Multi-omics Technologies Research Articles

In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies

In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies

Current biological implications and clinical relevance of metastatic circulating tumor cells.

Metastatic disease and cancer recurrence are the primary causes of cancer-related deaths. Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) are the driving forces behind the spread of cancer cells. The emergence and development of liquid biopsy using rare CTCs as a minimally invasive strategy for early-stage tumor detection and improved tumor management is a promising advancement in recent years. However, before blood sample analysis and clinical translation, precise isolation of CTCs from patients' blood based on their biophysical properties, followed by molecular identification of CTCs using single-cell multi-omics technologies is necessary to understand tumor heterogeneity and provide effective diagnosis and monitoring of cancer progression. Additionally, understanding the origin, morphological variation, and interaction between CTCs and the primary and metastatic tumor niche, as well as and regulatory immune cells, will offer new insights into the development of CTC-based advanced tumor targeting in the future clinical trials.

Drought-tolerant wheat for enhancing global food security.

Wheat is among the most produced grain crops of the world and alone provides a fifth of the world's calories and protein. Wheat has played a key role in food security since the crop served as a Neolithic founder crop for the establishment of world agriculture. Projections showing a decline in global wheat yields in changing climates imply that food security targets could be jeopardized. Increased frequency and intensity of drought occurrence is evident in major wheat-producing regions worldwide, and notably, the wheat-producing area under drought is projected to swell globally by 60% by the end of the 21st century. Wheat yields are significantly reduced due to changes in plant morphological, physiological, biochemical, and molecular activities in response to drought stress. Advances in wheat genetics, multi-omics technologies and plant phenotyping have enhanced the understanding of crop responses to drought conditions. Research has elucidated key genomic regions, candidate genes, signalling molecules and associated networks that orchestrate tolerance mechanisms under drought stress. Robust and low-cost selection tools are now available in wheat for screening genetic variations for drought tolerance traits. New breeding techniques and selection tools open a unique opportunity to tailor future wheat crop with optimal trait combinations that help withstand extreme drought. Adoption of the new wheat varieties will increase crop diversity in rain-fed agriculture and ensure sustainable improvements in crop yields to safeguard the world's food security in drier environments.

Abstract 4120919: Cell physiology and multi-omics analysis revealed disordered embryogenesis as early as mesoderm specification in models of Holt-Oram Syndrome

Introduction: Congenital heart diseases (CHDs) are the leading cause of childhood morbidity and mortality. The dysregulation of several cardiac transcription factors (TFs) leads to CHD. The coordination of several cardiac TFs is required and essential for cardiogenesis. However, the mechanisms to acquire its cardiac cell identity remain unclear. Hypothesis: Mutant Tbx5 dysregulates embryogenesis during mesoderm specification, prior to its expression in the tissues in Holt-Oram syndrome. Methods: Using cellular physiology and multiomics analysis in both human ES cells and a zebrafish model of TBX5 germline mutation. we evaluated embryonic structure and function, prior to the onset of gastrulation in the context of both heterozygous and homozygous TBX5 mutation. Results: Zebrafish time course transcriptome profiles over gastrulation revealed that loss of Tbx5 impacted transcriptional profiles at the blastula stage. Single cell RNA sequencing (scRNA-seq) on 16243 zebrafish blastula stage cells showed loss of Tbx5 impacted transcription noise at the blastula stage prior to the expression of zygotic Tbx5 with associated effects on chromatin accessibility using omni-assay for transposase-accessible chromatin (ATAC) and evidence of aberrant Wnt signaling even at the blastula stage. Embryo-wide cell structure and function were abnormal in both Tbx5 mutant zebrafish heterozygotes or homozygotes. To validate Undifferentiated human ES cell H3K4me3 Cleavage Under Targets&Release Using Nuclease (CUT&RUN) also showed abnormal Wnt signaling in TBX5 homozygous mutation and TBX5 CUT&RUN showed aberrant mesoderm pathway. Calcium imaging analysis demonstrated the lowest excitation frequency in TBX5 homozygous mutation prior to mesoderm specification. TBX5 homozygous human ES derived mesoderm cells exhibited low expression levels of mesoderm marker genes compared to TBX5 wild type mesoderm. Conclusion: Integrating single cell physiology and multi-omics technologies, we idneifified fundamental dysregulation of embryogenesis in mutant cardiac-restricted gene disorder prior to mesoderm specification or the zygotic expression of the mutant gene. These findings suggest that Tbx5 started to determine cell fate prior to mesoderm specification by altering chromatin accessibilities and histone modification. Tbx5 affected mesoderm differentiation by influencing Wnt signaling and cell physiology.

