Search Results (1,287)

Placenta and visceral adipose tissue (VAT) are implicated in the development of gestational diabetes mellitus (GDM). In the present study, we examined the whole-transcriptomic profile of both tissues in GDM women to elucidate the molecular basis of GDM pathogenesis. The whole-transcriptome profile was analyzed in placenta and VAT from at-term patients with GDM and controls using RNA-seq. qPCR was used to validate several differentially expressed genes (DEGs). A total of 179 DEGs were observed in the placenta and 4 in VAT, including both up- and downregulated genes. The expression of the selected mRNAs for validation was consistent with the sequencing results. An analysis of the placental upregulated DEGs in the GDM women showed enrichment in functions including the G-protein-coupled receptor signaling pathway, organophosphate biosynthetic process, and phospholipid metabolic process, while the downregulated DEGs were enriched in cell motility and the cell migration process. The target pathways of DEGs in VAT are related to cancer and to the activation of the complement cascade. Molecular pathways involved in G-protein-coupled receptor signaling, the organophosphate biosynthetic process, the phospholipid metabolic process, and cell motility and cell migration are altered in the placentas of GDM women. Moreover, a disordered complement cascade might take place in the VAT of GDM women. Full article

The development of low-resistance blood flow within the developing placenta in the early weeks of pregnancy requires trophoblast invasion of the uterine spiral arteries. Therefore, understanding the migration and differentiation of trophoblasts is necessary. Recently, researchers have focused increasingly on the regulation of the response of endovascular extravillous trophoblasts (enEVTs) to mechanical stimuli associated with shear stress. The starting point for these studies is that enEVTs, which adopt a pseudoendothelial phenotype, functionally resemble endothelial cells in terms of ability to promote angiogenesis, vascular remodeling and cell–cell communication. The complex process of mechanotransduction requires the coordinated participation of many types of mechanoreceptors, whose activated signaling pathways are translated into whole-cell mechanosensing involving components of the cytoskeleton and extracellular matrix. The aim of this review is to comprehensively present the current knowledge on the importance of mechanical stimuli associated with shear stress in the development of local changes in the vascular system at the site of blastocyst implantation. The characteristics of individual mechanoreceptors are determined, and the most important factors influencing mechanotransduction are discussed. Understanding the importance of mechanosensing disorders in trophoblasts in the pathogenesis of unexplained recurrent abortions or preeclampsia may be helpful in the development of new therapeutic strategies based on the regulation of mechanotransduction in response to shear stress. Full article

Evidence of possible cerebellar involvement in spatial processing, place learning and other types of higher order functions comes mainly from clinical observations, as well as from mutant mice and lesion studies. The latter, in particular, have reported deficits in spatial learning and memory following surgical or neurotoxic cerebellar ablation. However, the low specificity of such manipulations has often made it difficult to precisely dissect the cognitive components of the observed behaviors. Likewise, due to conflicting data coming from lesion studies, it has not been possible so far to conclusively address whether a cerebellar dysfunction is sufficient per se to induce learning deficits, or whether concurrent damage to other regulatory structure(s) is necessary to significantly interfere with cognitive processing. In the present study, the immunotoxin 192 IgG-saporin, selectively targeting cholinergic neurons in the basal forebrain and a subpopulation of cerebellar Purkinje cells, was administered to adult rats bilaterally into the basal forebrain nuclei, the cerebellar cortices or both areas combined. Additional animals underwent injections of the toxin into the lateral ventricles. Starting from two–three weeks post-lesion, the animals were tested on paradigms of motor ability as well as spatial learning and memory and then sacrificed for post-mortem morphological analyses. All lesioned rats showed no signs of ataxia and no motor deficits that could impair their performance in the water maze task. The rats with discrete cerebellar lesions exhibited fairly normal performance and did not differ from controls in any aspect of the task. By contrast, animals with double lesions, as well as those with 192 IgG-saporin given intraventricularly did manifest severe impairments in both reference and working memory. Histo- and immunohistochemical analyses confirmed the effects of the toxin conjugate on target neurons and fairly similar patterns of Purkinje cell loss in the animals with cerebellar lesion only, basal forebrain-cerebellar double lesions and bilateral intraventricular injections of the toxin. No such loss was by contrast seen in the basal forebrain-lesioned animals, whose Purkinje cells were largely spared and exhibited a normal distribution pattern. The results suggest important functional interactions between the ascending regulatory inputs from the cerebellum and those arising in the basal forebrain nuclei that would act together to modulate the complex sensory–motor and cognitive processes required to control whole body movement in space. Full article

