tumors.Oncolytic viruses could be the next remarkable wave in cancer immunotherapy.
Background and purpose: Cilostazol is a prescription medication for intermittent claudication in patients with peripheral artery disease. Previous research has demonstrated that this 2-oxoquinoline ...derivative possesses antithrombotic, vasodilator, antimitogenic, and antioxidant effects. Cilostazol exerts its products through the inhibition of PDE3 activity and the prevention of cAMP degradation. The present study aimed to examine the protective properties of cilostazol against carboplatin-induced cytotoxicity and genotoxicity in Beas-2B and human blood lymphocyte cells. Materials and methods: cells were pre-treated with different concentrations of cilostazol (5, 25, 50, and 100 μM) with carboplatin at an optimum cytotoxic dosage (9.2 µM). The MTT and micronucleus assays were used to assess cytotoxicity and genotoxicity. Statistical analysis was performed using the one-way ANOVA in Prism Ver. 8 software. Results: The cytotoxic effect of carboplatin was dose-dependent, as evidenced by the 48h culture treatment with concentrations of 0.3, 1, 3, 10, and 30 µM. Pre-treatment of cilostazol at 25, 50, and 100 µM with carboplatin at 9.2 µM enhanced cell viability in Beas-2B cells compared to the carboplatin alone as positive control. Additionally, cilostazol at 50 and 100 µM showed its potent genoprotective effects via micronucleus assay against carboplatin at IC50 at blood lymphocyte cells. Conclusion: Cilostazol provided conceivable protective effects by modulating cytotoxicity and genotoxicity induced by carboplatin in Beas-2B and human blood lymphocyte cells.
Zinc oxide (ZnO) is the most commonly used nanoparticles among different nanoparticles. Its applications ranged from personal care products, sensors, antibacterial creams, and biomedical ...applications. The broad range of applications raises concern in regards to their potential toxicity. Therefore, it is required to understand their toxicity mechanism and pattern on various levels. The primary aim of this review is to summarize the cytotoxicity, genotoxicity, neurotoxicity, and developmental toxicity of ZnO nanoparticles in various kinds of cells in vitro and in vivo. Literatures available on ZnO nanoparticles toxicity suggest that dissolution, organism dependent cellular uptake, generation of reactive oxygen species (ROS), and induced inflammatory responses seem to be common factors which govern the toxicity of ZnO nanoparticles.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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