PubMed

Food Res Int. 2024 May;183:114190. doi: 10.1016/j.foodres.2024.114190. Epub 2024 Mar 3.ABSTRACTThis study aimed to determine the effect of different frozen temperatures during storage on the quality of Antarctic krill (Euphausia superba) and assess the change at the metabolite level via a combination of physicochemical property analysis, liquid chromatography-tandem mass spectrometry (LC-MS) based non-targeted metabolomics profiling. Regarding samples stored at -20 °C, the expressions of 7055 metabolites were elevated, while 2313 were downregulated. Lipids and lipid molecules had the highest proportion of differential metabolites. A total of 432 discriminatory metabolites with Kyoto Encyclopedia of Genes and Genomes (KEGG) IDs was obtained. We also observed that the concentrations of differential bitter free amino acids (FAAs) and oxidation products of arachidonic and linoleic acid increased. Moreover, as the storage temperature increased, the freshness, umami, and sweetness components were considerably reduced. Furthermore, results indicated that the color, pH and water-holding capacity (WHC) were potential indicators of quality deterioration, while inosinic acid was a probable biomarker for umami degradation of frozen Antarctic krill. In conclusion, this study demonstrates that storage at lower temperatures can be beneficial for maintaining the freshness of Antarctic krill from macro and micro perspectives.PMID:38760127 | DOI:10.1016/j.foodres.2024.114190

Gastroenterology. 2024 May 15:S0016-5085(24)04917-5. doi: 10.1053/j.gastro.2024.05.005. Online ahead of print.ABSTRACTGastrointestinal (GI) cancers are the leading cause of new cancer cases and cancer-related deaths worldwide. The treatment strategies for patients with GI tumors have focused on oncogenic molecular profiles associated with tumor cells. Recent evidence demonstrated that tumor cell functions are modulated by its microenvironment, compromising fibroblasts, ECMs, microbiome, immune cells, and the enteric nervous system. Along with the TME components, alterations in key metabolic pathways have emerged as a hallmark of tumor cells. From these perspectives, this review will highlight the functions of different cellular components of the GI tumor microenvironment (TME) and their implications for treatment. Furthermore, we discuss the major metabolic reprogramming in GI tumor cells and how understanding metabolic rewiring could lead to new therapeutic strategies. Finally, we briefly summarize the targeted agents currently being studied in GI cancers. Understanding the complex interplay between tumor cell-intrinsic and cell-extrinsic during tumor progression is critical for developing new therapeutic strategies.PMID:38759843 | DOI:10.1053/j.gastro.2024.05.005

Adv Drug Deliv Rev. 2024 May 15:115332. doi: 10.1016/j.addr.2024.115332. Online ahead of print.ABSTRACTRecent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.PMID:38759702 | DOI:10.1016/j.addr.2024.115332

Food Chem. 2024 May 6;452:139565. doi: 10.1016/j.foodchem.2024.139565. Online ahead of print.ABSTRACTMicrogreens constitute natural-based foods with health-promoting properties mediated by the accumulation of glucosinolates (GLs) and phenolic compounds (PCs), although their bioaccessibility may limit their nutritional potential. This work subjected eight Brassicaceae microgreens to in vitro gastrointestinal digestion and large intestine fermentation before the metabolomics profiling of PCs and GLs. The application of multivariate statistics effectively discriminated among species and their interaction with in vitro digestion phases. The flavonoids associated with arugula and the aliphatic GLs related to red cabbage and cauliflower were identified as discriminant markers among microgreen species. The multi-omics integration along in vitro digestion and fermentation predicted bioaccessible markers, featuring potential candidates that may eventually be responsible for these functional foods' nutritional properties. This combined analytical and computational framework provided a promising platform to predict the nutritional metabolome-wide outcome of functional food consumption, as in the case of microgreens.PMID:38759437 | DOI:10.1016/j.foodchem.2024.139565