PATH-66. MOLECULAR FEATURES RELATED TO LONG-TERM SURVIVAL IN GLIOBLASTOMA

Abstract Glioblastoma Multiforme (GBM) remains the most common malignant primary brain tumor in adults, with a dismal prognosis that rarely exceeds beyond 2 years of survival despite multimodal treatment. While small fractions of GBM patients seem to display extended survival, the underlying mechanisms for this peculiarity remain largely unknown. Previously published investigations of long-term survivors (LTS) usually incorporate small numbers of patients, non-uniform definition of LTS and rarely provide a comprehensive molecular analysis. With advances in multi-omics technologies and their integration with disease diagnostics, numerous prognostic molecular markers have been proposed. So far, only O6-methylguanine-DNA-methyltransferase (MGMT) gene promotor hypermethylation was linked to outcome and therapy response. We aim to investigate omics characteristics associated with LTS. Molecularly confirmed Isocitrate Dehydrogenase (IDH) wildtype GBM patients, >18 years old, operated and treated at our institution between 2013 and 2020 and living ≥5 years post-diagnosis (LTS = 62) or 1-2 years (STS = 62) were identified. Clinical and demographic characteristics were matched. Tumor tissues was analyzed with targeted next generation sequencing (NGS) and compared between LTS and STS. In addition, methylation analysis was done for all LTS. Results will be presented. We hope to shed a broader light on the molecular drivers behind the LTS in GBM patients, that will provide prognostic markers and potential targets for novel treatments.

TMET-24. MULTI-OMIC CHARACTERIZATION OF THE TEMPORAL METABOLIC ADAPTATIONS UNDERPINNING THERAPY RESISTANCE AND TUMOR RECURRENCE IN GLIOBLASTOMA

Abstract Therapy resistance and tumor recurrence are barriers to achieving long-term survival in cancer patients, particularly evident in glioblastoma (GBM), known for its dismal 5-year survival rate below 10%. Despite aggressive treatment regimens, including maximal resection, alkylating chemotherapy, and radiation, the majority of GBM patients experience relapse within 7-9 months post-initial intervention. Recurrent GBM poses surgical challenges and resists subsequent treatments, leading to an almost universally fatal outcome and an average survival of 12-18 months. Metabolic networks can serve as ancient stress-protection mechanisms that operate independently of genomic changes, offering an initial line of defense against exogenous pressures. Although the role of metabolism in cancer has gained prominence, our understanding of the metabolic adaptations following chemoradiotherapy and their contributions to therapy resistance and tumor recurrence in highly aggressive GBM tumors remains incomplete. We postulate that metabolic adaptations play a pivotal role in facilitating therapy resistance and GBM recurrence. Exploring the metabolic dependencies of these persistent cells may unveil vulnerabilities for therapeutic exploitation to counteract chemoradiotherapy resistance. We established clinically relevant patient-derived in vitro and in vivo models mirroring the standard GBM treatment protocol. Using state-of-the-art single-cell and bulk multi-omics technologies, we profiled the temporal transcriptomic and metabolomic adaptations from therapy-naïve primary GBM to chemoradiotherapy-resistant recurrent tumors. Our findings revealed unique metabolic transitions that occurred during chemoradiotherapy treatment in GBM cells that were conserved in vitro and in vivo across ten genetically diverse GBM patients. In a pre-clinical animal trial, a novel metabolism-targeting combinatorial treatment regimen prevented the emergence of recurrent tumors and significantly prolonged survival compared to chemoradiotherapy alone. Altogether, our results uncover distinct metabolic adaptations mediating therapy resistance and tumor recurrence in GBM. These findings emphasize the need to consider metabolic flexibility and dependencies for effective therapeutic strategies, offering potential avenues to overcome chemoresistance in recurrent GBM tumors.

