Related Biomarkers Research Articles

Immune checkpoint inhibitor therapy as a neoadjuvant treatment for muscle-invasive bladder carcinoma

Abstract Background and objectives Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma, and neoadjuvant immunotherapy is being extensively explored. This review highlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations. Materials and methods Relevant trials were retrieved from PubMed/MEDLINE and clinical trials databases. In addition, abstracts of major international oncology meetings (American Society of Clinical Oncology, American Association for Cancer Research, European Society of Medical Oncology, and European Council of Clinical Oncology) were reviewed until the European Society of Medical Oncology 2023 congress. The review also incorporated results from several exploratory investigations disclosed in recent years. Results This review focused on neoadjuvant immune checkpoint inhibitor monotherapy, combination therapy, and clinical biomarkers in relation to cisplatin-based chemotherapy tolerance. Most available literature consists of clinical investigations involving small sample, single-arm Phase II trials, with the primary endpoint being the pathologic complete response rate. The preliminary results from these studies are promising, demonstrating stage reduction rates comparable to or even exceeding those of standard chemotherapy, without compromising subsequent radical cystectomy. Conclusions Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy. However, these findings require confirmation in large Phase III clinical trials, with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.

Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury - a Prospective Cohort Study.

Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis. This study evaluates suPAR and related neuroinflammatory biomarkers in serum for brain injury prognosis. This prospective study included 31 aSAH, 30 IS, 13 TBI, and three healthy controls (n = 77). Serum samples were collected on average 5.9days post-injury, analyzing suPAR, IL-1β, cyclophilin A, and TNFα levels using ELISA. Outcomes were assessed 90days post-injury with the modified Rankin Scale (mRS), categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Statistical analyses included 2-tailed t-tests, Pearson's correlations, and machine learning linear discriminant analysis (LDA) for biomarker combinations. Elevated suPAR levels were found in brain injury patients compared to controls (p = 0.017). Increased suPAR correlated with unfavorable outcomes (p = 0.0018) and showed prognostic value (AUC = 0.66, p = 0.03). IL-1β levels were higher in the unfavorable group (p = 0.0015). LDA combinatory analysis resulted a fair prognostic accuracy with canonical equation = 0.775[suPAR] + 0.667[IL1-β] (AUC = 0.77, OR 0.296, sensitivity 93.1%, specificity 53.1%, p = 0.0007). No correlation was found between suPAR and CRP or infection status. Elevated suPAR levels in acute brain injury patients were associated with poorer outcomes, highlighting suPAR's potential as a prognostic biomarker across different brain injury types. Combining IL-1β with suPAR improved prognostic accuracy, supporting a multimodal biomarker approach for predicting outcomes.

Assessment of the dietary amino acid profiles and the relative biomarkers for amino acid balance in the low-protein diets for broiler chickens.

Research on low-protein-level diets has indicated that even though the profiles of essential amino acids (EAAs) follow the recommendation for a normal-protein-level diet, broilers fed low-protein diets failed to achieve productive performance compared to those fed normal diets. Therefore, it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance. Furthermore, identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology. In this study, 12 dietary treatments [Con(+), Con(-), L&A(-), L&A(+), M&C(-), M&C(+), BCAA (-), BCAA(+), Thr(-), Thr(+), Trp(-) and Trp(+)] were established by combining different EAAs including lysine and arginine, methionine and cysteine, branched-chain amino acid (BCAA), threonine, and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets. Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments, biomarkers associated with optimal and suboptimal amino acid balance were identified. Growth performance, carcass characteristics, hepatic enzyme activity, serum biochemical parameters, and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns. Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers. For the low-protein diet, the dietary concentrations of lysine, arginine, and tryptophan, but not of methionine, cystine, or threonine, needed to be increased. Therefore, further research on individual BCAA is required. For untargeted metabolomic analysis, Con(+) was selected as a normal diet (NP) while Con(-) represented a low-protein diet (LP). L&A(+) denotes a low-protein amino acid balanced diet (LPAB) and Thr(+) represents a low-protein amino acid imbalance diet (LPAI). The metabolites oxypurinol, pantothenic acid, and D-octopine in birds were significantly influenced by different dietary amino acid patterns. Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets. Oxypurinol, pantothenic acid, and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.

