PubMed

Front Mol Biosci. 2023 Mar 10;10:1168941. doi: 10.3389/fmolb.2023.1168941. eCollection 2023.NO ABSTRACTPMID:36968280 | PMC:PMC10037091 | DOI:10.3389/fmolb.2023.1168941

Front Mol Biosci. 2023 Mar 10;10:1165720. doi: 10.3389/fmolb.2023.1165720. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fmolb.2022.1070394.].PMID:36968275 | PMC:PMC10036897 | DOI:10.3389/fmolb.2023.1165720

Front Cell Dev Biol. 2023 Mar 8;11:1129009. doi: 10.3389/fcell.2023.1129009. eCollection 2023.ABSTRACTATP wasting is recognized as an efficient strategy to enhance metabolic activity and productivity of specific metabolites in several microorganisms. However, such strategy has been rarely implemented in Streptomyces species whereas antibiotic production by members of this genus is known to be triggered in condition of phosphate limitation that is correlated with a low ATP content. In consequence, to assess the effects of ATP spilling on the primary and specialized metabolisms of Streptomyces, the gene encoding the small synthetic protein DX, that has high affinity for ATP and dephosphorylates ATP into ADP, was cloned in the integrative vector pOSV10 under the control of the strong ErmE promoter. This construct and the empty vector were introduced into the species Streptomyces albogriseolus/viridodiastaticus yielding A37 and A36, respectively. A37 yielded higher biomass than A36 indicating that the DX-mediated ATP degradation resulted into a stimulation of A37 metabolism, consistently with what was reported in other microorganisms. The comparative analysis of the metabolomes of A36 and A37 revealed that A37 had a lower content in glycolytic and Tricarboxylic Acid Cycle intermediates as well as in amino acids than A36, these metabolites being consumed for biomass generation in A37. In contrast, the abundance of other molecules indicative either of energetic stress (ADP, AMP, UMP, ornithine and thymine), of activation (NAD and threonic acid) or inhibition (citramalic acid, fatty acids, TAG and L-alanine) of the oxidative metabolism, was higher in A37 than in A36. Furthermore, hydroxyl-pyrimidine derivatives and polycyclic aromatic polyketide antibiotics belonging to the angucycline class and thought to have a negative impact on respiration were also more abundantly produced by A37 than by A36. This comparative analysis thus revealed the occurrence in A37 of antagonistic metabolic strategies, namely, activation or slowing down of oxidative metabolism and respiration, to maintain the cellular energetic balance. This study thus demonstrated that DX constitutes an efficient biotechnological tool to enhance the expression of the specialized metabolic pathways present in the Streptomyces genomes that may include cryptic pathways. Its use thus might lead to the discovery of novel bioactive molecules potentially useful to human health.PMID:36968208 | PMC:PMC10030506 | DOI:10.3389/fcell.2023.1129009

iScience. 2023 Mar 7;26(4):106346. doi: 10.1016/j.isci.2023.106346. eCollection 2023 Apr 21.ABSTRACTPeriodontitis may aggravate the development of nonalcoholic fatty liver disease (NAFLD); however, the precise mechanism is unknown. In this study, salivary microbiota collected from patients with periodontitis was transferred intragastrically to obese mice induced by high-fat diet. Microbiomics and metabolomics analysis were performed to assess the influence of periodontitis salivary microbiota on gut microbiome and liver metabolism. Periodontitis salivary microbiota altered gut microbiota composition and exacerbated intestinal barrier dysfunction in obese mice. Subsequently, the bacterial lipopolysaccharide transported to liver may activate the toll-like receptor 4 signaling and cause the release of pro-inflammatory factors. Moreover, the tryptophan-kynurenine-AhR signal axis was upregulated in liver, which may be related to aggravated hepatic steatosis and glucolipid metabolism dysregulation during NAFLD development. This study indicated that in the context of obesity, periodontitis salivary microbiota may aggravate the pathological progression of NAFLD, in which the tryptophan-AhR pathway may play a key role.PMID:36968080 | PMC:PMC10031158 | DOI:10.1016/j.isci.2023.106346