Anticancer Drug Development, Pharmaceutical Progress

Anticancer drug development is becoming complex and demanding because human cancer leads to 12% of global human mortality. Chemical and pharmacological breakthroughs play leading roles in updating drug evaluation and development for different types of tumors. Chemical and pharmacological breakthroughs manifest in different facets. A large proportion of financial and workload increases in drug discovery must be paid off. In front of complexity, difficulties, and financial increase of drug development, evaluative promotion must go miniature- wise and single-cell-wise. Multi-omics knowledge and technology are greatly expanded and understood in depth. This type of technical trend is suitable for current experimental exploration and clinical occasions. Technical and pharmacologic advances are especially emphasized to address this trend. Presently, the anticancer pharmaceutical study is multi-faceted and risk-taking. To keep up this momentum, multi-disciplinary drug evaluation, clinical selection, and combination principles should be discovered. Past and futuristic chemical and pharmacological interactions and breakthroughs are discussed. In summary, the landscape of pharmaceutical investigation should be integrated with chemical and pharmacological knowledge in every facet of drug development and clinical personalization.

Integration of CRISPR/Cas9 with multi-omics technologies to engineer secondary metabolite productions in medicinal plant: Challenges and Prospects.

Plants acts asliving chemical factories that may create a large variety of secondary metabolites, most of which are used in pharmaceutical products. The production of these secondary metabolites is often much lower. Moreover, the primary constraint after discovering potential metabolites is the capacity to manufacture sufficiently for use in industrial and therapeutic contexts. The development of omics technology has brought revolutionary discoveries in various scientific fields, including transcriptomics, metabolomics, and genome sequencing. The metabolic pathways leading to the utilization of new secondary metabolites in the pharmaceutical industry can be identified with the use of these technologies. Genome editing (GEd) is a versatile technology primarily used for site-directed DNA insertions, deletions, replacements, base editing, and activation/repression at the targeted locus. Utilizing GEd techniques such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR-associated protein 9), metabolic pathways engineered to synthesize bioactive metabolites optimally. This article will briefly discuss omics and CRISPR/Cas9-based methods to improve secondary metabolite production in medicinal plants.

Multimodal AI/ML for discovering novel biomarkers and predicting disease using multi-omics profiles of patients with cardiovascular diseases

Cardiovascular diseases (CVDs) are complex, multifactorial conditions that require personalized assessment and treatment. Advancements in multi-omics technologies, namely RNA sequencing and whole-genome sequencing, have provided translational researchers with a comprehensive view of the human genome. The efficient synthesis and analysis of this data through integrated approach that characterizes genetic variants alongside expression patterns linked to emerging phenotypes, can reveal novel biomarkers and enable the segmentation of patient populations based on personalized risk factors. In this study, we present a cutting-edge methodology rooted in the integration of traditional bioinformatics, classical statistics, and multimodal machine learning techniques. Our approach has the potential to uncover the intricate mechanisms underlying CVD, enabling patient-specific risk and response profiling. We sourced transcriptomic expression data and single nucleotide polymorphisms (SNPs) from both CVD patients and healthy controls. By integrating these multi-omics datasets with clinical demographic information, we generated patient-specific profiles. Utilizing a robust feature selection approach, we identified a signature of 27 transcriptomic features and SNPs that are effective predictors of CVD. Differential expression analysis, combined with minimum redundancy maximum relevance feature selection, highlighted biomarkers that explain the disease phenotype. This approach prioritizes both biological relevance and efficiency in machine learning. We employed Combination Annotation Dependent Depletion scores and allele frequencies to identify variants with pathogenic characteristics in CVD patients. Classification models trained on this signature demonstrated high-accuracy predictions for CVD. The best performing of these models was an XGBoost classifier optimized via Bayesian hyperparameter tuning, which was able to correctly classify all patients in our test dataset. Using SHapley Additive exPlanations, we created risk assessments for patients, offering further contextualization of these predictions in a clinical setting. Across the cohort, RPL36AP37 and HBA1 were scored as the most important biomarkers for predicting CVDs. A comprehensive literature review revealed that a substantial portion of the diagnostic biomarkers identified have previously been associated with CVD. The framework we propose in this study is unbiased and generalizable to other diseases and disorders.

