Search Results (13)

Background: This study systematically investigates the therapeutic effects of naringenin (NAR) and oleuropein (OLE) on prostate cancer through miR-155-5p regulation. Methods: Experimental studies conducted on MAT-LyLu prostate cancer cell lines revealed that the application of NAR (50 μM) and OLE (75 μM) significantly increased miR-155-5p expression by 2.89-fold and 1.74-fold, respectively (p < 0.05). Bioinformatics analyses have indicated that miR-155-5p interacts with critical oncogenic pathways such as KRAS, CDK2, NF-κB, and TGF-β/Smad2. Computational analyses have revealed that miR-155-5p interacts with 16 critical oncogenic targets, including KRAS and CDK2. Molecular docking studies showed that NAR binds to the Switch I/II region of KRAS with a binding energy of −8.2 kcal/mol, while OLE binds to the ATP-binding pocket of CDK2 with an affinity of −9.1 kcal/mol. Pharmacokinetic evaluations revealed that NAR indicated high oral bioavailability (93.763% HIA) and full compliance with Lipinski’s rules, while OLE required advanced formulation strategies due to its high polarity. Network pharmacology analyses have shown that NAR affects lysosomal functions and enzyme regulation, while OLE affects G protein-coupled receptors and oxidoreductase activity. Results: Results indicate that NAR and OLE exhibit antitumor effects through multiple mechanisms by increasing miR-155-5p expression and inhibiting critical oncogenic targets in prostate cancer. Conclusions: Findings suggest that the dietary intake of these natural compounds (citrus and olive products) should be considered in prostate cancer prevention strategies, shedding light on the epigenetic mechanisms of polyphenols in cancer treatment and contributing to the development of new therapeutic strategies. Full article

Uniparental disomies (UPDs) are among the causes of imprinting disorders. Specific phenotypes of most causative UPDs have been described. Here, we describe the case of a 2-year-old female patient who presented a syndromic phenotype. Chromosomal microarray analysis revealed UPD of the whole chromosome 16. Microsatellite analysis demonstrated paternal origin of the UPD and its isodisomic pattern (UPiD (16) pat). Mosaic trisomy 16 was not detected using the FISH method. Whole-exome sequencing revealed no pathogenetic genetic variants sufficient to explain the syndromic phenotype nor unmasked pathogenic recessive genetic variants on chromosome 16. Whole-genome trio DNA sequencing revealed no additional candidate pathogenic genetic variants to those detected by whole-exome sequencing, including miRNAs and lncRNAs. Imprinting disorders at 6q24.2, 7p12.2, 7q32.2, 11p15.5, 14q32.2, 15q11.2, and 20q13.32, as well as multilocus imprinting disturbances (MLIDs), were excluded by Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA). At the same time, we detected abnormal hypermethylation of the ZNF597 transcription start site differentially methylated region (ZNF597:TSS-DMR), accompanied by hypomethylation of the neighbouring ZNF597:3′ DMR. Both DMRs were normally imprinted, and the DNA alterations in our patient with UPD (16) pat are opposite to those previously described for maternal uniparental disomy (UPD (16) mat). To date, several cases of UPD (16) pat have been reported. Our case report describes the syndromic phenotype of a patient with paternal uniparental disomy of chromosome 16 in contrast to the previously described patients with a normal phenotype or with abnormal phenotypes caused by acquired homozygosity of pathogenic variants at autosomal recessive genes located on this chromosome. Reporting such observations will help systematize data on the phenotypes of imprinting disorders on chromosome 16. Full article