iScience. 2023 Mar 3;26(4):106329. doi: 10.1016/j.isci.2023.106329. eCollection 2023 Apr 21.ABSTRACTRespiratory syncytial virus (RSV) is an important pathogen causing pneumonia in children. Few studies have used multi-omics data to investigate the pathogenies of RSV pneumonia. Here, metabolomics was first used to identify potential biomarkers for RSV diagnosis. In the training cohort, serum from 36 healthy controls (HCs), 45 RSV pneumonia children, and 32 infectious disease controls (IDCs) were recruited. After analyses, six metabolites had potential diagnostic value. Using an independent cohort of 49 subjects, two biomarkers (neuromedin N and histidyl-proline diketopiperazine) were validated. Next, multi-omics analysis were applied to analyze the pathogenies of RSV pneumonia. Accumulation of collagen in the serum of RSVs indicated that RSV infection could lead to increased levels of soluble collage. Activation of the complement system and imbalance in lipid metabolism were also observed in RSV patients. The multi-omics analysis presented here revealed the signature protein and metabolite changes in serum caused by RSV infection.PMID:36968072 | PMC:PMC10034469 | DOI:10.1016/j.isci.2023.106329

iScience. 2023 Mar 5;26(4):106328. doi: 10.1016/j.isci.2023.106328. eCollection 2023 Apr 21.ABSTRACTHypobaric hypoxia (HH) is the primary challenge at highland. Prolonged HH exposure impairs right cardiac function. Mitochondria-associated membrane (MAM) plays a principal role in regulating mitochondrial function under hypoxia, but the mechanism was unclear. In this study, proteomics analysis identified that PACS2, a key protein in MAM, and mitophagy were downregulated in HH. Metabolomics analysis indicated suppression of glucose and fatty acids aerobic oxidation in HH conditions. Cardiomyocyte Pacs2 deficiency disrupted MAM formation and endoplasmic reticulum (ER)-mitochondria calcium flux, further inhibiting mitophagy and energy metabolism in HH. Pacs2 overexpression reversed these effects. Cardiac-specific knockout of Pacs2 exacerbated mitophagy inhibition, cardiomyocyte injury, and right cardiac dysfunction induced by HH. Conditional knock-in of Pacs2 recovered HH-induced right cardiac impairment. Thus, PACS2 is essential for protecting cardiomyocytes through ER-mitochondria calcium flux, mitophagy, and mitochondrial energy metabolism. Our work provides insight into the mechanism of HH-induced cardiomyocyte injury and potential targets for maintaining the right cardiac function at the highland.PMID:36968068 | PMC:PMC10034453 | DOI:10.1016/j.isci.2023.106328

PeerJ. 2023 Mar 20;11:e14539. doi: 10.7717/peerj.14539. eCollection 2023.ABSTRACTPURPOSE: Plant secondary metabolites are used to treat various human diseases. However, it is difficult to produce a large number of specific metabolites, which largely limits their medicinal applications. Many methods, such as drought and nutrient application, have been used to induce the biosynthetic production of secondary metabolites. Among these secondary metabolite-inducing methods, mechanical wounding maintains the composition of secondary metabolites with little potential risk. However, the effects of mechanical stress have not been fully investigated, and thus this method remains widely unused.METHODS: In this study, we used metabolomics to investigate the metabolites produced in the upper and lower leaves of Catharanthus roseus in response to mechanical wounding.RESULTS: In the upper leaves, 13 different secondary metabolites (three terpenoid indole alkaloids and 10 phenolic compounds) were screened using an orthogonal partial least squares discriminant analysis (OPLS-DA) score plot. The mechanical wounding of different plant parts affected the production of secondary metabolites. Specifically, when lower leaves were mechanically wounded, the upper leaves became a strong source of resources. Conversely, when upper leaves were injured, the upper leaves themselves became a resource sink. Changes in the source-sink relationship reflected a new balance between resource tradeoff and the upregulation or downregulation of certain metabolic pathways.CONCLUSION: Our findings suggest that mechanical wounding to specific plant parts is a novel approach to increase the biosynthetic production of specific secondary metabolites. These results indicate the need for a reevaluation of production practices for secondary metabolites from select commercial plants.PMID:36968002 | PMC:PMC10035419 | DOI:10.7717/peerj.14539

