PubMed

J Pharm Anal. 2024 Apr;14(4):100910. doi: 10.1016/j.jpha.2023.11.017. Epub 2023 Nov 29.ABSTRACTEclipta prostrata L. has been used in traditional medicine and known for its liver-protective properties for centuries. Wedelolactone (WEL) and demethylwedelolactone (DWEL) are the major coumarins found in E. prostrata L. However, the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease (NAFLD) still remains to be explored. Utilizing a well-established zebrafish model of thioacetamide (TAA)-induced liver injury, the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis. Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver. The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped, and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized. Based on spatial metabolomics and transcriptomics, we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL. Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD, and presents a "multi-omics" platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.PMID:38655398 | PMC:PMC11035064 | DOI:10.1016/j.jpha.2023.11.017

Heliyon. 2024 Apr 15;10(8):e29598. doi: 10.1016/j.heliyon.2024.e29598. eCollection 2024 Apr 30.ABSTRACTBACKGROUND: Intestinal bacteria significantly contribute to the metabolism of intestinal epithelial tissues. As the occurrence and development of radiation enteritis (RE) depend on the "co-metabolism" microenvironment formed by the host and intestinal microbiota, which involves complex influencing factors and strong correlations, ordinary techniques struggle to fully explain the underlying mechanisms. However, given that it is based on systems biology, metabolomics analysis is well-suited to address these issues. This study aimed to analyze the metabolomic changes in urine, serum, and fecal samples during volumetric modulated arc therapy (VMAT) for cervical cancer and screen for characteristic metabolites of severe acute radiation enteritis (SARE) and RE.METHODS: We enrolled 50 patients who received radiotherapy for cervical cancer. Urine, serum, and fecal samples of patients were collected at one day before radiotherapy and the second week, fourth week, and sixth week after the start of radiotherapy. Control group samples were collected during the baseline period. Differential metabolites were identified by metabolomics analysis; co-metabolic pathways were clarified. We used the mini-SOM library for incorporating characteristic metabolites, and established metabolite classification models for predicting SARE and RE.RESULTS: Urine and serum sample data showed remarkable clustering effect; metabolomics data of the fecal supernatant were evidently disturbed. Patient sample analyses during VMAT revealed the following. Urine samples: Downregulation of the pyrimidine and riboflavin metabolism pathways as well as initial upregulation followed by downregulation of arginine and proline metabolism pathways and the arginine biosynthesis pathway. Fecal samples: Upregulation of linoleic acid and phenylalanine metabolic pathways and initial downregulation followed by upregulation of arachidonic acid (AA) metabolic pathways. Serum samples: Initial upregulation followed by downregulation of the arginine biosynthesis pathway and downregulation of glutathione, AA, and arginine and proline metabolic pathways.CONCLUSION: Patients with cervical cancer exhibited characteristic metabolic pathways and characteristic metabolites predicting RE and SARE were screened out. An effective RE mini-SOM classification model was successfully established.PMID:38655340 | PMC:PMC11036041 | DOI:10.1016/j.heliyon.2024.e29598

iScience. 2024 Apr 9;27(5):109698. doi: 10.1016/j.isci.2024.109698. eCollection 2024 May 17.ABSTRACTMounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of wild-type (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn-/-) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP's involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn-/- primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.PMID:38655198 | PMC:PMC11035374 | DOI:10.1016/j.isci.2024.109698

