Biomarkers Research Articles

Association Between the Atherogenic Index of Plasma and 90-Day Clinical Prognosis in Patients with Acute Pontine Infarction: A Single Center Study.

The atherogenic index of plasma (AIP) is a biomarker for coronary heart disease, atherosclerosis, and metabolic syndrome. However, the mechanism of its action in the acute phase of acute pontine infarction remains unclear. This study investigated the association between the AIP and the short-term prognosis of acute pontine infarction. Clinical and laboratory index data of patients admitted to the hospital for acute pontine infarction were continuously included, and these patients were followed up for 90 days after disease onset. The modified Rankin Scale (mRS) was used to evaluate the 90-day clinical outcomes of the patients, and an mRS score ≥3 was used to define adverse functional outcomes. Univariate analysis was used to detect differences in the indicators between the two groups. Patients were then divided into three groups according to the quantile of the AIP (T1: AIP ≤ 0.029; T2, 0.029 < AIP ≤ 0.248; T3, AIP > 0.248), and a binary logistic regression model was used to assess risk factors for prognosis shortly after acute pontine infarction. A total of 260 patients with acute pontine infarction (mean age=64.5±11.8 years) were included during the study period, and 68 (26.2%) patients had a poor 90-day prognosis. The AIP in the poor 90-day prognosis group was significantly greater (P <0.05) than that in the good 90-day prognosis group. The multivariate logistic regression analysis revealed that the AIP (OR=9.829; 95% CI: 2.837-34.051; p < 0.001), baseline NIHSS score (OR=1.663; 95% CI: 1.400-1.975; p < 0.001) and infarct volume (OR=1.762; 95% CI: 1.013-3.062; p=0.045) were significantly associated with poor 90-day prognosis in patients with acute pontine infarction. In patients with acute pontine infarction, the AIP may serve as an important biological marker of poor clinical prognosis and is independently associated with poor 90-day prognosis.

Distinct brain network patterns in complete and incomplete spinal cord injury patients based on graph theory analysis.

To compare the changes in brain network topological properties and structure-function coupling in patients with complete spinal cord injury (CSCI) and incomplete spinal cord injury (ICSCI), to unveil the potential neurobiological mechanisms underlying the different effects of CSCI and ICSCI on brain networks and identify objective neurobiological markers to differentiate between CSCI and ICSCI patients. Thirty-five SCI patients (20 CSCI and 15 ICSCI) and 32 healthy controls (HCs) were included in the study. Here, networks were constructed using resting-state functional magnetic resonance imaging to analyze functional connectivity (FC) and diffusion tensor imaging for structural connectivity (SC). Then, graph theory analysis was used to examine SC and FC networks, as well as to estimate SC-FC coupling values. Compared with HCs, CSCI patients showed increased path length (Lp), decreased global efficiency (Eg), and local efficiency (Eloc) in SC. For FC, ICSCI patients exhibited increased small-worldness, clustering coefficient (Cp), normalized clustering coefficient, and Eloc. Also, ICSCI patients showed increased Cp and Eloc than CSCI patients. Additionally, ICSCI patients had reduced SC-FC coupling values compared to HCs. Moreover, in CSCI patients, the SC network's Lp and Eg values were significantly correlated with motor scores, while in ICSCI patients, the FC network's Cp, Eloc, and SC-FC coupling values were related to sensory/motor scores. These results suggest that CSCI patients are characterized by decreased efficiency in the SC network, while ICSCI patients are distinguished by increased local connections and SC-FC decoupling. Moreover, the differences in network metrics between CSCI and ICSCI patients could serve as objective biological markers, providing a basis for diagnosis and treatment strategies.

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.