Leptospirosis is a globally significant zoonosis affecting animal health, productivity, and the environment. While typically associated with tropical climates, its persistence in semi-arid regions such as La Laguna, Mexico—characterized by low humidity, high temperatures, and limited water sources—remains poorly understood. Although these adverse environmental conditions theoretically limit the survival of Leptospira, high livestock density and synanthropic reservoirs (e.g., rodents) may compensate, facilitating transmission. In this cross-sectional study, blood sera from 445 dairy cows (28 herds: 12 intensive [MI], 16 semi-intensive [MSI] systems) were analyzed via microscopic agglutination testing (MAT) against 10 pathogenic serovars. Urine samples were cultured for active Leptospira detection. Risk factors were assessed through epidemiological surveys and multivariable analysis. This study revealed an overall apparent seroprevalence of 27.0% (95% CI: 22.8–31.1), with significantly higher rates in MSI (54.1%) versus MI (12.2%) herds (p < 0.001) and an estimated true seroprevalence of 56.3% (95% CI: 50.2–62.1) in MSI and 13.1% (95% CI: 8.5–18.7) in MI herds (p < 0.001). The Sejroe serogroup was isolated from urine in both systems, confirming active circulation. In MI herds, rodent presence (OR: 3.6; 95% CI: 1.6–7.9) was identified as a risk factor for Leptospira seropositivity, while first-trimester abortions (OR:10.1; 95% CI: 4.2–24.2) were significantly associated with infection. In MSI herds, risk factors associated with Leptospira seropositivity included co-occurrence with hens (OR: 2.8; 95% CI: 1.5–5.3) and natural breeding (OR: 2.0; 95% CI: 1.1–3.9), whereas mastitis/agalactiae (OR: 2.8; 95% CI: 1.5–5.2) represented a clinical outcome associated with seropositivity. Despite semi-arid conditions, Leptospira maintains transmission in La Laguna, particularly in semi-intensive systems. The coexistence of adapted (Sejroe) and incidental serogroups underscores the need for targeted interventions, such as rodent control in MI systems and poultry management in MSI systems, to mitigate both zoonotic and economic impacts. Full article

Alzheimer’s disease (AD) is the most common form of dementia, characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles, leading to neuronal loss and cognitive impairments. Recent studies have reported the dysregulation of RNA splicing in AD pathogenesis. Our previous transcriptomic study demonstrated the neuroprotective effect of the phytocannabinoid cannabinerol (CBNR) against the cell viability loss induced by Aβ in differentiated SH-SY5Y cells. This study also highlighted the deregulation of genes involved in mRNA splicing after Aβ exposure or CBNR pre-treatment. Here, we investigated whether CBNR could restore the splicing defects induced by Aβ in an AD in vitro model. Using the rMATS computational tool for detecting differential alternative splicing events (DASEs) from RNA-Seq data, we obtained 96 DASEs regulated in both conditions and, remarkably, they were all restored by CBNR pre-treatment. The pathway analysis indicated an over-representation of the “Alzheimer’s disease–amyloid secretase pathway”. Additionally, we observed that Aβ exposure increased the frequency of retained introns (RIs) among the shared DASEs, and that this frequency returned to normality by CBNR pre-treatment. Interestingly, most of these RIs contain a premature in-frame stop codon within the RNA sequence. Finally, analyzing the DASE regions for miRNA hybridization, we found 33 potential DASE/miRNA interactions that were relevant in AD pathogenesis. These findings revealed a novel trans-gene regulation by CBNR, potentially explaining part of its neuroprotective role. This is the first study demonstrating the involvement of a cannabinoid in the regulation of mRNA splicing in an AD model. Full article

This review examines the use of magneto-acoustic methods to measure electrical conductivity. It focuses on two techniques developed in the last two decades: Magneto-Acoustic Tomography with Magnetic Induction (MAT-MI) and Magneto-Acousto-Electrical Tomography (MAET). These developments have the potential to change the way medical doctors image biological tissue. Full article