Environmental endocrine disrupting chemical-DEHP exposure-provoked biotoxicity about microbiota-gut-mammary axis in lactating mice via multi-omics technologies

Plastics, pervasive in humans and nature, often contain Di (2-ethylhexyl) phthalate (DEHP) that enhance plastic’s elasticity. However, DEHP is an environmental endocrine disruptor, affecting organisms upon exposure. Understanding mammary gland development in lactating females is crucial for offspring nourishment and dairy production. Employing multi-omics technology, this study aimed to uncover DEHP’s impact on the microbial–gut–mammary axis. Forty mice were exposed to varying DEHP doses for 18 d. We performed 16S sequencing, metabolomics, mammary tissue observation, and gene expression profiling. Results revealed DEHP’s influence on microbial diversity, with increased Lactobacillus abundance and reduced Proteobacteria, alongside colonic inflammation. Elevated GMP and adenosine 5′-monophosphate levels in the bloodstream were noted, while ascorbic acid, glycitein, and others decreased. MEHP, a DEHP metabolite, damaged mammary tissues, inhibiting ERK1/2 phosphorylation, triggering apoptosis and ferroptosis. These findings unveil potential therapeutic targets for DEHP-induced chronic toxicity in humans and animals, aiding dairy livestock health and human well-being. This study underscores the importance of understanding the adverse effects of DEHP exposure on mammalian systems.

The frontier of precision medicine: application of single-cell multi-omics in preimplantation genetic diagnosis.

The advent of single-cell multi-omics technologies has revolutionized the landscape of preimplantation genetic diagnosis (PGD), offering unprecedented insights into the genetic, transcriptomic, and proteomic profiles of individual cells in early-stage embryos. This breakthrough holds the promise of enhancing the accuracy, efficiency, and scope of PGD, thereby significantly improving outcomes in assisted reproductive technologies (ARTs) and genetic disease prevention. This review provides a comprehensive overview of the importance of PGD in the context of precision medicine and elucidates how single-cell multi-omics technologies have transformed this field. We begin with a brief history of PGD, highlighting its evolution and application in detecting genetic disorders and facilitating ART. Subsequently, we delve into the principles, methodologies, and applications of single-cell genomics, transcriptomics, and proteomics in PGD, emphasizing their role in improving diagnostic precision and efficiency. Furthermore, we review significant recent advances within this domain, including key experimental designs, findings, and their implications for PGD practices. The advantages and limitations of these studies are analyzed to assess their potential impact on the future development of PGD technologies. Looking forward, we discuss the emerging research directions and challenges, focusing on technological advancements, new application areas, and strategies to overcome existing limitations. In conclusion, this review underscores the pivotal role of single-cell multi-omics in PGD, highlighting its potential to drive the progress of precision medicine and personalized treatment strategies, thereby marking a new era in reproductive genetics and healthcare.

Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly.

Delineation of structural variants (SVs) at sequence resolution in highly repetitive genomic regions has long been intractable. The sequence properties, origins, and functional effects of classes of genomic rearrangements such as ring chromosomes and Robertsonian translocations thus remain unknown. To resolve these complex structures, we leveraged several recent milestones in the field, including (1) the emergence of long-read sequencing, (2) the gapless telomere-to-telomere (T2T) assembly, and (3) a tool (BigClipper) to discover chromosomal rearrangements from long reads. We applied these technologies across 13 cases with ring chromosomes, Robertsonian translocations, and complex SVs that were unresolved by short reads, followed by validation using optical genome mapping (OGM). Our analyses resolved 10 of 13 cases, including a Robertsonian translocation and all ring chromosomes. Multiple breakpoints were localized to genomic regions previously recalcitrant to sequencing such as acrocentric p-arms, ribosomal DNA arrays, and telomeric repeats, and involved complex structures such as a deletion-inversion and interchromosomal dispersed duplications. We further performed methylation profiling from long-read data to discover phased differential methylation in a gene promoter proximal to a ring fusion, suggesting a long-range position effect (LRPE) with heterochromatin spreading. Breakpoint sequences suggested mechanisms of SV formation such as microhomology-mediated and non-homologous end-joining, as well as non-allelic homologous recombination. These methods provide some of the first glimpses into the sequence resolution of Robertsonian translocations and illuminate the structural diversity of ring chromosomes and complex chromosomal rearrangements with implications for genome biology, prediction of LRPEs from integrated multi-omics technologies, and molecular diagnostics in rare disease cases.

