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Molecules (Basel, Switzerland) Jun 2024The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] ()....
The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] (). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex () as a promising candidate for further therapeutic exploration.
Topics: Humans; Nickel; Molecular Docking Simulation; Antineoplastic Agents; Ligands; Coordination Complexes; Cell Line, Tumor; Crystallography, X-Ray; MCF-7 Cells; Molecular Structure; Cell Proliferation; Drug Design
PubMed: 38930825
DOI: 10.3390/molecules29122759 -
Molecules (Basel, Switzerland) Jun 20242,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of...
2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal-organic framework with the formula of {[Zn(NDA)(DPBT)] 2HO·3DMF} (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the 2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.
Topics: Metal-Organic Frameworks; Zinc; Thiadiazoles; Biomarkers; Anthrax; Picolinic Acids; Bacillus anthracis; Models, Molecular
PubMed: 38930821
DOI: 10.3390/molecules29122755 -
Medicina (Kaunas, Lithuania) Jun 2024Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be... (Review)
Review
Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Transplantation; Sorafenib; Chemoembolization, Therapeutic; Combined Modality Therapy; Antineoplastic Agents; Bridge Therapy
PubMed: 38929627
DOI: 10.3390/medicina60061010 -
International Journal of Environmental... Jun 2024The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk...
The emerging concern about chemicals in electronic cigarettes, even those without nicotine, demands the development of advanced criteria for their exposure and risk assessment. This study aims to highlight the sensitivity of lung nuclear receptors (NRs) to electronic cigarette e-liquids, independent of nicotine presence, and the influence of the sex variable on these effects. Adult male and female C57BL/6J mice were exposed to electronic cigarettes with 0%, 3%, and 6% nicotine daily (70 mL, 3.3 s, 1 puff per min/30 min) for 14 days, using the inExpose full body chamber (SCIREQ). Following exposure, lung tissues were harvested, and RNA extracted. The expression of 84 NRs was determined using the RT profiler mRNA array (Qiagen). Results exhibit a high sensitivity to e-liquid exposure irrespective of the presence of nicotine, with differential expression of NRs, including one (females) and twenty-four (males) in 0% nicotine groups compared to non-exposed control mice. However, nicotine-dependent results were also significant with seven NRs (females), fifty-three NRs (males) in 3% and twenty-three NRs (female) twenty-nine NRs (male) in 6% nicotine groups, compared to 0% nicotine mice. Sex-specific changes were significant, but sex-related differences were not observed. The study provides a strong rationale for further investigation.
Topics: Animals; Female; Male; Electronic Nicotine Delivery Systems; Mice, Inbred C57BL; Pilot Projects; Mice; Lung; Aerosols; Nicotine; Receptors, Cytoplasmic and Nuclear; Sex Factors
PubMed: 38929056
DOI: 10.3390/ijerph21060810 -
International Journal of Molecular... Jun 2024Hexaazamacrocyclic Schiff bases have been extensively combined with lanthanoid (Ln) ions to obtain complexes with a highly axial geometry. However, the use of flexible...
Hexaazamacrocyclic Schiff bases have been extensively combined with lanthanoid (Ln) ions to obtain complexes with a highly axial geometry. However, the use of flexible hexaazatetraamine macrocycles containing two pyridines and acyclic spacers is rather uncommon. Accordingly, we obtained [DyL(OAc)]OAc·7HO·EtOH and [DyL(Cl)]Cl·2HO, where L and L are the 18-membered macrocycles 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane and 3,10-dimethyl-3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane, respectively, which contain ethylene and methylethylene spacers between their moieties. [DyL(OAc)]OAc·7HO·EtOH represents the first crystallographically characterized lanthanoid complex of L, while [DyL(Cl)]Cl·2HO contributes to increasing the scarce number of Ln compounds containing L. Furthermore, the crystal structure of L·12HO was solved, and it was compared with those of other related macrocycles previously published. Likewise, the crystal structures of the Dy complexes were compared with those of the lanthanoid and -metal complexes of other 18-membered donor macrocycles. This comparison showed some effect of the spacers employed, as well as the influence of the size of the ancillary ligands and the metal ion. Additionally, the distinct folding behaviors of these macrocycles influenced their coordination geometries. Moreover, the luminescent properties of [DyL(OAc)]OAc·7HO·EtOH and [DyL(Cl)]Cl·2HO were also investigated, showing that both complexes are fluorescent, with the emission being sensitized by the ligands.