Abstract A075: Circulating T-cell receptor repertoire analysis improves cancer early detection

Abstract Introduction: Cancer screening by liquid biopsy promises to detect cancer early when it can be cured. However, current ctDNA-based approaches detect only a minority of early-stage cancers. For liquid biopsy to realize its full potential for cancer early detection, sensitivity for earliest stage disease must be improved. Methods: We set out to improve sensitivity of liquid biopsy by exploiting tumor recognition by T cells through sequencing of the circulating T-cell receptor repertoire. Using gDNA extracted from blood buffy coats, we studied a cohort of 471 lung cancer patients (85% stage I) and 600 subjects without cancer enriched for older individuals with a history of smoking. We performed TCR beta chain sequencing to yield a median of 101,899 TCR clonotypes per sample (median 81,602 cancer / 112,966 controls) and built a TCR sequence similarity graph to cluster clonotypes into TCR repertoire functional units (RFUs). The TCR frequencies of RFUs were tested for association with cancer status and significantly associated RFUs were combined using an SVM model into a cancer score. Cancer RFU levels were also correlated to imputed subject HLA types for 32 HLA Class I and 38 Class II alleles. The model was evaluated by 10-fold cross-validation and compared to a ctDNA panel of 237 mutation hotspots in 154 lung cancer driver genes and to 17 lung cancer related protein biomarkers in 86 subjects. Results: We identified 372 cancer-associated TCR RFUs at FDR≤0.1, including 198 enriched in cancer samples (fold-change range 1.03 to 3.13) and 174 enriched in controls (fold- change 0.96 to 0.30). Levels of 265/372 (71%) RFUs were correlated to presence of an HLA allele at FDR ≤ 0.1. Of the total 2,770 significant HLA-RFU associations, 479 (17%) involved an HLA Class I allele, while 2,291 (83%) involved an HLA Class II allele, highlighting a potential role for CD4 helper or regulatory T cell antigen recognition in the cancer RFUs found. The RFU cancer score achieved a cross-validated test ROC AUC of 0.71 for cancer status prediction (0.71 Stage I / 0.70 Stage II-IV) with 49% of Stage I cancers detected at a specificity of 80%. Importantly, the cancer score was not dependent on sample source site, technical or biological variation in TCR repertoire depth, or lung cancer histology subtype. The TCR RFU score also distinguished lung cancer patients from control subjects with other conditions such as benign lung nodules and COPD. We observed an up to ∼20%-point gain in sensitivity for stage I cancer when TCR RFUs were added to ctDNA and proteins in a potential multi-analyte cancer screening test. By contrast, TCR analysis did not provide additional sensitivity for stage II-IV disease. Conclusion: We demonstrate detection of a significant fraction of early lung cancer cases from blood by analyzing the circulating TCR repertoire and show that this signal is complementary to established analytes such as proteins and ctDNA. A similar study for the detection of early colorectal cancer and advanced adenomas is under way. Citation Format: Yilong Li, Michelle Nahas, Dennis Stephens, Kate Froburg, Emma Hintz, Devin Champagne, Amaneet Lochab, Markus Brown, Jasper Braun, María Antonia Fortuño, María-del-Mar Ocón, Andrea Pasquier, Inés María Luque, Christopher W. Seder, Jeffrey A. Borgia, Luis Miguel Seijo, Luis M Montuenga, Roman Yelensky. Circulating T-cell receptor repertoire analysis improves cancer early detection [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A075.