A review on protein utilization and its interactions with carbohydrate and lipid from a molecular perspective in aquaculture: An implication beyond growth.

The world's increasing need for protein faces challenges in aquaculture production. New applications and tools will need to be added at every stage of the manufacturing line to attain this expansion sustainably, safely, and effectively. Utilizing experimental methods to increase aquatic animal production has become more common as aquatic biotechnology has advanced. High-throughput omics technologies have been introduced to address these issues, including transcriptomic, metabolomic, proteomic, and genomes. But it also faces many difficulties, like other food manufacturing industries. One of the best and most durable approaches to address these issues is probably to understand nutritional requirements and modify diet based on need. Molecular approaches are a subset of multiomics technology. Previously, most of the published work was devoted to the biochemical aspects of protein-lipid interactions in biological systems. In this review, we explore this idea and highlight various works that fall under the umbrella of nutrigenomics, with a particular emphasis on protein utilization and its interactions with carbohydrates and lipids.

GRANULOSA CELL DYSFUNCTION AND IMPAIRED OOCYTE MATURATION PLAY SIGNIFICANT ROLES IN POLYCYSTIC OVARY SYNDROME PATHOGENESIS

The polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of reproductive age worldwide. It is characterized by hyperandrogenism, ovarian dysfunction, and polycystic ovarian morphology.With a particular focus on granulosa cell dysfunction and abnormal oocyte maturation, this comprehensive review explores the intricate molecular mechanisms driving PCOS pathogenesis. PCOS is characterized by hormonal and metabolic disturbances caused by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and the insulin-like growth factor 1 (IGF1) signaling pathway.In this review, we discuss the dysregulation of certain lncRNAs, such as NEAT1, and miRNAs, including miR-29a-3p, in PCOS granulosa cells, as well as how these dysregulations affect cell proliferation, insulin sensitivity, and steroidogenesis. This study examines the interaction between non-coding RNAs and the IGF1 system, which reveals an intricate regulatory network involved in follicular development and ovarian function. These pathways are altered in expression and activity, which has implications for how oocytes mature and how fertility is affected.In addition, this review emphasizes the interconnected nature of granulosa cell dysfunction, oocyte maturation defects, and systemic metabolic disturbances in PCOS pathogenesis. Granulosa cells have the potential to be used as a research and therapeutic intervention focus, due to their accessibility and central role in ovarian function.Additionally, we propose future research directions using advanced technologies such as single cell sequencing and multi-omics technologies. According to the review, studies that focus on granulosa cells can help develop novel diagnostic markers, personalized treatment strategies, and potential PCOS-based therapies.In addition to providing insight into the molecular underpinnings of PCOS, this study sets the stage for future investigations aimed at improving diagnosis, management, and treatment.

Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.

Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown. This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated. The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

Multi-omics approaches for abiotic stress tolerance in rice (Oryza sativa L.)

Rice, one of the world's staple crops, faces significant challenges due to abiotic stresses such as drought, salinity and extreme temperatures, which threaten global food security. Traditional breeding methods have limitations in developing stress-tolerant rice varieties within a short time frame. Thus, there is a growing interest in employing multi-omics approaches, integrating genomics, transcriptomics, proteomics, metabolomics and epigenomics, to unravel the complex molecular mechanisms underlying abiotic stress tolerance in rice. In contrast to a single-omics method, this combination of multi-dimensional approaches provides an extensive understanding of cellular dynamics under abiotic stress conditions. This review discusses recent advances in multi-omics technologies and their applications in dissecting the molecular responses of rice to abiotic stresses. It highlights the integration of multi-omics data to identify critical genes, pathways and regulatory networks involved in stress responses and tolerance mechanisms.Furthermore, it explores the potential of multi-omics-assisted breeding strategies for developing stress-tolerant rice varieties with improved agronomic traits. The challenges and future perspectives in utilizing multi-omics approaches to enhance rice's abiotic stress tolerance are also discussed. Overall, multi-omics approaches offer a comprehensive platform to understand the molecular basis of stress tolerance in rice and accelerate the development of resilient varieties to ensure global food security.