Topics: Macrocyclic Compounds; Ligands; Coordination Complexes; Lanthanoid Series Elements; Crystallography, X-Ray; Models, Molecular; Molecular Structure
PubMed: 38928512
DOI: 10.3390/ijms25126802 -
International Journal of Molecular... Jun 2024Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic...
Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)-ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN-ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN-ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN-ALK), particularly in those with STRN-ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN-ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients.
Topics: Humans; Crizotinib; Thyroid Carcinoma, Anaplastic; Anaplastic Lymphoma Kinase; Cell Proliferation; Protein Kinase Inhibitors; Apoptosis; Thyroid Neoplasms; Male; Female; Antineoplastic Agents; Middle Aged; Cell Movement; Aged; Oncogene Proteins, Fusion; Tumor Cells, Cultured; Cell Line, Tumor; Calmodulin-Binding Proteins; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38928438
DOI: 10.3390/ijms25126734 -
International Journal of Molecular... Jun 2024The levels of the MMPs in the biological samples of confirmed patients with gastric cancer are significantly elevated compared to those found in healthy people....
Determination of Matrix Metalloproteinase 2 in Biological Samples Using a 3D Stochastic Microsensor Based on Graphene Oxide/AuNanoparticles/(Z)-N-(pyridin-4-yl-methyl) Octadec-9-enamide.
The levels of the MMPs in the biological samples of confirmed patients with gastric cancer are significantly elevated compared to those found in healthy people. Therefore, a novel 3D stochastic microsensor based on graphene oxide, modified with gold nanoparticles and (Z)-N-(pyridin-4-yl-methyl) octadec-9-enamide (namely N2-AuNP/GO), was designed for the determination of MMP-2 in biological samples, and validated for the screening tests of biological samples in order to be used for the early diagnosis of gastric cancer. The proposed sensor presents a low limit of quantification (1.00 × 10 g mL), high sensitivity (1.84 × 10 s g mL), and a wide working concentration range (1.00 × 10-1.00 × 10 g mL). Recovery values higher than 99.15% were recorded for the assay of MMP-2 in whole blood, gastric tissue tumors, saliva, and urine samples.
Topics: Graphite; Humans; Matrix Metalloproteinase 2; Metal Nanoparticles; Gold; Stomach Neoplasms; Biosensing Techniques
PubMed: 38928425
DOI: 10.3390/ijms25126720 -
International Journal of Molecular... Jun 2024The lumen of the endoplasmic reticulum (ER) is usually considered an oxidative environment; however, oxidized thiol-disulfides and reduced pyridine nucleotides occur...
The lumen of the endoplasmic reticulum (ER) is usually considered an oxidative environment; however, oxidized thiol-disulfides and reduced pyridine nucleotides occur there parallelly, indicating that the ER lumen lacks components which connect the two systems. Here, we investigated the luminal presence of the thioredoxin (Trx)/thioredoxin reductase (TrxR) proteins, capable of linking the protein thiol and pyridine nucleotide pools in different compartments. It was shown that specific activity of TrxR in the ER is undetectable, whereas higher activities were measured in the cytoplasm and mitochondria. None of the Trx/TrxR isoforms were expressed in the ER by Western blot analysis. Co-localization studies of various isoforms of Trx and TrxR with ER marker Grp94 by immunofluorescent analysis further confirmed their absence from the lumen. The probability of luminal localization of each isoform was also predicted to be very low by several in silico analysis tools. ER-targeted transient transfection of HeLa cells with Trx1 and TrxR1 significantly decreased cell viability and induced apoptotic cell death. In conclusion, the absence of this electron transfer chain may explain the uncoupling of the redox systems in the ER lumen, allowing parallel presence of a reduced pyridine nucleotide and a probably oxidized protein pool necessary for cellular viability.
Topics: Humans; Thioredoxins; Endoplasmic Reticulum; Oxidation-Reduction; HeLa Cells; Thioredoxin-Disulfide Reductase; Mitochondria; Apoptosis; Cell Survival
PubMed: 38928353
DOI: 10.3390/ijms25126647 -
International Journal of Molecular... Jun 2024Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor...
Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor helix distortions effectively inhibits DNA transcription. In our study, we synthesized and characterized three monofunctional Pt(II) complexes with the general formula [Pt(en)(L)Cl]NO, where en = ethylenediamine, and L = pyridine (py), 2-methylpyridine (2-mepy), and 2-phenylpyridine (2-phpy). The hydrolysis rates of [Pt(en)(py)Cl]NO () and [Pt(en)(2-mepy)Cl]NO () decrease with the bulkiness of the auxiliary ligand with k() = 2.28 ± 0.15 × 10 s and k() = 8.69 ± 0.98 × 10 s at 298 K. The complex [Pt(en)(2-phpy)Cl]Cl () demonstrated distinct behavior. Upon hydrolysis, an equilibrium (K = 0.385 mM) between the complexes [Pt(en)(2-phpy)Cl] and [Pt(en)(2-phpy-H)] was observed with no evidence (NMR or HR-ESI-MS) for the presence of the aquated complex [Pt(en)(2-phpy)(HO)]. Despite the kinetic similarities between phenanthriplatin and (), complexes () and () exhibit minimal activity against A549 lung cancer cell line (IC > 100 μΜ), whereas complex () exhibits notable cytotoxicity (IC = 41.11 ± 2.1 μΜ). In examining the DNA binding of () and () to the DNA model guanosine (guo), we validated their binding through guoN7, which led to an increased population of the C3'- sugar conformation, as expected. However, we observed that the rapid transition E (C2') ↔ E (C3'), in the case of [Pt(en)(py)(guo)](NO) ([-guo]), slows down in the case of [Pt(en)(2-mepy)(guo)](NO) ([-guo]), resulting in separate signals for the two conformers in the H NMR spectra. This phenomenon arises from the steric hindrance between the methyl group of pyridine and the sugar moiety of guanosine. Notably, this hindrance is absent in [-(9-MeG)] (9-MeG = 9-methylguanine), probably due to the absence of a bulky sugar unit in 9-MeG. In the case of (), where the bulkiness of the substitution on the pyridine is further increased by a phenyl group, we observed a notable proximity between 9-MeGH8 and the phenyl ring of 2-phpy. Considering that only () exhibited good cytotoxicity against the A549 cancer cell line, it is suggested that auxiliary ligands, L, with an extended aromatic system and proper orientation in complexes of the type cis-[Pt(en)(L)Cl]NO, may enhance the cytotoxic activity of such complexes.
Topics: Antineoplastic Agents; DNA; Humans; Ligands; Organoplatinum Compounds; Cell Line, Tumor; Hydrolysis; Platinum; A549 Cells
PubMed: 38928230
DOI: 10.3390/ijms25126526 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To explore the effect of UV radiation resistance-associated gene (UVRAG) on ferroptosis induced by sorafenib in leukemia K562 cells.
OBJECTIVE
To explore the effect of UV radiation resistance-associated gene (UVRAG) on ferroptosis induced by sorafenib in leukemia K562 cells.
METHODS
K562 cells were treated with 0, 0.625, 1.25, 2.5, 5, 10, and 20 μmol/L sorafenib for 24 or 48 hours, and the cell viability was detected by CCK-8 assay. Flow cytometry technology was used to detect the changes of reactive oxygen species (ROS) in K562 cells treated with 0, 5, and 10 μmol/L sorafenib for 24 hours. Western blot was used to detect the protein expression of GPX4 in K562 cells treated with 0, 5, and 10 μmol/L sorafenib and pretreatment with ferroptosis inhibitor. A recombinant lentiviral vector was used to construct overexpression cell line in K562 cells. qPCR and Western blot were used to verify gene overexpression, and Western blot detected the effect of on the protein expression of GPX4 and HMGB1 after treatment with sorafenib.
RESULTS
Different concentrations of sorafenib could significantly inhibit the proliferation of K562 cells, and the cell viability gradually decreased with the increase of concentration ( =-0.9841, =-0.9970). The level of ROS was increased (When the concentration was 10 μmol/L, <0.001), while the expression of GPX4 protein was decreased in the process of 0, 5, 10 μmol/L sorafenib-induced K562 cell death ( <0.05), and the decrease in GPX4 protein could be partially reversed by pretreatment with ferroptosis inhibitor ( <0.05). Compared with NC group and NC-Sorafenib group, the expression of GPX4 protein was significantly decreased (both <0.05), while HMGB1 protein was significantly increased (both <0.05).
CONCLUSION
Sorafenib can induce ferroptosis in K562 cells, and this process can be promoted by .
Topics: Sorafenib; Humans; Ferroptosis; K562 Cells; Reactive Oxygen Species; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Cell Survival; HMGB1 Protein
PubMed: 38926949
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.001