Milk metabolite profiling of dairy cows as influenced by mastitis

Mastitis is a disease with frequent incidence in dairy cows, causing huge financial losses to the dairy industry globally. The identification of certain biomarkers is crucial for the early diagnosis and management of mastitis. Metabolomics technology is a useful tool to accurately and efficiently analyze the changes of metabolites in biofluids in response to internal and external stimulations. Milk is the secreted by udder, and milk metabolites can directly reflect whether the udder are in the healthy or diseased state. The milk metabolomics analysis of mastitis can reveal the physiological and pathological changes of mammary gland and screen the related biomarkers, so as to offer useful reference for the prediction, diagnosis, and management of mastitis. Therefore, the aim of the present study was to comprehensively summarize milk metabolic change caused by naturally occurring or experimentally induced mastitis in dairy cows. In addition, comparative analysis and enrichment analysis were conducted to further discover potential biomarkers of mastitis and to identify the relevant pathways differentiating the healthy and mastitic cows. Multiple milk metabolites were identified to be altered during mastitis based on different metabolomics platforms. It was noteworthy that there were 28 metabolites not only identified by at least two different studies, but also showed consistent change tendency among the different studies. By comparison with literature, we further identified 12 milk metabolites, including acetate, arginine, β-hydroxybutyrate, carnitine, citrate, isoleucine, lactate, leucine, phenylalanine, proline, riboflavin, and valine that were linked with the occurrence of mastitis, which suggested that these 12 milk metabolites could be potential biomarkers of mastitis in dairy cows. Several pathways were revealed to explain the mechanisms of the variation of milk metabolites caused by mastitis, such as phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, riboflavin metabolism, and tricarboxylic acid (TCA) cycle. These results offer a further understanding for the alteration of milk metabolites caused by mastitis, which have a potential significance in the development of more reliable biomarkers for mastitic diagnosis in dairy cows.

The Role of Fatty Acid Metabolism, the Related Potential Biomarkers, and Targeted Therapeutic Strategies in Gastrointestinal Cancers.

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid-related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies.

Identification of metabolism related biomarkers in obesity based on adipose bioinformatics and machine learning

BackgroundObesity has emerged as a growing global public health concern over recent decades. Obesity prevalence exhibits substantial global variation, ranging from less than 5% in regions like China, Japan, and Africa to rates exceeding 75% in urban areas of Samoa.AimTo examine the involvement of metabolism-related genes.MethodsGene expression datasets GSE110729 and GSE205668 were accessed from the GEO database. DEGs between obese and lean groups were identified through DESeq2. Metabolism-related genes and pathways were detected using enrichment analysis, WGCNA, Random Forest, and XGBoost. The identified signature genes were validated by real-time quantitative PCR (qRT-PCR) in mouse models.ResultsA total of 389 genes exhibiting differential expression were discovered, showing significant enrichment in metabolic pathways, particularly in the propanoate metabolism pathway. The orangered4 module, which exhibited the highest correlation with propanoate metabolism, was identified using Weighted Correlation Network Analysis (WGCNA). By integrating the DEGs, WGCNA results, and machine learning methods, the identification of two metabolism-related genes, Storkhead Box 1 (STOX1), NACHT and WD repeat domain-containing protein 2(NWD2) was achieved. These signature genes successfully distinguished between obese and lean individuals. qRT-PCR analysis confirmed the downregulation of STOX1 and NWD2 in mouse models of obesity.ConclusionThis study has analyzed the available GEO dataset in order to identify novel factors associated with obesity metabolism and found that STOX1 and NWD2 may serve as diagnostic biomarkers.

Autologous platelet rich plasma injection can be effective in the management of osteoarthritis of the knee: impact on IL-1 β, TNF-α, hs-CRP

ObjectiveTo analyze the clinical efficacy of autologous platelet rich plasma (PRP) injection in the treatment of knee osteoarthritis (KOA) and its influence on related biomarkers such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP).Method150 study subjects are randomly selected from KOA patients received treatment in the Third Hospital of Bethune Hospital from January 2022 to January 2023. After enrollment, patients are randomly numbered 1–100. 75 patients with odd and even numbers are included in the control group and the observation group, respectively. The former is cured with etocoxib, while the latter is treated with autologous PRP injection based on this. The clinical efficacy, relevant biomarkers (IL-1β, TNF-α, hs-CRP), and Lysholm knee score scale and Fugl Meyer assessment (FMA) scores are compared and analyzed.ResultsThe total effective rate of 94.67% (71/75) in the observation group was higher than 84.00% (63/75) in the other one group (P < 0.05). Before treatment, the comparison in IL-1β, TNF-α, hs-CRP, Lysholm knee joint score, and FMA scale score are with P > 0.05. When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels within the group were lower than before treatment, while the Lysholm knee joint score and FMA scale score were higher than before treatment (P < 0.05). When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels and the Lysholm knee joint and FMA scale scores in the observation group were lower and higher than those in the other one group, respectively (P < 0.05).ConclusionThe application of autologous PRP injection therapy in KOA patients can significantly improve their levels of related biomarkers, effectively improve knee joint function and motor function, and have good clinical efficacy.