Ouabain Ameliorates Alzheimer’s Disease-Associated Neuropathology and Cognitive Impairment in FAD4T Mice

Background: Alzheimer’s disease (AD) is a common clinical neurodegenerative disorder, primarily characterized by progressive cognitive decline and behavioral abnormalities. The hallmark pathological changes of AD include widespread neuronal degeneration, plaques formed by the deposition of amyloid β-protein (Aβ), and neurofibrillary tangles (NFTs). With the acceleration of global aging, the incidence of AD is rising year by year, making it a major global public health concern. Due to the complex pathology of AD, finding effective interventions has become a key focus of research. Ouabain (OUA), a cardiac glycoside, is well-known for its efficacy in treating heart disease. Recent studies have also indicated its potential in AD therapy, although its exact mechanism of action remains unclear. Methods: This study integrates bioinformatics, multi-omics technologies, and in vivo and in vitro experiments to investigate the effects of OUA on the pathophysiological changes of AD and its underlying molecular mechanisms. Results: This study analyzed the expression of the triggering receptor expressed on myeloid cells 2 (TREM2) across different stages of AD using bioinformatics. Serum samples from patients were used to validate soluble TREM2 (sTREM2) levels. Using an Aβ1-42-induced microglial cell model, we confirmed that OUA enhances the PI3K/AKT signaling pathway activation by upregulating TREM2, which reduces neuroinflammation and promotes the transition of microglia from an M1 proinflammatory state to an M2 anti-inflammatory state. To evaluate the in vivo effects of OUA, we assessed the learning and memory capacity of FAD4T transgenic mice using the Morris water maze and contextual fear conditioning tests. We used real-time quantitative PCR, immunohistochemistry, and Western blotting to measure the expression of inflammation-associated cytokines and to assess microglia polarization. OUA enhances cognitive function in FAD4T mice and has been confirmed to modulate microglial M1/M2 phenotypes both in vitro and in vivo. Furthermore, through bioinformatics analysis, molecular docking, and experimental validation, TREM2 was identified as a potential target for OUA. It regulates PI3K/Akt signaling pathway activation, playing a crucial role in OUA-mediated M2 microglial polarization and its anti-inflammatory effects in models involving Aβ1-42-stimulated BV-2 cells and FAD4T mice. Conclusions: These findings indicate that OUA exerts anti-neuroinflammatory effects by regulating microglial polarization, reducing the production of inflammatory mediators, and activating the PI3K/Akt signaling pathway. Given its natural origin and dual effects on microglial polarization and neuroinflammation, OUA emerges as a promising therapeutic candidate for neuroinflammatory diseases such as AD.

Explore the mechanism of yishenjiangya formula in the treatment of senile hypertension based on multi-omics technology

Ethnopharmacological relevanceThe Yishenjiangya formula (YSJ) is a traditional Chinese medicine (TCM) primarily composed of qi-tonifying components. This classic formula is commonly utilized to treat kidney qi deficiency in elderly patients with hypertension. According to TCM, maintaining a balance between qi and blood is crucial for stable blood pressure. Kidney qi deficiency can disrupt this balance, altering fluid shear force and, ultimately, leading to hypertension, particularly in elderly populations. Despite YSJ's efficacy in treating hypertension, its specific anti-hypertensive mechanisms remain unclear. Aim of the studyYSJ is commonly prescribed for elderly patients with hypertension. Earlier metabolomics studies demonstrated that YSJ exerts antihypertensive effects by influencing four key pathways: linoleic acid metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. This study aims to combine metabolomic and proteomic analyses to thoroughly understand the molecular biological mechanisms responsible for YSJ's anti-hypertensive properties. MethodsUltra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) metabolomics, combined with Label-Free Quantitation (LFQ) proteomics, was employed to analyze serum samples from elderly individuals with and without hypertension pre- and post-YSJ intervention. Serum levels of candidate proteins were assessed using enzyme-linked immunosorbent assay, and receiver operating characteristic curves were used to evaluate the diagnostic performance of the target proteins. ResultsEight differentially expressed metabolites and three differentially expressed proteins were identified as potential therapeutic targets of YSJ. These substances are primarily involved in unsaturated fatty acid metabolism, fluid shear stress and atherosclerosis pathway, primary bile acid biosynthesis, proline metabolism, apoptosis, and endoplasmic reticulum stress. YSJ exerts its therapeutic effects on hypertension in the elderly by modulating these pathways. ConclusionsYSJ effectively treats senile hypertension. By analyzing the correlation between therapeutic targets and pathways, YSJ's anti-hypertensive effect was achieved by inhibiting lipid peroxidation and matrix degeneration. Combining metabolomics and proteomics provides an effective method for uncovering YSJ's anti-hypertensive mechanisms.