Electrochemical impedance spectroscopy (EIS) is widely used at the laboratory level for monitoring/diagnostics of battery cells, but the design and validation of in situ, online measurement systems based on EIS face challenges due to complex hardware–software interactions and non-idealities. This study aims to develop an integrated co-simulation framework to support the design, debugging, and validation of EIS measurement systems devoted to the online monitoring of battery cells, helping to predict experimental results and identify/correct the non-ideality effects and sources of uncertainty. The proposed framework models both the hardware and software components of an EIS-based system to simulate and analyze the impedance measurement process as a whole. It takes into consideration the effects of physical non-idealities on the hardware–software interactions and how those affect the final impedance estimate, offering a tool to refine designs and interpret test results. For validation purposes, the proposed general framework is applied to a specific EIS-based laboratory prototype, previously designed by the research group. The framework is first used to debug the prototype by uncovering hidden non-idealities, thus refining the measurement system, and then employed as a digital model of the latter for fast development of software algorithms. Finally, the results of the co-simulation framework are compared against a theoretical model, the real prototype, and a benchtop instrument to assess the global accuracy of the framework. Full article

Background: Sarcopenia is characterized by a loss of muscle mass and strength, resulting in functional limitations and an increased risk of falls, injuries and fractures. The aim of this study was to obtain detailed information on skeletal muscle changes in patients with multiple myeloma (MM) during treatment. Methods: A total of 51 patients diagnosed with MM who had undergone whole-body low-dose computed tomography acquisition prior to induction therapy (T1) and post autologous stem cell transplantation (T2) were examined retrospectively. Total volume (TV), muscle volume (MV) and intramuscular adipose tissue volume (IMAT) of the autochthonous back muscles, the iliopsoas muscle and the gluteal muscles were evaluated on the basis of the resulting masks of the BOA tool with the fully automated combination of TotalSegmentator and a body composition analysis. An in-house trained artificial intelligence network was used to obtain a fully automated three-dimensional segmentation assessment. Results: Patients’ median age was 58 years (IQR 52–66), 38 were male and follow-up CT-scans were performed after a mean of 11.8 months (SD ± 3). Changes in MV and IMAT correlated significantly with Body-Mass-Index (BMI) (r = 0.7, p < 0.0001). Patients (n = 28) with a decrease in BMI (mean −2.2 kg/m²) during therapy lost MV (T1: 3419 cm³, IQR 3176–4000 cm³ vs. T2: 3226 cm³, IQR 3014–3662 cm³, p < 0.0001) whereas patients (n = 20) with an increased BMI (mean +1.4 kg/m²) showed an increase in IMAT (T1: 122 cm³, IQR 96.8–202.8 cm³ vs. T2: 145.5 cm³, IQR 115–248 cm³, p = 0.0002). Loss of MV varied between different muscle groups and was most prominent in the iliopsoas muscle (−9.8%) > gluteus maximus (−9.1%) > gluteus medius (−5.8%) > autochthonous back muscles (−4.3%) > gluteus minimus (−1.5%). Increase in IMAT in patients who gained weight was similar between muscle groups. Conclusions: The artificial intelligence-based three-dimensional segmentation process is a reliable and time-saving method to acquire in-depth information on sarcopenia in MM patients. Loss of MV and increase in IMAT were reliably detectable and associated with changes in BMI. Loss of MV was highest in muscles with more type 2 muscle fibers (fast-twitch, high energy) whereas muscles with predominantly type 1 fibers (slow-twitch, postural control) were less affected. This study provides valuable insight into muscle changes of MM patients during treatment, which might aid in tailoring exercise interventions more precisely to patients’ needs. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is characterized by a systemic inflammatory response and the expression of inflammatory factors in visceral adipose tissue (VAT). However, the association between these two inflammatory processes has not been fully elucidated. Therefore, this study aimed to (1) investigate whether whole blood counts, the neutrophil–lymphocyte ratio (NLR), the monocyte–lymphocyte ratio (MLR), serum adiponectin levels, and the mRNA expression of inflammatory genes (TLR2, TLR4, pro-inflammatory cytokines: IL-1β, IL-6, and TNF-α, anti-inflammatory cytokines: IL-1RA, IL-10, and adiponectin) in VAT are altered in women with GDM in comparison to pregnant women with normal glucose tolerance (NGT), and (2) determine the correlations between systemic and local VAT inflammation in all, GDM, and NGT women. Methods: Study of 50 GDM and 50 women with NGT with a cross-sectional design. Standard biochemical and hematological tests were conducted and relative mRNA expression in VAT was measured by RT-qPCR. Results: Women with GDM showed higher neutrophil, monocyte, NLR, MLR, and VAT TNF-α/IL-10 mRNA expression ratios while lymphocyte and eosinophil counts, serum adiponectin, and mRNA local VAT inflammatory markers such as TLR2, TLR4, IL-1β, IL-6, IL-1RA, and IL-10 were lower in women with GDM relative to women with NGT. Additionally, the circulating monocyte count were associated with TLR2 and TLR-4 VAT mRNA expression levels and eosinophils count were associated with IL-1β, IL-6, IL-10, and IL-1RA VAT expression levels in women with GDM. Conclusions: GDM is characterized by systemic inflammation, and some circulating immune cells, such as monocytes and eosinophils, are associated with the expression of inflammatory markers in VAT. Full article