Neurophysiological markers of early cognitive decline in older adults: a mini-review of electroencephalography studies for precursors of dementia.

The early detection of cognitive decline in older adults is crucial for preventing dementia. This mini-review focuses on electroencephalography (EEG) markers of early dementia-related precursors, including subjective cognitive decline, subjective memory complaints, and cognitive frailty. We present recent findings from EEG analyses identifying high dementia risk in older adults, with an emphasis on conditions that precede mild cognitive impairment. We also cover event-related potentials, quantitative EEG markers, microstate analysis, and functional connectivity approaches. Moreover, we discuss the potential of these neurophysiological markers for the early detection of cognitive decline as well as their correlations with related biomarkers. The integration of EEG data with advanced artificial intelligence technologies also shows promise for predicting the trajectory of cognitive decline in neurodegenerative disorders. Although challenges remain in its standardization and clinical application, EEG-based approaches offer non-invasive, cost-effective methods for identifying individuals at risk of dementia, which may enable earlier interventions and personalized treatment strategies.

Relevance of the basophil activation test in a cohort of 240 patients with chronic spontaneous urticaria.

Basophil activation test (BAT) is considered to be the best biomarker to predict autoimmune chronic spontaneous urticaria (aiCSU). To date, few studies have investigated the utility of BAT in real-life clinical practice, the role of aiCSU biomarkers in relation to omalizumab therapy and the association between aiCSU tests. This study aimed to analyze the clinical and laboratory features of a prospective cohort with CSU according to their BAT status, as well as to study omalizumab efficacy according to aiCSU biomarkers. A prospective study was conducted from 2010 to 2024 in patients with CSU. BAT alongside other laboratory tests were performed, and clinical and therapeutic features were prospectively collected. Data obtained was compared according to BAT status. Furthermore, omalizumab drug survival was typified according to aiCSU biomarkers. A total of 240 patients were included in the study. BAT positive patients presented more frequently low IgE levels, higher occurrence of IgG anti-thyroid peroxidase (anti-TPO) positivity, autologous serum skin test (ASST) positivity, basopenia, and eosinopenia. The multivariate logistic regression revealed that ASST (OR:7.69, 95%CI: 2.81-21.0) and anti-TPO (OR:2.63, 95%CI: 1.05-6.61) were associated to BAT positivity. All aiCSU biomarkers (BAT, ASST, combined ASST/BAT positivity and low IgE/anti-TPO+) associated significantly shorter omalizumab survival due to failure. In the cohort, both low IgE/anti-TPO+ and ASST were concordant and associated to BAT. The use of BAT in clinical practice delineates a subgroup of patients with specific clinical, laboratory and therapeutic features, including increased omalizumab failure.

Mitophagy related diagnostic biomarkers for coronary in-stent restenosis identified using machine learning and bioinformatics

Percutaneous coronary intervention (PCI) combined with stent implantation is currently one of the most effective treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) significantly compromises its long-term efficacy. Mitophagy plays a crucial role in vascular homeostasis, yet its role in ISR remains unclear. This study aims to identify mitophagy-related biomarkers for ISR and explore their underlying molecular mechanisms. Through differential gene expression analysis between ISR and Control samples in the combined dataset, 169 differentially expressed genes (DEGs) were identified. Twenty-three differentially expressed mitophagy-related genes (DEMRGs) were identified by intersecting with mitophagy-related genes (MRGs) from the GeneCards, and functional enrichment analysis indicated their significant involvement in mitophagy-related biological processes. Using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Logistic-LASSO, RF, and SVM-RFE), LRRK2, and ANKRD13A were identified as mitophagy-related biomarkers for ISR. The nomogram based on these two genes also exhibited promising diagnostic performance for ISR. Gene Set Enrichment Analysis (GSEA) as well as immune infiltration analyses showed that these two genes were closely associated with immune and inflammatory responses in ISR. Furthermore, potential small molecule compounds with therapeutic implications for ISR were predicted using the connectivity Map (cMAP) database. This study systematically investigated mitophagy-related biomarkers for ISR and their potential biological functions, providing new insights into early diagnosis and precision treatment strategies for ISR.