Food Chem. 2024 May 10;452:139616. doi: 10.1016/j.foodchem.2024.139616. Online ahead of print.ABSTRACTTo investigate the effects of inoculating with three strains of lactic acid bacteria on prune wine quality during malolactic fermentation, this study determined its antioxidant activity, phenolic compounds, organic acids, and volatile/non-volatile metabolites. The results showed that inoculation with Lactobacillus paracasei SMN-LBK improved the antioxidant activity and phenolic compounds of prune wine. 73 VOCs were detected in prune wine by HS-SPME-GC-MS, and VOC content increased by 4.3% and 9.1% in MLFS and MLFB, respectively. Lactobacillus delbrueckii subsp. Bulgaricus showed better potential for winemaking, and citral and 5-nonanol, were detected in the MLF samples. 39 shared differential metabolites were screened and their metabolic pathways were investigated based on nontargeted metabolomics. Differences in amino acid and flavonoid content between strains reflected their specificity in flavonoid biosynthesis and amino acid biosynthesis. These findings will provide useful information for the biochemical study and processing of prune wine.PMID:38759436 | DOI:10.1016/j.foodchem.2024.139616

J Pharm Biomed Anal. 2024 May 13;246:116219. doi: 10.1016/j.jpba.2024.116219. Online ahead of print.ABSTRACTQingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1β, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.PMID:38759325 | DOI:10.1016/j.jpba.2024.116219

J Pharm Biomed Anal. 2024 May 14;246:116211. doi: 10.1016/j.jpba.2024.116211. Online ahead of print.ABSTRACTOsteoporosis (OP) is a metabolic bone disease that can lead to major health challenges. The theory of Traditional Chinese medicine believes that kidney-Yin deficiency (KYD) is the main cause of postmenopausal osteoporosis. This study was aimed to investigate the effect of EZW on anti-osteoporosis with KYD, and explore potential mechanisms from the perspective of the kidney, bone and bone marrow through analysis of metabolomics and proteomics. The model of OP with KYD was established by rats treated with bilateral ovariectomy (OVX), and then given intragastric administration of thyroid and reserpine to induce. Micro-CT was applied to determine the microstructures of bone. Serum levels associated with bone turnover markers and kidney-Yin deficiency were detected by enzyme-linked immunosorbent (ELISA) assay. The differential metabolites in the kidney, bone and bone marrow were analyzed by metabolomics. The differentially expressed proteins in these three tissues were detected via proteomics. The findings suggested that EZW could alleviate a variety of metabolites and proteins among the kidney, bone and bone marrow, primarily in amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and lipid metabolism, thus leading to improvements of OP with KYD, which provided theoretical basis for clinical treatment of EZW on OP with KYD.PMID:38759323 | DOI:10.1016/j.jpba.2024.116211

Phytomedicine. 2024 May 3;130:155710. doi: 10.1016/j.phymed.2024.155710. Online ahead of print.ABSTRACTBACKGROUND: Sepsis, a life-threatening condition resulting from uncontrolled host responses to infection, poses a global health challenge with limited therapeutic options. Due to high heterogeneity, sepsis lacks specific therapeutic drugs. Additionally, there remains a significant gap in the clinical management of sepsis regarding personalized and precise medicine.PURPOSE: This review critically examines the scientific landscape surrounding natural products in sepsis and sepsis-mediated inflammation, highlighting their clinical potential.METHODS: Following the PRISMA guidelines, we retrieved articles from PubMed to explore potential natural products with therapeutic effects in sepsis-mediated inflammation.RESULTS: 434 relevant in vitro and in vivo studies were identified and screened. Ultimately, 55 studies were obtained as the supporting resources for the present review. We divided the 55 natural products into three categories: those influencing the synthesis of inflammatory factors, those affecting surface receptors and modulatory factors, and those influencing signaling pathways and the inflammatory cascade.CONCLUSION: Natural products' potential as game-changers in sepsis-mediated inflammation management lies in their ability to modulate hallmarks in sepsis, including inflammation, immunity, and coagulopathy, which provides new therapeutic avenues that are readily accessible and capable of undergoing rapid clinical validation and deployment, offering a gift from nature to humanity. Innovative techniques like bioinformatics, metabolomics, and systems biology offer promising solutions to overcome these obstacles and facilitate the development of natural product-based therapeutics, holding promise for personalized and precise sepsis management and improving patient outcomes. However, standardization, bioavailability, and safety challenges arise during experimental validation and clinical trials of natural products.PMID:38759311 | DOI:10.1016/j.phymed.2024.155710

J Neuroinflammation. 2024 May 17;21(1):132. doi: 10.1186/s12974-024-03121-8.ABSTRACTBACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI).METHODS: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes.RESULTS: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression.CONCLUSION: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.PMID:38760862 | DOI:10.1186/s12974-024-03121-8

