Acta biochimica Polonica最新文献

Introduction: Acute myeloid leukemia (AML) is a clinically defined heterogeneous disease whose pathophysiology is currently unknown. The association of NAT2 acetylation profiles with human cancer risks, particularly with AML, was investigated in molecular epidemiological studies. Additionally, the NAT2 gene was carried out with acute lymphoid leukemia and other cancers.

Aim: In this case-control study, C481T (rs1799929) and G857A (rs1799931) polymorphism studies were investigated in diagnosed AML patients in the Saudi population.

Methods: This case-control study included 100 AML patients and 100 control subjects recruited in Saudi Arabia. The C481T and G857A polymorphisms were genotyped using specific primers and restriction enzymes. Statistical analysis was performed on the AML patients and controls using chi-square tests, genotyping, and allele frequencies (odds ratios, 95% of confidence intervals, and P-values).

Results: Hardy Weinberg Equilibrium was determined to be both within and outside of the G857A and C481T polymorphisms. The allele and genotyping frequencies in AML and control subjects were analyzed, and the results corroborated the unfavorable connection with C481T (CC vs CT+TT; OR-1.12; (95% CIs: 0.64-1.96); P=0.67 and T vs C; OR-0.89; (95% CIs: 0.59-1.35) and P=0.60) and G857A polymorphisms (GG vs GA+AA; OR-1.50; (95% CIs: 0.83-2.71); P=0.17 and A vs G; OR-0.71; (95%CIs: 0.43-1.19) and P=0.19) in the NAT2 gene.

Conclusion: The study results revealed a negative correlation as well as a protective factor for AML with the C481T and G857A polymorphisms in the NAT2 gene.

Brain metastases (BM) are associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Considering that, LGAS8-AS1-mediated progression of BM was probed in NSCLC. The clinical characteristics of 60 NSCLC patients (30 without BM and 30 with BM) were analyzed. NSCLC patients with BM had higher levels of LGALS8-AS1 than NSCLC patients without BM. Depleting LGALS8-AS1 prevented NSCLC cell proliferation, migration, invasion, and angiogenesis in vitro, and NSCLC tumorigenesis and BM in vivo. LGALS8-AS1 targeted miR-885-3p to mediate Fascin actin-bundling protein 1 (FSCN1) expression. Restoring miR-885-3p inhibited NSCLC growth, angiogenesis, and BM, and FSCN1 induction rescued the performance of LGALS8-AS1 depletion on NSCLC cells. Our results provide new insights into LGALS8-AS1-mediated NSCLC metastasis and suggest that LGALS8-AS1 may be a useful biomarker for identifying NSCLC with metastatic potential.

This study aimed to investigate the efficacy and safety of vitamin D supplementation in the treatment of allergic rhinitis (AR) using mometasone. A total of 140 patients with moderate and severe AR treated at our hospital between January 2017 and August 2020 were recruited as subjects for this study. The patients were randomly divided into control and experimental groups, with 70 patients in each group. Mometasone nasal spray was used in both groups, and vitamin D was administered to the experimental group for four weeks. The total nasal symptom scores (TNSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to assess the efficacy of treatment. T lymphocyte subsets (CD3+, CD4+ and CD8+) and serum anti-inflammatory and proinflammatory cytokines such as interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were analyzed. The incidence of adverse reactions was recorded. Serum vitamin D levels were lower in patients with AR. After 4 weeks of treatment, total TNSS scores, T lymphocyte subsets (CD3+, CD4+), CD4+/CD8+ ratio, TNF-α, and total RQLQ scores were significantly reduced compared to the initial testing (P<0.05) in the two groups; CD8+, IFN-γ, and IL-10 levels as well as serum vitamin D were significantly increased compared to the initial test (P<0.05). The improvement in these parameters in the experimental group was significantly greater than that in the control group (P<0.05), except for sneezing and eye symptoms in the TNSS and RQLQ scores. It was concluded that vitamin D supplementation improves the therapeutic effect of mometasone nasal spray on AR and is thus recommended as an adjuvant therapy for moderate and severe AR.

This study investigated the biological role and mechanism of circMETTL15 in colorectal cancer (CRC). Cancer tissues and matched adjacent normal tissues were collected. CircMETTL15, miR-374a-5p, and ESCO2 levels were detected by RT-qPCR and Western Blot. LoVo cells were selected for loss- and gain-of-function assays and rescue assays. Cell proliferation was detected by CCK-8 and colony formation tests, cell apoptosis and cell cycle were detected by flow cytometry, cell migration and invasion were detected by Transwell assay, and protein expression of ki-67, E-cadherin, N-cadherin, and cleaved caspase-3 was detected by Western blot. Through bioinformatics analysis and verification assays, the targeting relationship between circMETTL15, miR-374a-5p, and ESCO2 was studied. The results suggest that circMETTL15 was a stable circRNA that was highly expressed in CRC tissues and cells and was associated with tumor size, higher TNM staging, and lymph node metastasis in CRC patients. Functionally, knocking down circMETTL15 inhibited the proliferation, migration, invasion, and EMT of LoVo cells, and induced apoptosis. Overexpression of circMETTL15 showed the opposite effect. The effects of knockdown or overexpression of circMETTL15 on the biological behavior of LoVo cells were reversed by knockdown of miR-374a-5p or knockdown of ESCO2, respectively. Mechanistically, circMETTL15 acts as a ceRNA for miR-374a-5p to regulate ESCO2 expression, thereby promoting the biological behavior of LoVo cells. In conclusion, the results of this study reveal the role of circMETTL15 in CRC and the underlying molecular mechanism, which provides potential data support for the development of future CRC drugs.