Single and combined effects of phenanthrene and cadmium on oxidative stress and detoxification related biomarkers in clams (Meretrix meretrix)

Biomarkers concerning antioxidant reactions and detoxification metabolics were evaluated in Meretrix meretrix exposed to cadmium (Cd, 10 μg/L) and phenanthrene (PHE, 100 μg/L) individually and in combination (10 μg/L Cd + 100 μg/L PHE) for 7 days. The accumulation of Cd and PHE measured in the digestive gland, gill, mantle, and axe foot of the clam showed significant increase in combination treatment and it was higher than the single Cd or single PHE treatment. The activities of oxidative stress-related enzymes, the expression of Cu/Zn SOD, and the content of MDA increased after Cd and PHE exposure in the digestive gland and gill at most cases. In the digestive gland, CAT gene expression was significantly induced in Cd-single group and significantly inhibited in PHE-single group and Cd-PHE mixed group at both day 3 and day 7; in the gill, CAT gene expression was significantly inhibited in all groups at day 3 and except for Cd-single group at day 7. MT expression was significantly induced in Cd-single and Cd-PHE mixed groups at day 7, while hsp70 expression was significantly inhibited in PHE-single and Cd-PHE mixed groups at day 7. The results indicated that SOD, CAT, GST, MDA, Cu/Zn SOD, CAT, MT and hsp70 were sensitive to cadmium and PHE in a water environment, and can be used as indicators of marine heavy metal pollution.

B-147 Enhancing the Detection of Vitamin D Metabolites by LC-MS/MS Using a Novel Derivatization Kit

Abstract Background Vitamin D is crucial for various biological functions and exists in various tissues, including bones, intestines, and kidneys. 25-hydroxyvitamin D serves as a key marker for assessing vitamin D status in the body. Currently, LC-MS/MS is the gold standard for measuring vitamin D levels. The JeoQuant Kit for LC/MS Analysis of Vitamin D Metabolites (JEOL, Tokyo, Japan), which is used for the determination of vitamin D metabolites in serum based on the DAP-PA (Seki et al, 2019), enhances the ionization efficiency in the LC-MS/MS system for four vitamin D metabolites (25(OH)D3, 25(OH)D2, 24,25(OH)2D3 and 3-epi-25(OH)D3), enabling accurate fractionation and quantification. DAP-PA was developed as a caged Cookson-type reagent, demonstrating significantly enhanced stability compared to previous non-caged Cookson-type reagents. Our research aimed to assess whether the kit works practically. Methods The JeoQuant Kit contains internal standards of stable isotope-labelled compounds at appropriate concentrations, derivatization reagents, quality control materials derived from human serum and calibration materials. An Acquity H-Class UPLC coupled with an Acquity TQD mass spectrometer (Waters, MA, US) was used for analysis. CAPCELL CORE C18 2.1mm*100mm (Osaka-soda, Tokyo, Japan) was used as the analytical column. For the pretreatment, an Isolute SLE+ column (Biotage, Tokyo, Japan) was used. Eluent of LC-MS/MS was used 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile, with binary gradient. Results Using attached control L/H, reproducibility was shown by intra- and inter-assay CVs which were below 10% and 15%, respectively. Storage tests of derivatization agents at -20°C, 4°C, and room temperature for one week showed no significant difference on peak areas (one-way ANOVA). Through this derivatization, it was possible to achieve more than a 20-fold increase in sensitivity compared to measurements without derivatization. Notably, low concentrations of 3-epi-25(OH)D3 were distinctly separated and detected. Conclusions This study showed that the JeoQuant Kit effectively increases the sensitivity of vitamin D metabolites through derivatization. It also emphasized the reagent's notable stability. Furthermore, it enabled the detection of 3-epi-25(OH)D3 with less sensitive LC-MS/MS models, offering clear separation from 25(OH)D3. The kit, which is complete with calibrants, internal standards, and quality control samples, simplifies analytical procedures for vitamin D metabolite quantification, potentially aiding in developing Vitamin D- related biomarkers. Efforts to compare analytical performance of this kit with that of other methods are underway to establish its benefits.