Enhancing early detection of pancreatic cancer by integrating AI with advanced imaging techniques

Pancreatic cancer remains one of the most lethal malignancies, with a five-year survival rate of less than 10%, primarily due to late-stage diagnosis and rapid disease progression. Early detection is critical for improving patient outcomes, yet current diagnostic methods lack the sensitivity and specificity needed for effective screening. This review explores the integration of advanced imaging techniques with artificial intelligence (AI) to enhance the early detection of pancreatic cancer. Emphasizing a biological approach, we examine the underlying molecular and cellular mechanisms that contribute to the pathogenesis of pancreatic cancer and how they manifest in imaging data. Key imaging modalities, including high-resolution magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), are evaluated for their efficacy in visualizing pancreatic abnormalities. AI algorithms, particularly machine learning and deep learning, are discussed in the context of their ability to analyze complex imaging datasets, identify subtle biomarkers, and predict disease onset with high accuracy. We delve into the biological markers that AI algorithms can detect, such as changes in the tumor microenvironment, alterations in tissue architecture, and specific molecular signatures of pancreatic ductal adenocarcinoma (PDAC). Furthermore, the integration of AI with molecular imaging techniques, such as positron emission tomography-magnetic resonance imaging (PET-MRI) and optical coherence tomography (OCT), is explored to provide a multi-faceted approach to early diagnosis. The review also highlights the potential of combining AI-driven imaging with liquid biopsies and genomics to create a comprehensive diagnostic framework. By leveraging the power of AI to interpret complex biological data, we propose a novel paradigm for the early detection of pancreatic cancer, aiming to improve screening protocols, enable timely therapeutic interventions, and ultimately enhance patient survival rates. In supposition, the integration of AI with advanced imaging techniques holds significant promise for revolutionizing the early detection of pancreatic cancer. Continued research and clinical validation are essential to translate these technological advancements into routine clinical practice, offering hope for better prognostic outcomes in patients with this devastating disease.

The circadian rhythm: A key variable in aging?

The determination of age-related transcriptional changes may contribute to the understanding of health and life expectancy. The broad application of results from age cohorts may have limitations. Altering sample sizes per time point or sex, using a single mouse strain or tissue, a limited number of replicates, or omitting the middle of life can bias the surveys. To achieve higher general validity and to identify less distinctive players, bulk RNA sequencing of a mouse cohort, including seven organs of two strains from both sexes of 5 ages, was performed. Machine learning by bootstrapped variable importance and selection methodology (Boruta) was used to identify common aging features where the circadian rhythms (CiR) transcripts appear as promising age markers in an unsupervised analysis. Pathways of 11 numerically analyzed local network clusters were affected and classified into four major gene expression profiles, whereby CiR and proteostasis candidates were particularly conspicuous with partially opposing changes. In a data-based interaction association network, the CiR-proteostasis axis occupies an exposed central position, highlighting its relevance. The computation of 11,830 individual transcript associations provides potential superordinate contributors, such as hormones, to age-related changes, as in CiR. In hormone-sensitive LNCaP cells, short-term supraphysiologic levels of the sex hormones dihydrotestosterone or estradiol increase the expression of the CiR transcript Bhlhe40 and the associated senescence regulator Cdkn2b (p15). According to these findings, the bilateral dysregulation of CiR appears as a fundamental protagonist of aging, whose transcripts could serve as a biological marker and its restoration as a therapeutic opportunity.

Identification and validation of ferroptosis related markers in erythrocyte differentiation of umbilical cord blood-derived CD34+ cell by bioinformatic analysis.

Ferroptosis has been observed to play an important role during erythrocyte differentiation (ED). However, the biological gene markers and ferroptosis mechanisms in ED remain unknown. We downloaded the datasets of ED in human umbilical cord blood-derived CD34+ cells from the Gene Expression Omnibus database. Using median differentiation time, the sample was categorized into long and short groups. The differentially expressed ferroptosis-related genes (DE-FRGs) were screened using differential expression analysis. The enrichment analyses and a protein-protein interaction (PPI) network were conducted. To predict the ED stage, a logistic regression model was constructed using the least absolute shrinkage and selection operator (LASSO). Overall, 22 DE-FRGs were identified. Ferroptosis-related pathways were enriched using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Gene Set Enrichment Analysis and Gene Set Variation Analysis revealed the primary involvement of DE-FRGs in JAK-STAT, MAPK, PI3K-AKT-mTORC1, WNT, and NOTCH signaling pathways. Ten-hub DE-FRGs were obtained using PPI analysis. Furthermore, we constructed mRNA-microRNA (miRNA) and mRNA-transcription factor networks. Immune cell infiltration levels differed significantly during ED. LASSO regression analysis established a signature using six DE-FRGs (ATF3, CDH2, CHAC1, DDR2, DPP4, and GDF15) related to the ED stage. Bioinformatic analyses identified ferroptosis-associated genes during ED, which were further validated. Overall, we identified ferroptosis-related genes to predict their correlations in ED. Exploring the underlying mechanisms of ferroptosis may help us better understand pathophysiological changes in ED and provide new evidence for clinical transformation.