Nucleic acid aptamers are single-stranded DNA or RNA molecules that can bind to a target with high specificity and affinity, as screened by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX). In recent years, SELEX technologies have been significantly advanced for the screening of aptamers for a variety of target molecules, cells, and even bacteria and viruses. By integrating recent advances of emerging technologies with SELEX, novel screening technologies for nucleic acid aptamers have emerged with improved screening efficiency, reduced production costs and enhanced aptamer performance for a wide range of applications in medical diagnostics, drug delivery, and environmental monitoring. Aptasensors utilize aptamers to detect a wide range of analytes, allowing for the accurate identification and determination of small molecules, proteins, and even whole cells with remarkable specificity and sensitivity. Further optimization of the aptasensor can be achieved by aptamer truncation, which not only maintains the high specificity and affinity of the aptamer binding with the target analytes, but also reduces the manufacturing cost. Predictive models also demonstrate the powerful capability of determination of the minimal functional sequences by simulation of aptamer–target interaction processes, thus effectively shortening the aptamer screening procedure and reducing the production costs. This paper summarizes the research progress of protein-targeted aptamer screening in recent years, introduces several typical aptasensors at present, discusses the optimization methods of aptasensors by combining efficient SELEX with advanced predictive algorithms or post-SELEX processes, as well as the challenges and opportunities faced by aptasensors. Full article

The main goal of this study was to consider the role of obesity/overweight as a potential modifier of associations between gene single nucleotide polymorphisms (SNPs) affecting the sex hormone-binding globulin level (SHBG_level) and uterine myoma (UM). In the two women cohorts differentiated by body mass index (BMI) (BMI ≥ 25, n = 782 [379 UM/403 control] and BMI < 25, n = 760 [190 UM/570 control]), the association of genome-wide association studies (GWAS)-correlated SHBG_level-tied nine loci with UM was studied by method logistic regression with a subsequent in-depth evaluation of the functionality of UM-causal loci and their strongly linked variants. BMI-conditioned differences in the associations of SHBG_level-tied loci with UM were revealed: in the BMI < 25 group, a variant rs17496332 (A/G) PRMT6 was UM-correlated (OR = 0.70; p_perm = 0.024), and in the BMI ≥ 25 cohort, a SNP rs3779195 (T/A) BAIAP2L1 was UM-associated (OR = 1.53; p_perm = 0.019). Both the UM-causal loci and their proxy SNPs have pronounced probable functionality in the organism as a whole, as well as in the liver (the SHBG synthesis place), adipose tissue, uterus, etc., thereby influencing significant processes for UM biology such as regulation of the gene transcription, embryogenesis/development, cell proliferation/differentiation/apoptosis, metabolism, lipid exchange, etc. In conclusion, the results of our work demonstrated, for the first time, the essential role of obesity/overweight as a meaningful modifier of associations between SHBG_level-tied polymorphisms and UM. Full article