Physiol Plant. 2024 Mar-Apr;176(2):e14314. doi: 10.1111/ppl.14314.ABSTRACTThe ancient bayberry demonstrates superior resistance to both biotic and abiotic stresses compared to cultivated bayberry, yet the underlying mechanisms remain largely unexplored. This study investigates whether long-term bayberry cultivation enhances stress resistance through modulation of tissue-specific microbes and metabolites. Employing microbiome amplicon sequencing alongside untargeted mass spectrometry analysis, we scrutinize the role of endosphere and rhizosphere microbial communities and metabolites in shaping the differential resistance observed between ancient and cultivated bayberry trees. Our findings highlight the presence of core microbiome and metabolites across various bayberry tissues, suggesting that the heightened resistance of ancient bayberry may stem from alterations in rhizosphere and endosphere microbial communities and secondary metabolites. Specifically, enrichment of Bacillus in roots and stems, Pseudomonas in leaves, and Mortierella in rhizosphere soil of ancient bayberry was noted. Furthermore, correlation analysis underscores the significance of enriched microbial species in enhancing ancient bayberry's resistance to stresses, with elevated levels of resistance-associated metabolites such as beta-myrcene, benzothiazole, L-glutamic acid, and gamma-aminobutyric acid identified through GC-MS metabolomics analysis. The beneficial role of these resistance-associated metabolites was further elucidated through assessment of their promotive and allelopathic effects, as well as their phytostatic and antioxidant functions in lettuce plants. Ultimately, our study delves into the intrinsic reasons behind the greater resistance of ancient bayberry to biotic and abiotic stresses by evaluating the impact of long-term planting on the microbial community and metabolites in the bayberry endosphere and rhizosphere, shedding light on the complex dynamics of host-microbial interactions.PMID:38654401 | DOI:10.1111/ppl.14314

BMC Microbiol. 2024 Apr 23;24(1):134. doi: 10.1186/s12866-024-03276-7.ABSTRACTBACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent.METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed.RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28.CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.PMID:38654189 | DOI:10.1186/s12866-024-03276-7

Cell Death Dis. 2024 Apr 23;15(4):286. doi: 10.1038/s41419-024-06681-y.ABSTRACTThe progression of human degenerative and hypoxic/ischemic diseases is accompanied by widespread cell death. One death process linking iron-catalyzed reactive species with lipid peroxidation is ferroptosis, which shows hallmarks of both programmed and necrotic death in vitro. While evidence of ferroptosis in neurodegenerative disease is indicated by iron accumulation and involvement of lipids, a stable marker for ferroptosis has not been identified. Its prevalence is thus undetermined in human pathophysiology, impeding recognition of disease areas and clinical investigations with candidate drugs. Here, we identified ferroptosis marker antigens by analyzing surface protein dynamics and discovered a single protein, Fatty Acid-Binding Protein 5 (FABP5), which was stabilized at the cell surface and specifically elevated in ferroptotic cell death. Ectopic expression and lipidomics assays demonstrated that FABP5 drives redistribution of redox-sensitive lipids and ferroptosis sensitivity in a positive-feedback loop, indicating a role as a functional biomarker. Notably, immunodetection of FABP5 in mouse stroke penumbra and in hypoxic postmortem patients was distinctly associated with hypoxically damaged neurons. Retrospective cell death characterized here by the novel ferroptosis biomarker FABP5 thus provides first evidence for a long-hypothesized intrinsic ferroptosis in hypoxia and inaugurates a means for pathological detection of ferroptosis in tissue.PMID:38653992 | DOI:10.1038/s41419-024-06681-y

Nat Commun. 2024 Apr 23;15(1):3422. doi: 10.1038/s41467-024-47771-x.ABSTRACTTargeting Anaplastic lymphoma kinase (ALK) is a promising therapeutic strategy for aberrant ALK-expressing malignancies including neuroblastoma, but resistance to ALK tyrosine kinase inhibitors (ALK TKI) is a distinct possibility necessitating drug combination therapeutic approaches. Using high-throughput, genome-wide CRISPR-Cas9 knockout screens, we identify miR-1304-5p loss as a desensitizer to ALK TKIs in aberrant ALK-expressing neuroblastoma; inhibition of miR-1304-5p decreases, while mimics of this miRNA increase the sensitivity of neuroblastoma cells to ALK TKIs. We show that miR-1304-5p targets NRAS, decreasing cell viability via induction of apoptosis. It follows that the farnesyltransferase inhibitor (FTI) lonafarnib in addition to ALK TKIs act synergistically in neuroblastoma, inducing apoptosis in vitro. In particular, on combined treatment of neuroblastoma patient derived xenografts with an FTI and an ALK TKI complete regression of tumour growth is observed although tumours rapidly regrow on cessation of therapy. Overall, our data suggests that combined use of ALK TKIs and FTIs, constitutes a therapeutic approach to treat high risk neuroblastoma although prolonged therapy is likely required to prevent relapse.PMID:38653965 | DOI:10.1038/s41467-024-47771-x