Cranial fluctuating asymmetry and its relationship with non-specific physiological stress indicators in a contemporary South African cadaveric skeletal sample

ObjectivesBiological anthropologists frequently explore skeletal asymmetry, together with population health and disease. Given the conflicting findings in existing literature, this study aimed to clarify whether an association exists in a South African sample. MaterialsDry bone and cranial micro-focus X-ray Computed Tomography (micro-XCT) scans of 115 South African individuals were assessed. MethodsFluctuating asymmetry (FA) indices were calculated from interlandmark distances, and the frequency of four types of non-specific signs of physiological stress were documented to explore the relationship between FA and disease. ResultsBlack South Africans did not exhibit a high FA index; however, they had the highest prevalence of non-specific signs of physiological stress. However, no significant correlations were detected between FA indices and pathological lesions. ConclusionNo correlation was observed between FA and populations from different socio-economic backgrounds. However, individuals of lower socio-economic status (SES) demonstrated a greater prevalence of non-specific signs of physiological stress. SignificanceThis research suggests that skeletal indicators of stress may be a suitable biological marker for assessing differences in SES among population groups, while indicating that levels of cranial FA is an inadequate biological marker. LimitationsPossible limitations may include measurement error, and the lack of information on the life history and medical records of individuals in this sample. Suggestions for further researchFuture research should include a larger sample with more South African groups, and should evaluate the potential association among age, FA, and expression of skeletal markers of disease.

FGF-21 Level is higher in patients with breast cancer, a candidate for a new biomarker?

Aims: Fibroblast Growth Factor 21 (FGF-21) is a member of the FGF family involved in biological processes such as embryonic development. cell growth. morphogenesis. tissue repair. tumour growth and invasion. with mitogenic and cytogenetic activity at 19q13.33.Breast cancer is a deadly and increasing disease in women. and recent studies have shown a relationship between some cancers. including breast cancer. and hormones secreted from adipose tissue.The aim of the present study was the measurement of FGF-21 levels in patients with breast cancer and its association with breast cancer. Methods: The study included 39 patients with newly diagnosed breast cancer and 39 healthy controls. During the patients’ routine blood tests. a venous blood sample was taken and the serum levels of FGF-21 were determined by ELISA. Results: Demographic and laboratory data were compared between the newly diagnosed breast cancer group and the control group. The control group consisted of 39 participants with a mean age of 52.49 ± 7.02 years. In the patient group. 39 participants with a mean age of 52.15 ± 6.21 years were included in the study. there was no statistical difference regarding age(p&gt;0.05).In the control group. the mean FGF-21 level was 121.35 ± 88.4 pg/ml. while the mean FGF-21 level in the patient group was 171 ± 117.45 pg/ml. a statistically significant difference was detected(p value=0.036). Conclusion: FGF-21 is thought to have significant and beneficial effects on glucose. lipid and energy metabolism. as well as slowing the growth of cancer cells. and may later be used as a biological marker for breast cancer.