The temporal dynamics of the gut mycobiome and its association with cardiometabolic health in a nationwide cohort of 12,641 Chinese adults

The dynamics of the gut mycobiome and its association with cardiometabolic health remain largely unexplored. Here, we employ internal transcribed spacer (ITS) sequencing to capture the gut mycobiome composition and dynamics within a nationwide human cohort of 12,641 Chinese participants, including 1,946 participants with repeated measurements across three years. We find that the gut mycobiome is associated with cardiometabolic diseases and related biomarkers in both cross-sectional and dynamic analyses. Fungal alpha diversity indices and 19 mycobiome genera are the major contributors to the mycobiome-cardiometabolic disease link. Particularly, Saccharomyces emerges as an effect modifier of traditional risk factors in promoting type 2 diabetes risk. Further integration of multi-omics data reveals key metabolites such as γ-linolenic acid and L-valine linking the gut mycobiome to type 2 diabetes. This study advances our understanding of the potential roles of the gut mycobiome in cardiometabolic health.

Grifola frondosa extract as a fetal bovine serum supplement for the culture of bovine muscle satellite cells under low serum conditions

Expensive fetal bovine serum (FBS) is a major obstacle to the production of cultivated meat. However, because FBS substitutes do not sufficiently induce cell proliferation, a good alternative is to reduce the amount of FBS and use ingestible additives to promote cell proliferation. In this study, Grifola frondosa extract (GFE) was used to investigate its potential as an additive to promote myogenesis of bovine muscle satellite cells from Hanwoo cattle under low serum conditions (10 % FBS). GFE treated with 10 % FBS only during the proliferation period not only increased cell proliferation and related biomarkers in a concentration-dependent manner (0.78–12.5 μg/mL), but also increased cell differentiation. Additionally, differentiation was promoted when cells were with GFE treated only during the differentiation period. Especially GFE at 12.5 µg/mL induced significantly higher proliferation and differentiation rates than 20 % FBS medium. In particular, compared to treatment alone in the proliferation or differentiation periods, GFE treatment in both periods contributed to an increase in the differentiation rate and significantly enhanced total protein production. The integration of GFE into cultivated meat production presents a promising approach to reducing FBS dependence, lowering costs, and enhancing scalability, aligning with sustainability and consumer acceptance goals.

Comparison between standard hematological parameters and blood doping biomarkers in dried blood spots within the athlete population of Swiss Sport Integrity.

The study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context. The aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, "DBS OFF-score". Ten athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards. Most athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu. In this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

New Insight in Using of Mesenchyme Stem Cell Conditioning Medium for the Impaired Muscle related Biomarkers: In vivo Study with Rat Model.

This study aimed to investigate the effects of Umbilical Cord Mesencymal Stem Cell Conditioning Medium (UC MSC-CM) administration on body weight recovery and the level of four molecular biomarkers, namely Superoxide Dismutase (SOD), vascular Endothelial Growth Factor (VEGF), C-Reactive Protein (CRP), and myostatin. Secretome was injected intramuscularly twice at 1.5 mL (day 7 and 14) into the right thigh of high-dose, short-term galactose-induced aging rats. The data of day 7 (before) and day 21 (after the administration) were evaluated. The body weights and the four biomarkers were measured before (day 7) and after intervention (day 21). This study showed that the UC MSC-CM intramuscular administrations did not influence body weight regeneration. However, it could increase SOD and VEGF levels and decrease CRP and myostatin levels. Treatment with UC MSC-CM is a promising and potential agent in treating sarcopenia.

Sarcopenia is a predictor for Alzheimer’s continuum and related clinical outcomes

Low body mass index is closely related to a high risk of Alzheimer’s disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia’s association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = − 0.206, p = 0.020) and clinical outcomes (low MMSE, β = − 1.364, p = 0.025; low SVLT, β = − 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications.

Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy

PurposeThe purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN).MethodsPatients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis.Results133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803).ConclusionCofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.