Investigation of the polysaccharides synthesis enhancement mechanism from Agaricus bitoquis (Quél.) Sacc Chaidam and its fermentation regulation technology system based on multi-omics technologies

The polysaccharides (PS) of Agaricus bitoquis (Quél.) Sacc. Chaidam (ABSC) had attracted the attention of researchers due to their strong anti hypoxia, antioxidant, and anti fatigue activities. Therefore, this article focuses on studying the regulatory channels of exogenous additives-Lycium ruthenicum Murr. Anthocyanin (LRA) to delay fungus cell aging and promote the incremental synthesis of PS from ABSC, and optimizing the regulation system for pilot fermentation experiments. The joint analysis of Ultra High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (UHPLC-Q-TOFMS) and RNA sequencing (RNA-seq) database elucidates that at the molecular level, the crude extract of LRA inhibits the Telecommunications Association (TCA) cycle, transferring carbon metabolism to the synthesis of polysaccharide precursors (UDP-glucose, UDP-galactose, etc.), promoting the synthesis of PS, promoting the formation of key antioxidant substances (including flavonoids such as quercetin and alginate), improving cell membrane fluidity (saturated fatty acid to unsaturated conversion) and enhancing the degradation of toxic substances (oxidized glutathione), thereby promoting the anti-aging activity and PS synthesis ability of mycelial cells; LRA-adding could enhance the activity in the pilot fermentation of ABSC, which make the mycelia biomass, EPS and IPS production were significantly increased (89.04 %, 65.46 % and 37.64 % respectively) compared with the untreatment control. Based on the optimal fermentation system of PS synthesized in mycelium by adding LRA, Logistic, Gauss, and Asymptotic kinetic equations were used to describe the cell growth, product synthesis and regulatory substrate consumption from ABSC. The correlation coefficients of three models were all above 0.95, indicating a good fit between the experimental values and predicted value, this indicated ABSC fermentation kinetics model could better simulate the actual production process and provide theoretical data for the industrial production of polysaccharides. The results demonstrated that the present proposed LRA intensification approach could be useful to boost up the fermentation of ABSC, which possibly applied to yield increase and fermentation product acquisition of macrofungi.

Gut microbiota, serum metabolites, and lipids related to blood glucose control and type 1 diabetes.

The composition and function of gut microbiota, lipids, and metabolites in patients with type 1 diabetes (T1D) or its association with glycemic control remains unknown. We aimed to use multi-omics sequencing technology and machine learning (ML) approaches to investigate potential function and relationships among the gut microbiota, lipids, and metabolites in T1D patients at varied glycemic levels. We conducted a multi-omics analysis of the gut microbiome from fecal samples, metabolites, and lipids obtained from serum samples, collected from a cohort of 72 T1D patients. The patients were divided into two groups based on their hemoglobin A1c (HbA1c) levels. 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in composition and function of gut microbiota, metabolites, and lipids. The linear discriminant analysis, Shapley additive explanations (SHAP) algorithm, and ML algorithms revealed the enrichment of Bacteroides_nordii, Bacteroides_cellulosilyticus in the glycemic control (GC) group, while Bacteroides_coprocola and Sutterella_wadsworthensis were enriched in the poor glycemic control (PGC) group. Several metabolic enrichment sets like fatty acid biosynthesis and glycerol phosphate shuttle metabolism were different between two groups. Bacteroides_nordii exhibited a negative association with D-fructose, a component involved in the starch and sucrose metabolism pathway, as well as with monoglycerides (16:0) involved in the glycerolipid metabolism pathway. We identified distinct characteristics of gut microbiota, metabolites, and lipids in T1D patients exhibiting different levels of glycemic control. Through comprehensive analysis, microbiota (Bacteroides_nordii, Bacteroides_coprocola), metabolites (D-fructose), and lipids (Monoglycerides) may serve as potential mediators that communicated the interaction between the gut, circulatory systems, and glucose fluctuations in T1D patients.