Acta biochimica Polonica最新文献

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.

Vitamin D deficiency (VDD) causes a wide range of health problems, including anemia in infants. If not treated promptly, it may create serious issues for infants with long-term impacts. Therefore, a satisfactory solution to this problem is required. This investigation was to explore the correlation between the blood 25-hydroxyvitamin D (25(OH)D) levels and childhood anemia. In this investigation, a cross-sectional examination was performed on 2,942 babies ranging in age from 2 to 36 months and classified into three cohorts: VDD (Vitamin D deficiency), VDI (Vitamin D insufficiency), and VDS (Vitamin D sufficiency). Multiple-variables and multinomially-related logistic regressions for examining the anemia status-vitamin D (Vit-D) relationship of the baseline as the interpretable visual quality models were examined. The median serum 25(OH)D level in 2,942 infants was 24.72±4.26 ng/l, with 661 cases (22.5%) of VDD and 1710 cases of deficiency (58.1%), and a noticeable seasonal variation (p<0.05). Anemia was present in 28.5% of the VDD group compared with 3.3% in vit-D sufficient infants (p<0.0001). Lower levels of 25(OH)D were found to be associated with an increased risk of anemia in a multiple-variable regression analysis. In healthy children, low 25(OH)D levels were associated with increased risk of anemia. Biologically inspired, primary care physicians should assess Vit-D levels and place a greater emphasis on adequate supplementation for deficiency prevention.

This study aimed to investigate the effects of formononetin on triple negative breast cancer (TNBC). Clinical samples were collected from patients with TNBC. Overall survival rates were evaluated using the Kaplan-Meier method. Gene expression was determined using immunohistochemistry, immunofluorescence and western blot. Cellular functions were determined using CCK-8, colony formation and propidium iodide (PI) staining. Xenograft assay was performed to further verify the effects of formononetin (FM) on TNBC. We found that FM combined therapy suppressed the metastasis of TNBC and increased the overall survival rates of TNBC patients. Moreover, FM suppressed the proliferation and induced mitochondrial damage and apoptosis of TNBC cells. FM increased the expression of the BTB domain and CNC homolog 1 (BACH1) in TNBC tissues as well as cells. However, BACH1 knockdown antagonized the effects of FM and promoted the survival of TNBC cells. FM suppressed the tumor growth of TNBC. Taken together, FM suppressed the aggressiveness of TNBC via BACH1/p53 signaling. Therefore, FM may be an alternative strategy for TNBC.

In the development of NAFLD plays an important role the intestinal microflora. Our aim was to characterize role microbiota in children. Distinctive gut microbiota composition was observed in children, characterized and short-chain fatty acid producing bacteria. For the treatment of NAFLD it is possible by therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain the integrity of the intestinal barrier are potential agents.