Telehealth Parenting Program and Salivary Epigenetic Biomarkers in Preschool Children With Developmental Delay

Children with developmental delays are at a heightened risk of experiencing mental health challenges, and this risk is exacerbated among racially minoritized children who face disproportionate adversity. Understanding the impact of parenting interventions on biological markers associated with these risks is crucial for mitigating long-term health disparities. To examine the effect of 20 weeks of an internet-based parent-child interaction training (iPCIT) program on biomarkers associated with aging and chronic inflammation among preschoolers with developmental delay at 12-month follow-up. An observational secondary analysis of data from a randomized clinical trial conducted from March 17, 2016, to December 15, 2020, to assess changes in salivary DNA methylation (DNAm)-derived biomarkers following iPCIT intervention. Participants were recruited from 3 Part C early intervention sites in a large southeastern US city. Eligible participants included children recruited within 3 months of their third birthday who had a Child Behavior Checklist Externalizing Problems T score greater than 60 and provided saliva in at least 1 study wave. Data analysis was conducted May 2023 to April 2024. Participants received either iPCIT (a telehealth therapeutic intervention focused on enhancing the parent-child relationship and addressing behavioral challenges in young children) or referrals as usual. DNAm at the 12-month follow-up was assessed using the Infinium HumanMethylationEPIC Bead Chip Assay to derive biomarkers DunedinPACE, C-reactive protein (CRP), and interleukin-6 (IL-6). Analyses were intent-to-treat and used path analysis. A total of 71 children (mean [SD] age, 36.27 [0.61] months 51 male [71.8%] and 20 female [28.2%]) were analyzed, of whom 34 received iPCIT and 37 received referrals as usual. The iPCIT group had a slower pace of aging (β = 0.26; 95% CI, 0.06 to 0.50; P = .03) and less DNAm-derived CRP (β = 0.27; 95% CI, 0.05 to 0.49; P = .01) relative to the control condition at the 12-month follow-up. These associations remained significant after accounting for baseline DNAm score, child demographics, and symptom severity, and were independent of predicted buccal epithelial cell proportion for both DunedinPACE and CRP. There was no association with DNAm-derived IL-6 (β = 0.14; 95% CI, -0.08 to 0.36; P = .21). In this study of a parenting intervention, iPCIT, the association of intervention with decreased molecular markers of inflammation and biological aging suggests their potential to modify aspects of the biological embedding of stress. Understanding the systemic biological impact of such interventions offers insights into addressing health disparities and promoting resilience among vulnerable populations. ClinicalTrials.gov Identifier: NCT03260816.

Opioid free analgesia after return home in ambulatory colonic surgery patients: a single-center observational study

BackgroundBecause of the adverse effects of morphine and its derivatives, non-opioid analgesia procedures are proposed after outpatient surgery. Without opioids, the ability to provide quality analgesia after the patient returns home may be questioned. We examined whether an opioid-free strategy could ensure satisfactory analgesia after ambulatory laparoscopic colectomy.MethodsWe performed a retrospective observational single-center study (of prospective collected database) including all patients eligible for scheduled outpatient colectomy. Postoperative analgesia was provided by paracetamol and nefopam. Postoperative follow-up included pain at mobilization (assessed by a numerical rating scale, NRS), hemodynamic variables, temperature, resumption of transit and biological markers of postoperative inflammation. The primary outcome was the proportion of patients with moderate to severe pain (NRS > 4) the day after surgery.ResultsData from 144 patients were analyzed. The majority were men aged 59 ± 12 years with a mean BMI of 27 [25-30] kg/m2. ASA scores were 1 for 14%, 2 for 59% and 3 for 27% of patients. Forty-seven patients (33%) underwent surgery for cancer, 94 for sigmoiditis (65%) and 3 (2%) for another colonic pathology. Postoperative pain was affected by time since surgery (Q3 = 52.4,p < 0.001) and decreased significantly from day to day. The incidence of moderate to severe pain at mobilization (NRS > 4) on the first day after surgery was (0.19; 95% CI, 0.13–0.27).ConclusionNon-opioid analgesia after ambulatory laparoscopic colectomy seems efficient to ensure adequate analgesia. This therapeutic strategy makes it possible to avoid the adverse effects of opioids.Trial registrationThe study was retrospectively registered and approved by the relevant institutional review board (CERAR) reference IRB 00010254–2018 – 188). All patients gave written informed consent for analysis of their data. The anonymous database was declared to the French Data Protection Authority (CNIL) (reference 221 2976 v0 of April 12, 2019).