Wheat (Triticum aestivum L.) is a key food crop, accounting for approximately 765 million tons produced worldwide. The present study evaluated 16 wheat genotypes using 19 morphological and phenological traits, 16 molecular markers (Inter Simple Sequence Repeats and Start Codon Targeted; ISSR and SCoT) and rbcL and matK plastid gene barcoding. The 16 wheat genotypes showed significant genetic variation using the markers assayed. Cell plot of phenological parameters revealed significant differences among the 16-day-old seedlings of wheat genotypes at Z1.1 growth stage. Collectively, W2 genotype had the lowest shoot length (SL), length of first internodes (LFI) and leaf area (LA) values, while W8 genotype had the highest diameter of first internode (DFI) and LA values. Furthermore, W7 genotype had the maximum plant biomass (PB) and leaf width (LW) values. Geometric models grouped wheat kernels into “rounded” and “nearly elongated”. Estimates of heritability (H²) for these morphological characters ranged from 4.93 to 100%. The highest H² values were recorded for root number (RN) (100%) followed by SL (88.72%), LFI (88.30%), LA (87.76%) and Feret diameter (86.68%), while the lowest H² value was recorded for DFI (4.93%). Furthermore, highly significant genotypic and phenotypic correlations were also observed among those traits. Reproducible fingerprinting profiles and high levels of polymorphism (PPB%) of SCoT (95.46%) and ISSR (82.41%) were recorded, indicating that they are effective tools for detecting genetic variation levels among wheat genotypes. The informativeness of markers were measured through estimation of polymorphic information content (PIC), resolving power (RP) and marker index (MI). The RP and PPB% of SCoT were significantly higher compared to those of ISSR. Comparatively, the two molecular markers were effective for studying genetic diversity among wheat genotypes, but SCoT markers were more informative. Moreover, based on the two chloroplast DNA regions (rbcL and matK), MatK was found to be more reliable for differentiating among T. aestivum genotypes. Taken together, using all the studied attributes, a clear taxonomic relationship can be used to identify T. aestivum species and improve their pragmatic production and development. Full article

The circadian rhythm of melatonin secretion in the pineal gland is highly conserved in vertebrates. Melatonin levels are always elevated at night. Acetylserotonin O-methyltransferase (ASMT) is the last enzyme in the regulation of melatonin biosynthesis (N-acetyl-5-hydroxytryptamine-melatonin). S-adenosylmethionine (SAM) is an important methyl donor in mammals and can be used as a substrate for the synthesis of melatonin. Methionine adenosyltransferase (MAT) catalyzes the synthesis of SAM from methionine and ATP and has a circadian rhythm. CircRNA is an emerging type of endogenous noncoding RNA with a closed loop. Whether circRNAs in the pineal gland can participate in the regulation of melatonin synthesis by binding miRNAs to target mat2a as part of the circadian rhythm is still unclear. In this study, we predicted the targeting relationship of differentially expressed circRNAs, miRNAs and mRNAs based on the results of rat pineal RNA sequencing. Mat2a siRNA transfection confirmed that mat2a is involved in the synthesis of melatonin. Circ-ERC2 and miR-125a-5p were screened out by software prediction, dual-luciferase reporter experiments, cell transfection, etc. Finally, we constructed a rat superior cervical ganglionectomy model (SCGx), and the results showed that circ-ERC2 could participate in the synthesis of melatonin through the miR-125a-5p/MAT2A axis. The results of the study revealed that circ-ERC2 can act as a molecular sponge of miR-125a-5p to regulate the synthesis of melatonin in the pineal gland by targeting mat2a. This experiment provides a basis for research on the circadian rhythm of noncoding RNA on pineal melatonin secretion. Full article

Rice (Oryza sativa L.) is cultivated in a wide range of climatic conditions, thereby inducing great variations in the rice growth, yield and quality. However, the comprehensive effects of temperature and solar radiation under different ecological regions on the rice growth, yield and quality are not well understood, especially in a middle rice cropping system. The rice growth, yield- and quality-related traits were investigated under different ecological regions. Among different areas, the days before the heading stage and after the heading stage of six cultivars ranged from 80 to 120 and from 30 to 50. The gaps of the grain yield, head rice rate, chalky grain rate and chalkiness level were about 1.2–52.4%, 1.0–3.0%, 2.7–12.7% and 0.3–4.5%, respectively. This study demonstrated that in these regions, temperature is a limiting factor compared with radiation. Moreover, the rice growth, yield and quality were closely associated with daily air (DT), maximum (MaT), minimum (MiT) and effective accumulated temperatures (EAT). An excellent rice growth, a high grain yield and an excellent quality could be achieved if the EAT was higher than 1592 °C·d and the MiT was lower than 23.1 °C before the heading stage, and if the DT, MiT and MaT were lower than 25.7 °C, 22.0 °C and 30 °C after the heading stage, respectively. These findings served as an important reference for optimizing cultivar selection for a specific area and determining suitable areas for a certain variety. Full article