Background/Objectives: The X-inactivation specific transcript (XIST) is a long noncoding RNA playing a crucial regulatory role in X chromosome inactivation (XCI)—a transcriptional regulatory process that silences one of the two X chromosomes in females to ensure proper dosage compensation between male and female mammals. The transcription of XIST is maintained throughout a female’s lifespan in all somatic cells, where XIST RNA binds to the X chromosome in cis and ensures chromosome-wide gene silencing. Disrupting XIST expression can lead to transcriptional reactivation of X-linked genes and epigenetic changes affecting cell development. The prevalence of XIST regulatory effects on mammalian transcription, however, remains unclarified. Methods: Here we performed a comparative expression analysis using RNA-sequencing datasets from recently published studies and examined the consequences of XIST-deletion on transcription at the whole genome, individual chromosome, and specific gene levels. We investigated the common differentially expressed genes (DEGs) and biological pathways following XIST loss across cell types, together with differential transcriptional analysis comparing the X chromosome and autosomes using cumulative distribution fractions. We analyzed the distribution of DEGs along the X chromosome with scatterplots and correlation analysis incorporating gene density and transposable elements. Results: Our findings indicate that the loss of XIST causes transcriptional changes in the X chromosome and autosomes that differ depending on cell type and state. XIST-deletion results in differential expression of genes subject to XCI-silencing as well as genes escaping XCI. In all the cell types we analyzed, X-linked genes show differential expression across the entire X chromosome in a cluster-like pattern according to gene density and, in certain cell types, correlate strongly with short interspersed nuclear element (SINE) distributions. Conclusions: Our results demonstrate that transcriptional roles of XIST can be highly associated with cell state: stem cells have different transcriptional responses compared to differentiated cells following XIST loss. Full article

It is of great significance to analyze the molecular mechanism of rice response to heavy ion irradiation and to mine its key response genes for food security. In this study, the regression equation for the dose survival rate was constructed using heavy ion irradiation on rice pollen. Through an immunofluorescence experiment, it was found that DSBs induced by irradiation could be repaired quickly, but the repair of complex damage required more time. RNA-seq of irradiated pollen showed that the gene expression patterns at different time points were significantly different. A total of 5556 differentially expressed genes (DEGs) were screened out, and the number of DEGs decreased with time. DEGs were mainly involved in stress response, protein folding, DNA repair, and other damage response processes at 0–1 h. At 6 h, the cells turned to normal metabolism functions, such as organic synthesis and protein activity. Combined with weighted gene co-expression network analysis (WGCNA) and trend analysis, the key transcription factor OsERF110 was identified in response to heavy ion irradiation, which acts on the nucleus and cell membrane. A total of 45,680 OsERF110 binding peaks were identified by DNA affinity purification sequencing (DAP-seq) in the whole genome. When this method was combined with RNA sequencing (RNA-seq), 62 OsERF110 target genes were further screened. These target genes were involved in DNA repair, stress response, redox, metabolic regulation, and other processes, forming the OsERF110 mediated radiation response regulatory network. The results of this study provide a new target for rice mutation breeding and lay a theoretical foundation for radiation biology research. Full article

Vitamin D is converted to a steroid hormone by 25-hydroxylation in the liver and then by 1-hydroxylation in the kidney to produce the circulating hormone 1,25-dihydroxy vitamin D [1,25(OH₂D]. This hormone then functions in cells of the intestinal mucosa and in bone to maintain whole-body calcium homeostasis. Classical vitamin D deficiency thus results in defective calcium homeostasis. Yet vitamin D deficiency is often reported in people with various diseases not associated with whole-body calcium homeostasis. Because of these associations with vitamin D deficiency, clinical trials have been undertaken to determine whether raising vitamin D status could be an effective treatment for such diseases. However, the results of such clinical trials have largely been inconclusive. The steroidal autocrine or paracrine role of locally produced 1,25(OH)₂D in many nonrenal cells throughout the body is protective against a range of pathological changes. In vitamin D deficiency such protection becomes defective. A disease process may thus be initiated, and then progress, while vitamin D status is inadequate, as in the months of winter in temperate regions of the world. The subsequent correction of vitamin D deficiency may no longer be able to protect patients when the disease process has already become established. To maintain the many protective roles of vitamin D against disease, it is important that public health strategies aim to maintain adequate vitamin D status throughout the year. Full article