Inflammation. 2024 Apr 24. doi: 10.1007/s10753-024-02032-3. Online ahead of print.ABSTRACTAging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.PMID:38653921 | DOI:10.1007/s10753-024-02032-3

Food Chem. 2024 Apr 16;450:139375. doi: 10.1016/j.foodchem.2024.139375. Online ahead of print.ABSTRACTCooked off-flavor was produced during the processing of concentrated peach puree (CPP), which led to aroma deterioration. Enzymatic treatment was beneficial in eliminating off-flavors and improving the aroma quality. Herein, the efficacy of glycosidase (AR2000), glucose oxidation (GOD), and their combination on the inhibition of off-flavors and aroma enhancement were evaluated. Compared with CPP, contents of benzaldehyde, benzyl alcohol, nonanal, and linalool increased by 198%, 1222%, 781%, and 71% after AR2000 treatment via the metabolisms of shikimate, glucose, linoleic acid, and linolenic acid, leading to the strengthening of floral and grassy. Due to the removal of 1-octen-3-one via linolenic acid metabolism, cooked off-flavor could be significantly weakened by GOD. Furthermore, Furthermore, the combination of AR2000 and GOD could not only inhibit the production of 1-octen-3-one to weaken the cooked note but also enhance grassy and floral attributes via the increase of aldehydes and alcohols.PMID:38653052 | DOI:10.1016/j.foodchem.2024.139375

Food Chem. 2024 Apr 17;450:139379. doi: 10.1016/j.foodchem.2024.139379. Online ahead of print.ABSTRACTRaspberries are known to contain valuable metabolites and possess a robust antioxidant capacity. However, the impact of different tablet processing stages on the nutritional content and flavor profile of raspberries remains unclear. The dynamic profile of functional and volatile metabolites was investigated through foodomics combined with UPLC-MS/MS-based widely targeted metabolomics and HS-SPME-GC-MS, and antioxidant capacities were assessed during tablet processing. 1336 functional metabolites and 645 volatile metabolites were identified. Results indicated tablets retained 34% ∼ 61% of the total volatile contents. In addition, the conversion intensity of functional metabolites was consistent with the order of "Tableting > Freeze-drying > Crushing". Compared to raspberry, tablets showed higher antioxidant activity, which was positively correlated with vitamin contents. This study elucidated that tablet formation demonstrated advantages in antioxidation and aroma retention, which may provide insights for enhancing quality during the tableting process.PMID:38653050 | DOI:10.1016/j.foodchem.2024.139379

Environ Sci Technol. 2024 Apr 23. doi: 10.1021/acs.est.3c10904. Online ahead of print.ABSTRACTPermeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.PMID:38652822 | DOI:10.1021/acs.est.3c10904

J Agric Food Chem. 2024 Apr 23. doi: 10.1021/acs.jafc.4c00346. Online ahead of print.ABSTRACTTriterpenoids from Camellia species comprise a diverse class of bioactive compounds with great therapeutic potential. However, triterpene biosynthesis in tea plants (Camellia sinensis) remains elusive. Here, we identified eight putative 2,3-oxidosqualene cyclase (OSC) genes (CsOSC1-8) from the tea genome and characterized the functions of five through heterologous expression in yeast and tobacco and transient overexpression in tea plants. CsOSC1 was found to be a β-amyrin synthase, whereas CsOSC4, 5, and 6 exhibited multifunctional α-amyrin synthase activity. Molecular docking and site-directed mutagenesis showed that the CsOSC6M259T/W260L double mutant yielded >40% lupeol, while the CsOSC1 W259L single mutant alone was sufficient for lupeol production. The V732F mutation in CsOSC5 altered product formation from friedelin to taraxasterol and ψ-taraxasterol. The L254 M mutation in the cycloartenol synthase CsOSC8 enhanced the catalytic activity. Our findings shed light on the molecular basis governing triterpene diversity in tea plants and offer potential avenues for OSC engineering.PMID:38652774 | DOI:10.1021/acs.jafc.4c00346