Glycosylated Hemoglobin (HbA1C) as a Predictor of Early Postoperative Outcomes After Coronary Artery Bypass Grafting: A Single-Center Observational Study.

Background Diabetic patients present a majority of patients undergoing surgical revascularization. Hyperglycemia is associated with increased adverse events. Glycosylated hemoglobin (HbA1c) is an effective biological marker for long-term glycemic control. As a result, there is an increased trend in its use as a predictor of adverse outcomes. This study aims to assess the impact of elevated HbA1c on the occurrence of postoperative complications after coronary artery bypass grafting (CABG). Methods We conducted a retrospective review of medical records from January 2015 to December 2022 for adult patients who underwent isolatedCABG. We assessed patient demographics, medication, laboratory results, HbA1c results, and clinical data. The separate statistical models were designed to assess the predictors for thedevelopment of postoperative complications. Results This retrospective single-center study was conducted on 289 consecutive adult patients who underwent on-pump CABG. Patient demographics showed that uncontrolled HbA1c was more in females (p=0.022), and hemodialysis patients (p=0.018). Across different levels of HbA1C, there were no significant differences in terms of the incidence of postoperative complications(p=0.788 for infection, p=0.372 for the need for blood transfusion, p=0.721 for heart failure, p=0.692 for arrhythmia, and p=0.712 for death). HbA1c had no predictive value for postoperative complications as indicated by multivariate and stepwise analysis in a separate model for each complicationwith receiver operator characteristics curves of each model showing similar strength of both multivariate and stepwise models. Conclusions In our data, elevated preoperative HbA1c had no predictive value for early complications and intermediate postoperative outcomes. We recommend that surgery should proceed without delay, even if patients have elevated HbA1C levels. As for elective patients with low-risk features and anatomy, optimizing preoperative glycemic control can be considered.

Overexpressing miR-222-3p in cultured &lt;i&gt;Mycobacterium Tuberculosis&lt;/i&gt;-infected macrophages does not affect their bacteriostatic activity

Tuberculosis, a disease caused by the bacterium Mycobacterium tuberculosis, is a major public health concern. Innate and adaptive immunity provide robust defense against pathogens. However, M. tuberculosis, which co-evolved with humans, has acquired many mechanisms to evade the immune response and ensure its intracellular existence and long-term survival within the host. Moreover, emerging evidence suggests that this secretive bacterium can alter expression of regulatory noncoding RNAs (including microRNAs), leading to dysregulation of biological processes underlying tuberculosis pathogenesis. For example, miR-222-3p has been shown to regulate the functional reprogramming of macrophages and is involved in the regulation of host innate immunity. Previously, we demonstrated the important role of miR-222-3p as a biological marker of tuberculosis activity. To confirm their biological targets and understand their role in the pathogenesis of tuberculosis, many research groups are working to establish functional relationships between miRNA expression under different conditions and their actual biological action using molecular biology and bioinformatics methods. In the present study, we demonstrated the effect of miR-222-3p overexpression on several functions of human macrophages of monocytic origin activated with M. tuberculosis antigens in in vitro culture. Specifically, we found that miR-222-3p overexpression significantly decreased IL-6 and IFNγ expression and increased IL-1β and cxcl10 expression in cultures of uninfected macrophages. Infected macrophages overexpressing miR-222-3p were characterized by increased NF-κB and IL-6 expression, as were infected macrophages without transfection. Another important finding was that miR-222-3p overexpression caused a small but significant increase in reactive nitrogen species production by infected macrophages, but did not affect their bacteriostatic activity against M. tuberculosis. Elucidating the functions of different microRNAs in regulating different pathogenic pathways in TB may lead to discovering new therapeutic targets. The detailed study of microRNAs that regulate immune-associated pathways will be useful for the design of miRNA mimetic molecules, either as inhibitors or as activators. Immune effects induced by miRNA drugs are currently a major challenge for miRNA therapeutics.