Background and Objectives: The excessive use of smartphones for various tasks led to a new adverse postural phenomenon called text neck. The aim of this study was to investigate the effect of the text neck posture (TNP) on static occlusion by using the T-Scan III occlusal diagnostic system. Materials and Methods: Nineteen subjects (aged 20 to 24 years) were considered for this research. They had normal values for anterior overbite and overjet, Angle Class I occlusion, no posterior crossbite, and no signs or symptoms of cervical or temporo-mandibular disorders. Occlusal registrations were performed with the T-Scan III system in a normal, neutral head posture (NHP), as well as in the TNP. The investigated parameters were: occlusion time (OT), asymmetry index of the occlusal force (AOF), percent of the maximum movie force (%MMF), and the time elapsed from the last occlusal contact until the maximum intercuspation (MAT-OTB). The last three parameters were analyzed in the maximum area frame (MA) of the registrations. For the statistical analysis of the recorded data, the Wilcoxon Signed Ranks test and the Spearman’s correlation coefficient were used. Results: The following values were obtained in NHP and in TNP: for AOF, 14.88 ± 10.39% and 18.04 ± 12.83%, respectively; for OT, 1.34 ± 1.84 s and 1.32 ± 1.8 s, respectively; for the %MMF, 97.5 ± 2.83% and 96.31 ± 3.17%, respectively; for MAT-OTB, 2.08 ± 1.82 s and 1.45 ± 2.3 s, respectively. There were no statistically significant differences between the static occlusal parameters measured in NHP and those in TNP. However, the high values of the AOF and OT in NHP revealed an imbalance of the occlusal force distribution between the right and left side in maximum intercuspation (MI), as well as a lack of simultaneity of static occlusal contacts. Furthermore, there was a significant, direct, and strong correlation between OT and AOF in NHP. Conclusions: The NHP should not be used as the starting position in TNP simulations in T-Scan studies, so as to avoid statistically insignificant differences between static occlusion in NHP and TNP. The healthy standing subjects, with normal occlusal relationships from the clinical point of view, revealed an occlusal instability in NHP when examined with the T-Scan. Full article

Hybrid composites composed of bio-based thin-ply carbon fibre prepreg and flame-retardant mats (E20MI) have been produced to investigate the effects of laminate design on their fire protection performance and mechanical properties. These flame-retardant mats rely primarily on expandable graphite, mineral wool and glass fibre to generate a thermal barrier that releases incombustible gasses and protects the underlying material. A flame retardant (FR) mat is incorporated into the carbon fibre bio-based polymeric laminate and the relationship between the fire protection properties and mechanical properties is investigated. Hybrid composite laminates containing FR mats either at the exterior surfaces or embedded 2-plies deep have been tested by the limited oxygen index (LOI), vertical burning test and cone calorimetry. The addition of the surface or embedded E20MI flame retardant mats resulted in an improvement from a base line of 33.1% to 47.5% and 45.8%, respectively. All laminates passed the vertical burning test standard of FAR 25.853. Cone calorimeter data revealed an increase in the time to ignition (TTI) for the hybrid composites containing the FR mat, while the peak of heat release rate (PHRR) and total heat release (TTR) were greatly reduced. Furthermore, the maximum average rate of heat emission (MARHE) values indicated that both composites with flame retardant mats had achieved the requirements of EN 45545-2. However, the tensile strengths of laminates with surface or embedded flame-retardant mats were reduced from 1215.94 MPa to 885.92 MPa and 975.48 MPa, respectively. Similarly, the bending strength was reduced from 836.41 MPa to 767.03 MPa and 811.36 MPa, respectively. Full article