J Ovarian Res. 2024 May 17;17(1):105. doi: 10.1186/s13048-024-01411-6.ABSTRACTBACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis.METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL.RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR.CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.PMID:38760835 | DOI:10.1186/s13048-024-01411-6

Mol Cancer. 2024 May 18;23(1):106. doi: 10.1186/s12943-024-02020-z.ABSTRACTAging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time, irrespective of the precise causes, can be confronted with the idea that aging and cancer share common mechanistic grounds that are referred to as 'hallmarks'. Indeed, several hallmarks of aging also contribute to carcinogenesis and tumor progression, but some of the molecular and cellular characteristics of aging may also reduce the probability of developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied by a reduced incidence of neoplastic diseases. We will also discuss the possibility that the aging process itself causes cancer, meaning that the time-dependent degradation of cellular and supracellular functions that accompanies aging produces cancer as a byproduct or 'age-associated disease'. Conversely, cancer and its treatment may erode health and drive the aging process, as this has dramatically been documented for cancer survivors diagnosed during childhood, adolescence, and young adulthood. We conclude that aging and cancer are connected by common superior causes including endogenous and lifestyle factors, as well as by a bidirectional crosstalk, that together render old age not only a risk factor of cancer but also an important parameter that must be considered for therapeutic decisions.PMID:38760832 | DOI:10.1186/s12943-024-02020-z

J Nanobiotechnology. 2024 May 17;22(1):262. doi: 10.1186/s12951-024-02537-x.ABSTRACTBACKGROUND: Nanoplastics, are emerging pollutants, present a potential hazard to food security and human health. Titanium dioxide nanoparticles (Nano-TiO2), serving as nano-fertilizer in agriculture, may be important in alleviating polystyrene nanoplastics (PSNPs) toxicity.RESULTS: Here, we performed transcriptomic, metabolomic and physiological analyzes to identify the role of Nano-TiO2 in regulating the metabolic processes in PSNPs-stressed maize seedlings (Zea mays L.). The growth inhibition by PSNPs stress was partially relieved by Nano-TiO2. Furthermore, when considering the outcomes obtained from RNA-seq, enzyme activity, and metabolite content analyses, it becomes evident that Nano-TiO2 significantly enhance carbon and nitrogen metabolism levels in plants. In comparison to plants that were not subjected to Nano-TiO2, plants exposed to Nano-TiO2 exhibited enhanced capabilities in maintaining higher rates of photosynthesis, sucrose synthesis, nitrogen assimilation, and protein synthesis under stressful conditions. Meanwhile, Nano-TiO2 alleviated the oxidative damage by modulating the antioxidant systems. Interestingly, we also found that Nano-TiO2 significantly enhanced the endogenous melatonin levels in maize seedlings. P-chlorophenylalanine (p-CPA, a melatonin synthesis inhibitor) declined Nano-TiO2-induced PSNPs tolerance.CONCLUSIONS: Taken together, our data show that melatonin is involved in Nano-TiO2-induced growth promotion in maize through the regulation of carbon and nitrogen metabolism.PMID:38760823 | DOI:10.1186/s12951-024-02537-x

BMC Vet Res. 2024 May 17;20(1):208. doi: 10.1186/s12917-024-04057-0.ABSTRACTBACKGROUND: The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown.RESULTS: Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An-Tn. It is worth mentioning that the expression of vitamin D3 and 3,3',5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle.CONCLUSIONS: The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.PMID:38760765 | DOI:10.1186/s12917-024-04057-0