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls

BackgroundAdenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles.ResultsDifferences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse.ConclusionsThe vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Over-commitment positively predicts hair cortisol concentrations only in nurses with high need for recovery.

In the contemporary workplace, enduring fatigue has become a standard for employees. This investigation assesses whether such working conditions exacerbate the depletion of employees' personal resources. The need for recovery serves as an indicator of the necessity to mitigate post-work fatigue. A high need for recovery signifies that employees must commence a new workday while already fatigued. This research recruited two cohorts of nurses, categorized by a high need for recovery and a low need for recovery, to examine the correlation between work effort and hair cortisol concentrations in each group. Hair cortisol concentrations serve as a biological marker of cumulative cortisol secretion over a specific time frame, reflecting overall personal resource expenditure during this interval. Findings revealed a notable positive correlation between intrinsic work effort (over-commitment) and hair cortisol levels exclusively among nurses with a high need for recovery. These outcomes imply that active effort amidst fatigue may lead to excessive strain. This insight enriches the classic 'effort-recovery' model by illustrating how an employee' s personal volition can influence the accumulation of fatigue.

À propos du diagnostic préimplantatoire des aneuploïdies (DPI-A). Les inconvénients de mots inappropriés et d’une réglementation inadaptée

Finding biological markers to assess the ability of embryos to develop is a major objective of research being carried out to improve the results of in vitro fertilization (IVF). Among these markers, the chromosomal content of embryonic cells has been the subject of numerous studies to identify euploid embryos which will be transferred as a priority into the uterus. In France, a clinical research program funded by the Ministry of Health was undertaken to evaluate the benefit of this strategy when IVF is carried out in women aged 35 to 41. This program was interrupted because its authorization was canceled by a court on the grounds that the search for aneuploidy in the embryo is a preimplantation genetic diagnosis (PGD) and that this type of analysis is not provided for in the governing law. The law says in fact that a PGD can only be carried out if “has been previously and precisely identified, in one of the parents or one of their immediate ascendants in the case of a seriously disabling illness, with late revelation and prematurely endangering the vital prognosis”. But the chromosomal analysis provided for in the research protocol is not a diagnosis, it is a test which identifies the embryos most capable of developing. Like all other techniques with the same goal, this test is not the responsibility of the law but of the good practice guide. Studies seeking to improve the results of IVF for the benefit of couples who use it should not be prevented.

Experimental confirmation and bioinformatics reveal biomarkers of immune system infiltration and hypertrophy ligamentum flavum.

Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended. The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum. The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting. Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine-cytokine receptor interaction, and TGF-β signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group. The TGF-β signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.

SARS-CoV-2 RNA Detection in Wastewater and Its Effective Correlation with Clinical Data during the Outbreak of COVID-19 in Salamanca.

Wastewater treatment plants (WWTPs) are the final stage of the anthropogenic water cycle where a wide range of chemical and biological markers of human activity can be found. In COVID-19 disease contexts, wastewater surveillance has been used to infer community trends based on viral abundance and SARS-CoV-2 RNA variant composition, which has served to anticipate and establish appropriate protocols to prevent potential viral outbreaks. Numerous studies worldwide have provided reliable and robust tools to detect and quantify SARS-CoV-2 RNA in wastewater, although due to the high dilution and degradation rate of the viral RNA in such samples, the detection limit of the pathogen has been a bottleneck for the proposed protocols so far. The current work provides a comprehensive and systematic study of the different parameters that may affect the detection of SARS-CoV-2 RNA in wastewater and hinder its quantification. The results obtained using synthetic viral RNA as a template allow us to consider that 10 genome copies per µL is the minimum RNA concentration that provides reliable and consistent values for the quantification of SARS-CoV-2 RNA. RT-qPCR analysis of wastewater samples collected at the WWTP in Salamanca (western Spain) and at six pumping stations in the city showed that below this threshold, positive results must be confirmed by sequencing to identify the specific viral sequence. This allowed us to find correlations between the SARS-CoV-2 RNA levels found in wastewater and the COVID-19 clinical data reported by health authorities. The close match between environmental and clinical data from the Salamanca case study has been confirmed by similar experimental approaches in four other cities in the same region. The present methodological approach reinforces the usefulness of wastewater-based epidemiology (WBE) studies in the face of future pandemic outbreaks.