J Clin Invest. 2024 Apr 23:e167371. doi: 10.1172/JCI167371. Online ahead of print.ABSTRACTCarbohydrates and lipids provide the majority of substrates to fuel mitochondrial oxidative phosphorylation (OXPHOS). Metabolic inflexibility, defined as an impaired ability to switch between these fuels, is implicated in a number of metabolic diseases. Here we explore the mechanism by which physical inactivity promotes metabolic inflexibility in skeletal muscle. We developed a mouse model of sedentariness, small mouse cage (SMC) that, unlike other classic models of disuse in mice, faithfully recapitulated metabolic responses that occur in humans. Bioenergetic phenotyping of skeletal muscle mitochondria displayed metabolic inflexibility induced by physical inactivity, demonstrated by a reduction in pyruvate-stimulated respiration (JO2) in absence of a change in palmitate-stimulated JO2. Pyruvate resistance in these mitochondria was likely driven by a decrease in phosphatidylethanolamine (PE) abundance in the mitochondrial membrane. Reduction in mitochondrial PE by heterozygous deletion of phosphatidylserine decarboxylase (PSD) was sufficient to induce metabolic inflexibility measured at the whole-body level, as well as at the level of skeletal muscle mitochondria. Low mitochondrial PE in C2C12 myotubes was sufficient to increase glucose flux towards lactate. We further implicate that resistance to pyruvate metabolism is due to attenuated mitochondrial entry via mitochondrial pyruvate carrier (MPC). These findings suggest a mechanism by which mitochondrial PE directly regulates MPC activity to modulate metabolic flexibility in mice.PMID:38652544 | DOI:10.1172/JCI167371

J Clin Sleep Med. 2024 Apr 23. doi: 10.5664/jcsm.11160. Online ahead of print.ABSTRACTSTUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) poses a significant health hazard, as intermittent hypoxia inflicts damage throughout the body and is considered a critical risk factor for metabolic disorders. The aim of this study was to establish a metabolic profile for patients with OSAHS using nontargeted metabolomics detection techniques, providing a basis for OSAHS diagnosis and novel biological marker identification.METHODS: Forty-five patients with OSAHS composed the OSAHS group, and 44 healthy volunteers composed the control group. Nontargeted metabolomics technology was used to analyze participants' urinary metabolites. Differentially abundant metabolites were screened and correlated through hierarchical clustering analysis. We constructed a composite metabolite diagnostic model using a random forest model. Simultaneously, we analyzed the relationships between 20 metabolites involved in model construction and OSAHS severity.RESULTS: The urinary metabolomics pattern of the OSAHS group exhibited significant changes, demonstrating noticeable differences in metabolic products. Urinary metabolite analysis revealed differences between the mild-moderate OSAHS and severe OSAHS groups. The composite metabolite model constructed in this study demonstrated excellent diagnostic performance not only in distinguishing healthy control participants from patients with mild-moderate OSAHS (AUC = 0.78) and patients with severe OSAHS (AUC = 0.78), but also in discriminating between patients with mild-moderate and severe OSAHS (AUC = 0.71).CONCLUSIONS: This study comprehensively analyzed the urinary metabolomic characteristics of patients with OSAHS. The established composite metabolite model provides robust support for OSAHS diagnosis and severity assessment. Twenty metabolites associated with OSAHS disease severity offer a new perspective for diagnosis.PMID:38652501 | DOI:10.5664/jcsm.11160

Dig Dis Sci. 2024 Apr 23. doi: 10.1007/s10620-024-08446-1. Online ahead of print.ABSTRACTBACKGROUND: Molecular changes in HCC development are largely unknown. As the liver plays a fundamental role in the body's metabolism, metabolic changes are to be expected.AIMS: We aimed to identify metabolomic changes in HCC in comparison to liver cirrhosis (LC) patients, which could potentially serve as novel biomarkers for HCC diagnosis and prognosis.METHODS: Metabolite expression from 38 HCC from the SORAMIC trial and 32 LC patients were analyzed by mass spectrometry. Metabolites with significant differences between LC and HCC at baseline were analyzed regarding expression over follow-up. In addition, association with overall survival was tested using univariate Cox proportional-hazard analysis.RESULTS: 41 metabolites showed differential expression between LC and HCC patients. 14 metabolites demonstrated significant changes in HCC patients during follow-up. Campesterol, lysophosphatidylcholine, octadecenoic and octadecadienoic acid, and furoylglycine showed a differential expression in the local ablation vs. palliative care group. High expression of eight metabolites (octadecenoic acid, 2-hydroxybutyrate, myo-inositol, isocitrate, erythronic acid, creatinine, pseudouridine, and erythrol) were associated with poor overall survival. The association between poor OS and octadecenoic acid and creatinine remained statistically significant even after adjusting for tumor burden and LC severity.CONCLUSION: Our findings give promising insides into the metabolic changes during HCC carcinogenesis and provide candidate biomarkers for future studies. Campesterol and furoylglycine in particular were identified as possible biomarkers for HCC progression. Moreover, eight metabolites were detected as predictors for poor overall survival.PMID:38652389 | DOI:10.1007/s10620-024-08446-1