BMC Plant Biol. 2024 May 17;24(1):409. doi: 10.1186/s12870-024-05134-0.ABSTRACTBACKGROUND: Bletilla striata (Thunb.) Reichb. f. (B. striata) is a perennial herbaceous plant in the Orchidaceae family known for its diverse pharmacological activities, such as promoting wound healing, hemostasis, anti-inflammatory effects, antioxidant properties, and immune regulation. Nevertheless, the microbe-plant-metabolite regulation patterns for B. striata remain largely undetermined, especially in the field of rhizosphere microbes. To elucidate the interrelationships between soil physics and chemistry and rhizosphere microbes and metabolites, a comprehensive approach combining metagenome analysis and targeted metabolomics was employed to investigate the rhizosphere soil and tubers from four provinces and eight production areas in China.RESULTS: Our study reveals that the core rhizosphere microbiome of B. striata is predominantly comprised of Paraburkholderia, Methylibium, Bradyrhizobium, Chitinophaga, and Mycobacterium. These microbial species are recognized as potentially beneficial for plants health. Comprehensive analysis revealed a significant association between the accumulation of metabolites, such as militarine and polysaccharides in B. striata and the composition of rhizosphere microbes at the genus level. Furthermore, we found that the soil environment indirectly influenced the metabolite profile of B. striata by affecting the composition of rhizosphere microbes. Notably, our research identifies soil organic carbon as a primary driving factor influencing metabolite accumulation in B. striata.CONCLUSION: Our fndings contribute to an enhanced understanding of the comprehensive regulatory mechanism involving microbe-plant-metabolite interactions. This research provides a theoretical basis for the cultivation of high-quality traditional Chinese medicine B. striata.PMID:38760736 | DOI:10.1186/s12870-024-05134-0

Nat Med. 2024 May 17. doi: 10.1038/s41591-024-02972-1. Online ahead of print.ABSTRACTIn a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.PMID:38760586 | DOI:10.1038/s41591-024-02972-1

J Perinatol. 2024 May 17. doi: 10.1038/s41372-024-01988-2. Online ahead of print.ABSTRACTOBJECTIVE: Preterm infants need enrichment of human milk (HM) for optimal growth. This study evaluated a novel, point-of-care human milk concentration (HMC) process for water removal from fresh HM samples by passive osmotic concentration.STUDY DESIGN: Nineteen fresh HM samples were concentrated by incubation with the HMC devices for 3 h at 4 °C. Pre- and post-concentration HM samples were compared by HM properties for: pH, osmolality, macronutrients, enzyme activity, bioactive, and total cell viability.RESULTS: Passive osmotic concentration reduced HM volume by an average of 16.3% ± 3.8% without a significant effect on pH or cell viability. Ten of the 41 HM components did not differ significantly (p > 0.05) between pre- and post-concentration samples. Twenty-three increased within the expected range by volume reduction. Six increased more than expected, two less than expected, and none decreased significantly.CONCLUSION: Passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within neonatal feeding parameters.PMID:38760580 | DOI:10.1038/s41372-024-01988-2

Nat Commun. 2024 May 17;15(1):4195. doi: 10.1038/s41467-024-48433-8.ABSTRACTOsimertinib (Osi) is a widely used epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). However, the emergence of resistance is inevitable, partly due to the gradual evolution of adaptive resistant cells during initial treatment. Here, we find that Osi treatment rapidly triggers adaptive resistance in tumor cells. Metabolomics analysis reveals a significant enhancement of oxidative phosphorylation (OXPHOS) in Osi adaptive-resistant cells. Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA4-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.PMID:38760351 | DOI:10.1038/s41467-024-48433-8

PLoS One. 2024 May 17;19(5):e0300883. doi: 10.1371/journal.pone.0300883. eCollection 2024.ABSTRACTDevelopment of novel biodosimetry assays and medical countermeasures is needed to obtain a level of radiation preparedness in the event of malicious or accidental mass exposures to ionizing radiation (IR). For biodosimetry, metabolic profiling with mass spectrometry (MS) platforms has identified several small molecules in easily accessible biofluids that are promising for dose reconstruction. As our microbiome has profound effects on biofluid metabolite composition, it is of interest how variation in the host microbiome may affect metabolomics based biodosimetry. Here, we 'knocked out' the microbiome of male and female C57BL/6 mice (Abx mice) using antibiotics and then irradiated (0, 3, or 8 Gy) them to determine the role of the host microbiome on biofluid radiation signatures (1 and 3 d urine, 3 d serum). Biofluid metabolite levels were compared to a sham and irradiated group of mice with a normal microbiome (Abx-con mice). To compare post-irradiation effects in urine, we calculated the Spearman's correlation coefficients of metabolite levels with radiation dose. For selected metabolites of interest, we performed more detailed analyses using linear mixed effect models to determine the effects of radiation dose, time, and microbiome depletion. Serum metabolite levels were compared using an ANOVA. Several metabolites were affected after antibiotic administration in the tryptophan and amino acid pathways, sterol hormone, xenobiotic and bile acid pathways (urine) and lipid metabolism (serum), with a post-irradiation attenuative effect observed for Abx mice. In urine, dose×time interactions were supported for a defined radiation metabolite panel (carnitine, hexosamine-valine-isoleucine [Hex-V-I], creatine, citric acid, and Nε,Nε,Nε-trimethyllysine [TML]) and dose for N1-acetylspermidine, which also provided excellent (AUROC ≥ 0.90) to good (AUROC ≥ 0.80) sensitivity and specificity according to the area under the receiver operator characteristic curve (AUROC) analysis. In serum, a panel consisting of carnitine, citric acid, lysophosphatidylcholine (LysoPC) (14:0), LysoPC (20:3), and LysoPC (22:5) also gave excellent to good sensitivity and specificity for identifying post-irradiated individuals at 3 d. Although the microbiome affected the basal levels and/or post-irradiation levels of these metabolites, their utility in dose reconstruction irrespective of microbiome status is encouraging for the use of metabolomics as a novel biodosimetry assay.PMID:38758927 | DOI:10.1371/journal.pone.0300883