Elucidating the neural correlates of mobility is critical given the increasing population of older adults and age-associated mobility disability. In the current study, we applied graph theory to cross-sectional data to characterize functional brain networks generated from functional magnetic resonance imaging data both at rest and during a motor imagery (MI) task. Our MI task is derived from the Mobility Assessment Tool–short form (MAT-sf), which predicts performance on a 400 m walk, and the Short Physical Performance Battery (SPPB). Participants (n = 157) were from the Brain Networks and Mobility (B-NET) Study (mean age = 76.1 ± 4.3; % female = 55.4; % African American = 8.3; mean years of education = 15.7 ± 2.5). We used community structure analyses to partition functional brain networks into communities, or subnetworks, of highly interconnected regions. Global brain network community structure decreased during the MI task when compared to the resting state. We also examined the community structure of the default mode network (DMN), sensorimotor network (SMN), and the dorsal attention network (DAN) across the study population. The DMN and SMN exhibited a task-driven decline in consistency across the group when comparing the MI task to the resting state. The DAN, however, displayed an increase in consistency during the MI task. To our knowledge, this is the first study to use graph theory and network community structure to characterize the effects of a MI task, such as the MAT-sf, on overall brain network organization in older adults. Full article

This paper is devoted to an analytical approach to the magnetoacoustic tomography with magnetic induction (MAT-MI) problem for three-layer low-conductivity objects. For each layer, we determined closed-form analytical expressions for the eddy current density and Lorentz force vectors based on the separation of variables method. Next, the analytical formulas were validated with numerical solutions obtained with the help of the finite element method (FEM). Based on the acoustic dipole radiation theory, the influence of the transducer reception pattern on MAT-MI was investigated. To obtain acoustic wave patterns, as a system transfer function we proposed the Morlet wavelet. Finally, image reconstruction examples for objects of more complex shapes are presented, and the influence of the MAT-MI scanning resolution and the presence of the noise on the image reconstruction quality was studied in detail. Full article

Several researchers have analyzed the alterations of the methionine cycle associated with liver disease to clarify the pathogenesis of human hepatocellular carcinoma (HCC) and improve the preventive and the therapeutic approaches to this tumor. Different alterations of the methionine cycle leading to a decrease of S-adenosylmethionine (SAM) occur in hepatitis, liver steatosis, liver cirrhosis, and HCC. The reproduction of these changes in MAT1A-KO mice, prone to develop hepatitis and HCC, demonstrates the pathogenetic role of MAT1A gene under-regulation associated with up-regulation of the MAT2A gene (MAT1A:MAT2A switch), encoding the SAM synthesizing enzymes, methyladenosyltransferase I/III (MATI/III) and methyladenosyltransferase II (MATII), respectively. This leads to a rise of MATII, inhibited by the reaction product, with a consequent decrease of SAM synthesis. Attempts to increase the SAM pool by injecting exogenous SAM have beneficial effects in experimental alcoholic and non-alcoholic steatohepatitis and hepatocarcinogenesis. Mechanisms involved in hepatocarcinogenesis inhibition by SAM include: (1) antioxidative effects due to inhibition of nitric oxide (NO•) production, a rise in reduced glutathione (GSH) synthesis, stabilization of the DNA repair protein Apurinic/Apyrimidinic Endonuclease 1 (APEX1); (2) inhibition of c-myc, H-ras, and K-ras expression, prevention of NF-kB activation, and induction of overexpression of the oncosuppressor PP2A gene; (3) an increase in expression of the ERK inhibitor DUSP1; (4) inhibition of PI3K/AKT expression and down-regulation of C/EBPα and UCA1 gene transcripts; (5) blocking LKB1/AMPK activation; (6) DNA and protein methylation. Different clinical trials have documented curative effects of SAM in alcoholic liver disease. Furthermore, SAM enhances the IFN-α antiviral activity and protects against hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic hepatitis B virus (HBV) infection. However, although SAM prevents experimental tumors, it is not curative against already established experimental and human HCCs. The recent observation that the inhibition of MAT2A and MAT2B expression by miRNAs leads to a rise of endogenous SAM and strong inhibition of cancer cell growth could open new perspectives to the treatment of HCC. Full article