Breast Cancer. 2024 Apr 23. doi: 10.1007/s12282-024-01579-1. Online ahead of print.ABSTRACTBACKGROUND: Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis.METHODS: We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model.RESULTS: In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18-0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (Pinteraction = 0.006) as well as PR (Pinteraction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant.CONCLUSION: Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.PMID:38652345 | DOI:10.1007/s12282-024-01579-1

Future Microbiol. 2024 Apr 23. doi: 10.2217/fmb-2024-0043. Online ahead of print.ABSTRACTAim: Proof-of-concept study, highlighting the clinical diagnostic ability of FT-IR compared with MALDI-TOF MS, combined with WGS. Materials & methods: 104 pathogenic isolates of Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus were analyzed. Results: Overall prediction accuracy was 99.6% in FT-IR and 95.8% in MALDI-TOF-MS. Analysis of N. meningitidis serogroups was superior in FT-IR compared with MALDI-TOF-MS. Phylogenetic relationship of S. pyogenes was similar by FT-IR and WGS, but not S. aureus or S. pneumoniae. Clinical severity was associated with the zinc ABC transporter and DNA repair genes in S. pneumoniae and cell wall proteins (biofilm formation, antibiotic and complement permeability) in S. aureus via WGS. Conclusion: FT-IR warrants further clinical evaluation as a promising diagnostic tool.PMID:38652264 | DOI:10.2217/fmb-2024-0043

Curr Microbiol. 2024 Apr 23;81(6):154. doi: 10.1007/s00284-024-03653-5.ABSTRACTHelicobacter pylori, a member of the clade campylobacteria, is the leading cause of chronic gastritis and gastric cancer. Virulence and antibiotic resistance of H. pylori are of great concern to public health. However, the relationship between virulence and antibiotic resistance genes in H. pylori in relation to other campylobacteria remains unclear. Using the virulence and comprehensive antibiotic resistance databases, we explored all available 354 complete genomes of H. pylori and compared it with 90 species of campylobacteria for virulence and antibiotic resistance genes/proteins. On average, H. pylori had 129 virulence genes, highest among Helicobacter spp. and 71 antibiotic resistance genes, one of the lowest among campylobacteria. Just 2.6% of virulence genes were shared by all campylobacterial members, whereas 9.4% were unique to H. pylori. The cytotoxin-associated genes (cags) seemed to be exclusive to H. pylori. Majority of the isolates from Asia and South America were cag2-negative and many antibiotic resistance genes showed isolate-specific patterns of occurrence. Just 15 (8.8%) antibiotic resistance genes, but 103 (66%) virulence genes including 25 cags were proteomically identified in H. pylori. Arcobacterial members showed large variation in the number of antibiotic resistance genes and there was a positive relation with the genome size. Large repository of antibiotic resistance genes in campylobacteria and a unique set of virulence genes might have important implications in shaping the course of virulence and antibiotic resistance in H. pylori.PMID:38652129 | DOI:10.1007/s00284-024-03653-5

Microbiol Resour Announc. 2024 Apr 23:e0003324. doi: 10.1128/mra.00033-24. Online ahead of print.ABSTRACTRivers are critical ecosystems that impact global biogeochemical cycles. Nonetheless, a mechanistic understanding of river microbial metabolisms and their influences on geochemistry is lacking. Here, we announce metaproteomes of river sediments that are paired with metagenomes and metabolites, enabling an understanding of the microbial underpinnings of river respiration.PMID:38651910 | DOI:10.1128/mra.00033-24

Int J Cancer. 2024 Apr 23. doi: 10.1002/ijc.34929. Online ahead of print.ABSTRACTThe etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.PMID:38651675 | DOI:10.1002/ijc.34929