J Comput Biol. 2024 May 17. doi: 10.1089/cmb.2024.0520. Online ahead of print.ABSTRACTInformation on the structure of molecules, retrieved via biochemical databases, plays a pivotal role in various disciplines, including metabolomics, systems biology, and drug discovery. No such database can be complete and it is often necessary to incorporate data from several sources. However, the molecular structure for a given compound is not necessarily consistent between databases. This article presents StructRecon, a novel tool for resolving unique molecular structures from database identifiers. Currently, identifiers from BiGG, ChEBI, Escherichia coli Metabolome Database (ECMDB), MetaNetX, and PubChem are supported. StructRecon traverses the cross-links between entries in different databases to construct what we call identifier graphs. The goal of these graphs is to offer a more complete view of the total information available on a given compound across all the supported databases. To reconcile discrepancies met during the traversal of the databases, we develop an extensible model for molecular structure supporting multiple independent levels of detail, which allows standardization of the structure to be applied iteratively. In some cases, our standardization approach results in multiple candidate structures for a given compound, in which case a random walk-based algorithm is used to select the most likely structure among incompatible alternatives. As a case study, we applied StructRecon to the EColiCore2 model. We found at least one structure for 98.66% of its compounds, which is more than twice as many as possible when using the databases in more standard ways not considering the complex network of cross-database references captured by our identifier graphs. StructRecon is open-source and modular, which enables support for more databases in the future.PMID:38758924 | DOI:10.1089/cmb.2024.0520

PLoS One. 2024 May 17;19(5):e0299780. doi: 10.1371/journal.pone.0299780. eCollection 2024.ABSTRACTMicroalgae's ability to mitigate flue gas is an attractive technology that can valorize gas components through biomass conversion. However, tolerance and growth must be ideal; therefore, acclimation strategies are suggested. Here, we compared the transcriptome and lipidome of Desmodesmus abundans strains acclimated to high CO2 (HCA) and low CO2 (LCA) under continuous supply of model flue gas (MFG) and incomplete culture medium (BG11-N-S). Initial growth and nitrogen consumption from MFG were superior in strain HCA, reaching maximum productivity a day before strain LCA. However, similar productivities were attained at the end of the run, probably because maximum photobioreactor capacity was reached. RNA-seq analysis during exponential growth resulted in 16,435 up-regulated and 4,219 down-regulated contigs in strain HCA compared to LCA. Most differentially expressed genes (DEGs) were related to nucleotides, amino acids, C fixation, central carbon metabolism, and proton pumps. In all pathways, a higher number of up-regulated contigs with a greater magnitude of change were observed in strain HCA. Also, cellular component GO terms of chloroplast and photosystems, N transporters, and secondary metabolic pathways of interest, such as starch and triacylglycerols (TG), exhibited this pattern. RT-qPCR confirmed N transporters expression. Lipidome analysis showed increased glycerophospholipids in strain HCA, while LCA exhibited glycerolipids. Cell structure and biomass composition also revealed strains differences. HCA possessed a thicker cell wall and presented a higher content of pigments, while LCA accumulated starch and lipids, validating transcriptome and lipidome data. Overall, results showed significant differences between strains, where characteristic features of adaptation and tolerance to high CO2 might be related to the capacity to maintain a higher flux of internal C, regulate intracellular acidification, active N transporters, and synthesis of essential macromolecules for photosynthetic growth.PMID:38758755 | DOI:10.1371/journal.pone.0299780