Effective therapeutic strategies are urgently required to enhance the prognosis of patients suffering from KRAS mutations. Owing to the undruggable nature of KRAS, targeting downstream signaling pathways, namely PI3K/AKT/mTOR, shows antiproliferative and apoptotic effects. Unfortunately, targeting this pathway upregulates autophagy, contributing to reduced drug efficacy. Therefore, it was reasonable to use a combination of kinase inhibitors and autophagy inhibitors to achieve a higher therapeutic benefit. The impact of Dactolisib, a dual PI3K/mTOR inhibitor, and Lys05, a dimeric chloroquine, was tested on the survival of breast cancer MCF-7 and lung cancer A549 cells. The dose selection for the optimal effect of the Dactolisib/Lys05 combination was determined using CompuSyn software. This combinatorial effect was evaluated using various methodologies, such as expression profile analysis for autophagic, proliferative, and apoptotic markers. These effects were corroborated by ELISA, Western blot, and flow cytometry using the Annexin V-FITC apoptosis detection kit. A549 cells treated in a 2:1 ratio of Lys05 and Dactolisib demonstrated a synergistic effect on cell death, proliferation, and apoptotic gene markers, in addition to its effect on autophagic gene and protein markers, showing an enhanced effect compared to monotherapy. Therefore, the PI3K/AKT kinase inhibitor/autophagy inhibitor combination establishes higher therapeutic benefits on A549 cells compared to kinase inhibitor monotherapy.

The chemiluminescence (CL) methods unlike the other methods of determining free radicals (FR) allow investigating the kinetics of the derivation and recombination of radicals/antioxidants, and thus the development and attenuation of the process/processes after excitation in time. However, these methods are of limited application because the knowledge of the explored parameters is insufficient (maximum intensity and integrated area under the kinetics plot). The kinetics is studied by the CL methods and a new parameter (IR-criterion) of analysis of damping of the initiated CL dynamics has been introduced. The IR-criterion parameter: identifies the relationship between the rates of initiation and recombination of peroxide radicals in blood-serum samples; allows the full straightening of the CL curves; provides new information in the considered pathological processes; can serve as an additional universal characteristic of FR activity of blood serum in pathological processes.

The homochirality of biological molecules is one of the basic mysteries of biogenesis. The predominance of l-amino acids and d-hydrocarbons in living matter stands in contrast to the chemical principle of symmetry between enantiomers. An answer to the puzzle needs to include a plausible explanation of how the natural racemic balance was initially tipped in favor of one enantiomer and how the initial tiny excess was amplified to significant levels. It is also necessary to consider how the imbalance was sustained from returning to a thermodynamic equilibrium. This is a review of the main concepts and observations, followed by a brief discussion.

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anti-cancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The "Lipinski five rules," on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or non-aquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.

Mercury is a major pollutant in the environment due to its high concentration in the soil. In this study, a mercuric reductase was extracted from Pseudomonas aeruginosa. The sequence of the enzyme was retrieved from the literature and structural homologs were identified. The protein bonded with Mercuric compounds and their interaction was briefly studied. Autodock Vina was used to perform a molecular docking with the target protein. Results showed that the sequence consists of most of the random coil 44.74% followed by α-helix and B-turns. Moreover, the protein was predicted to have a FAD/NAD(P)-binding domain. The virulence factor prediction using different approaches of Virulentpred and VICMpred suggested that P00392 is non-toxic. Next, the mutational analyses were performed to predict the active site residues in the resulting models and to determine mutants. The results show that the enzyme is involved in the bioremediation of mercury by using in-silico techniques. Finally, molecular docking studies were conducted on the best-selected model to find the active site residues and to generate a pattern of interaction to understand the mode of action of the substrate and its catalytic activity which refers to the binding with mercury.

MicroRNA-22 (miR-22) has been reported to exert a neuroprotective effect. However, the specific role and mechanism of miR-22 in ischemia/reperfusion (I/R)-induced brain injury are still not known well. In this study, we evaluated whether miR-22 participates in I/R-induced neuronal injury and the potential mechanism by using an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. Our results showed that miR-22 was significantly down-regulated in SH-SY5Y cells suffering from OGD/R. Up-regulation of miR-22 by its specific mimic could protect SH-SY5Y cells against OGD/R-induced injury. The luciferase reporter assay demonstrated that T-cell lymphoma invasion and metastasis 1 (Tiam1) was a direct target of miR-22. MiR-22 mimic obviously inhibited Tiam1 expression in OGD/R-exposed SH-SY5Y cells. Tiam1 siRNA could attenuate OGD/R-induced SH-SY5Y cell injury. In addition, Tiam1 siRNA reduced the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) in OGD/R-exposed SH-SY5Y cells, and up-regulation of Rac1 activity could attenuate the neuroprotective effect of miR-22 up-regulation. Furthermore, OGD/R exposure led to increased methylation of miR-22, and the demethylating agent 5-Aza-dC significantly up-regulated miR-22 expression and inhibited Tiam1 expression and Rac1 activation. Taken together, our results demonstrated that DNA methylation-mediated miR-22 down-regulation aggravated I/R-induced neuron injury by promoting the activation of Tiam1/Rac1 signals. Our findings provide a deeper understanding of I/R-induced brain injury and suggest that miR-22 may be a promising therapeutic target for this disease.