Background/Objectives: Leukoreduced low-titer group O whole blood (LTOWB) is a promising option for early transfusion in massive hemorrhages, by providing red blood cells (RBCs), plasma, and platelets in a single unit. This study aimed to assess the effects of pathogen reduction (PR) on the LTOWB quality and its suitability for emergency transfusions, including its post-thaw RBC usability. Methods: Whole blood from 24 donors was processed and analyzed over seven days, including post-thaw assessments. Hematological and coagulation parameters, along with atomic force microscopy, were used to assess the RBCs’ morphology, cytoskeletal integrity, and nanomechanical properties. Results: The PR reduced the leukocyte content while preserving platelet counts at the level of the control group. Although certain clotting factors, such as fibrinogen (p < 0.001) and factor VIII (p < 0.001), were diminished after the PR, thromboelastometry results remained within reference ranges, indicating a maintained hemostatic potential. Morphological changes in RBCs were observed, but the membrane elasticity remained stable throughout storage and after thawing, indicating preserved macromechanical properties essential for hemostasis. Conclusions: These findings demonstrate that LTOWB treated with partial a leukoreduction and PR maintains functional and structural integrity, supporting its potential utility as a safe and effective transfusion product for managing acute blood loss. Full article

The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase ‘EphA2’ and the protease ‘Furin’ are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 (FURIN and EPHA2 genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, p = 0.017, co-dominant model, and OR = 0.409, p = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, p = 0.031, co-dominant model, and OR = 3.62, p = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, p = 0.024), with advanced clinical stage in men (OR = 2.22, p = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, p = 0.009, and OR = 5.15, p = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, p = 0.027, overdominant model). Our study is the first to demonstrate that FURIN and EPHA2 germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations. Full article

Hemolysis, or the breakdown of red blood cells, observed in medical devices has been a significant concern for many years, particularly when mechanical stress on the cells is considered. This study focuses on evaluating extensional stresses in two configurations of the U.S. Food and Drug Administration (FDA) nozzle: the Gradual Cone (GC) and Sudden Contraction (SC) models. The nozzle geometries were created as 3D models using Ansys Fluent 18.2 and its pre-processing software ICEM CFD. The mesh was constructed with hexahedral elements with O-grid topologies. Effects of varying flow conditions were observed by modeling five experimental cases of the FDA nozzles, including throat Reynolds numbers of 500, 2000, 3500, 5000, and 6500. Hemolysis potentials of FDA nozzle configurations were examined by analyzing the whole domains. Turbulent modeling was used by applying the shear stress transport k-ω (SST k-ω) model. A threshold of 2.8 Pa for extensional stress was observed. Moreover, the most commonly used power law models were applied to the FDA nozzle to see the effect of extensional stress on power law models. Zhang’s power law models gave the lowest standard error, while Giersiepen’s model gave the highest error on hemolysis predictions. Full article

Opuntia stricta var. dillenii (OPD) fruits are rich in betalains and phenolic compounds, which are recognized for their potential health-promoting properties. This study focuses on the optimization of pulsed electric field (PEF)-assisted solid–liquid green extraction (SLE) from OPD whole fruit, using response surface methodology (RSM) experimental design to obtain green extracts rich in bioactive compounds. The optimal PEF pre-treatment conditions (electric field strength and energy input) were determined based on the cell disintegration index (Zp), followed by optimizing SLE conditions (temperature, time, and ethanol content). High-performance liquid chromatography (HPLC-DAD-ESI-Qtof) was used to characterize the individual bioactive compound profile of the obtained OPD green extracts. Results showed that optimal PEF pre-treatment conditions were at 10.5 kJ/kg and 5 kV/cm, followed by SLE at 35 °C for 165 min, using water as the solvent. Conventional optimal SLE conducted at 45 °C, 8% ethanol, and 128 min was applied as the control process. The combined PEF-assisted SLE process enhanced total betalain and phenolic compound yields by 61% and 135%, respectively. Antioxidant activities (DPPH by 145%, FRAP by 28%) and anti-inflammatory potential (hyaluronidase inhibition by 19%) were also significantly improved. This study underscores the potential use of a PEF pre-treatment to improve obtaining green extracts rich in bioactive compounds with high biological activities from OPD whole fruits, using water as a solvent. Full article