SODIUM NITRITE (E250) AND ZINC AS MODULATORS OF THE BIOMECHANICAL PROPERTIES OF BLOOD IN SPORTS

Nutritional supplements are often used by athletes to support their performance. However, if there is no nutrient deficiency, supplementation may not improve performance and may even have a detrimental effect on both performance and health. The aim of this study was to review the influence of sodium nitrite (NaNO2) and zinc (Zn) on the hemorheological status of different types of blood cells with application in sports. Sodium nitrite, known as food preservative E250, and zinc are proven modulators of the biomechanical properties of blood, influencing its hematometric and hemorheological properties. Our previous experimental results demonstrated that intraperitoneal injection of NaNO2 in mature rats had a diverse effect on the leukocyte and platelet populations. After the treatment, the number of monocytes and granulocytes decreased significantly, thus increasing the susceptibility to infections. The number of platelets increased, altering the coagulation status of blood. Scientific research data show that the proper intake of NaNO2 and Zn improves glucose metabolism, a key factor in maintaining energy levels during physical activity, muscle strength, and endurance. Zn also exhibits protective effects against bone loss. Excessive intake of zinc for long periods may interfere with other essential elements of metabolism. This review proves that hemorheological parameters such as whole blood viscosity, plasma viscosity, as well as the main hematometric indices are suitable quantitative biological markers for monitoring nitrite and/or zinc supplementation.

Urinary Extracellular Vesicles as a Readily Available Biomarker Source: A Simplified Stratification Method.

Urine, a common source of biological markers in biomedical research and clinical diagnosis, has recently generated a new wave of interest. It has recently become a focus of study due to the presence of its content of extracellular vesicles (EVs). These uEVs have been found to reflect physiological and pathological conditions in kidney, urothelial, and prostate tissue and can illustrate further molecular processes, leading to a rapid expansion of research in this field In this work, we present the advantages of an immunoaffinity-based method for uEVs' isolation with respect to the gold standard purification approach performed by differential ultracentrifugation [in terms of purity and antigen presence. The immunoaffinity method was made feasible by combining specific antibodies with a functionalized polymethacrylate polymer. Flow cytometry indicated a significant fluorescence shift, validating the presence of the markers (CD9, CD63, CD81) and confirming the effectiveness of the isolation method. Microscopy evaluations have shown that the morphology of the vesicles remained intact and corresponded to the expected shapes and dimensions of uEVs. The described protocol is inexpensive, fast, easy to process, has good reproducibility, and can be applied to further biological samples.

Trioxidized cysteine and aging: a molecular binomial that extends far beyond classical proteinopathic paradigms.

Increased oxidative stress (OS) and the disruption of the equilibrium between the production of reactive oxygen species and antioxidants are key molecular features of unhealthy aging. OS results in the formation of oxidative posttranslational modifications (PTMs), some of which involve cysteine (Cys) residues in aging proteomes, and specifically, the formation of trioxidized Cys (t-Cys), which leads to permanent protein damage. Recent findings in rodents have uncovered that irregular regulation of t-Cys residues in the aging proteome disrupts homeostatic phosphorylation signaling, resulting in alterations to proteins that are analogous to those caused by phosphorylated serine (p-Ser) residues. This work contextualizes these significant findings and discusses the implications and molecular role(s) of t-Cys in the aging proteome. Furthermore, we present novel data, validating the increase of specific t-Cys sites associated with aging in a blood-related circulating human proteome. The scope and findings included here support the hypothesis that t-Cys residues may serve as important mechanistic and biological markers, warranting further exploration in the context of unhealthy aging and age-related major diseases.