Front Endocrinol (Lausanne). 2023 Mar 8;14:1131771. doi: 10.3389/fendo.2023.1131771. eCollection 2023.ABSTRACTTo figure out the differentially changed metabolites and disturbed pathways in follicular fluid (FF) of patients with OHSS in comparison to the control group undergoing in vitro fertilization (IVF), we conducted this metabolomic analysis between two groups, the OHSS group included 30 patients treated with oocyte retrieval and developed OHSS in the next 7-14 days, while another 30 patients without OHSS tendency were selected as the control group. The FF samples were obtained during the process of oocyte retrieval. FF samples were analyzed using ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS). The results identified a total of 59 differentially changed metabolites, including 33 decreased metabolites (P < 0.01) and 26 increased metabolites (P < 0.01) in FF of OHSS compared with the control group. 12 metabolites could be the most valuable biomarkers for OHSS based on ROC results. Our correlation analyses showed that deoxyinosine levels were found positively correlated with serum estradiol (E2) levels in OHSS patients, while L-isoleucine, pyruvic acid, maleamate, and arachidonic acid were found to be positively correlated with the number of retrieved oocytes. Furthermore, 4-hydroxyphenylacetaldehyde, deoxycorticosterone, creatinine, and creatine were found to be negatively associated with serum E2 levels, while 4-hydroxyphenylacetaldehyde, L-carnitine, isovaleric acid and L-2-hydroxyglutaric acid were negatively related with the number of oocytes retrieved in OHSS patients. Taken together, our study provides better identification of OHSS FF metabolic dynamics, suggesting the metabolic compounds can be used as valuable predictors or treatment targets of OHSS.PMID:36967756 | PMC:PMC10031058 | DOI:10.3389/fendo.2023.1131771

J Environ Manage. 2023 Jun 15;336:117602. doi: 10.1016/j.jenvman.2023.117602. Epub 2023 Mar 10.ABSTRACTBiochar has been shown to affect the nitrogen (N) cycle in soil, however, it is unknown how this occurs. Therefore, we used metabolomics, high-throughput sequencing, and quantitative PCR to explore biochar and nitrogen fertilizer effects on the mitigation mechanisms of adverse environments in acidic soil. In the current research, we used acidic soil and maize straw biochar (pyrolyzed at 400 °C with limited oxygen). Three maize straw biochar levels (B1; 0t ha-1, B2; 45 t ha-1, and B3; 90 t ha-1) along with three N fertilizer (urea) levels (N1; 0 kg ha-1, N2; 225 kg ha-1 mg kg-1, and N3; 450 kg ha-1 mg kg-1) were employed in a sixty-day pot experiment. We found that the formation of NH+ 4-N was faster at 0-10 days, while the formation of NO- 3-N occurred at 20-35 days. Furthermore, the combined application of biochar and N fertilizer most effectively boosted soil inorganic N contents compared to biochar and N fertilizer treatments alone. The B3 treatment increased the total N and total inorganic N by 0.2-24.2% and 55.2-91.7%, respectively. Soil microorganism, N fixation, and nitrification capabilities increased with biochar and N fertilizer addition in terms of N-cycling-functional genes. Biochar-N fertilizer had a greater impact on the soil bacterial community and their diversity and richness. Metabolomics revealed 756 distinct metabolites, including 8 substantially upregulated metabolites and 21 significantly downregulated metabolites. A significant amount of lipids and organic acids were formed by biochar-N fertilizer treatments. Thus, biochar and N fertilizer triggered soil metabolism by affecting bacterial community structure, and N-cycling of the soil micro-ecological environment.PMID:36967687 | DOI:10.1016/j.jenvman.2023.117602

Immunol Cell Biol. 2023 Mar 26. doi: 10.1111/imcb.12642. Online ahead of print.ABSTRACTCO2 is produced during aerobic respiration. Normally, levels of CO2 in the blood are tightly regulated but pCO2 can rise (hypercapnia, pCO2 > 45 mmHg) in patients with lung diseases e.g. Chronic Obstructive Pulmonary Disease (COPD). Hypercapnia is a risk factor in COPD but may be of benefit in the context of destructive inflammation. The effects of CO2 per se, on transcription, independent of pH change are poorly understood and warrant further investigation. Here we elucidate the influence of hypercapnia on monocytes and macrophages through integration of state-of-the-art RNA-sequencing, metabolic and metabolomic approaches. THP-1 monocytes and IL4 polarised primary murine macrophages were exposed to 5% CO2 Vs 10% CO2 for up to 24 h in pH- buffered conditions. In hypercapnia, we identified ~370 differentially expressed genes (DEGs) under basal and ~1889 DEGs under LPS-stimulated conditions in monocytes. Transcripts relating to both mitochondrial and nuclear-encoded gene expression were enhanced in hypercapnia in basal and LPS-stimulated cells. Mitochondrial DNA content was not enhanced, but acylcarnitine species and genes associated with fatty acid metabolism were increased in hypercapnia. Primary macrophages exposed to hypercapnia also increased activation of genes associated with fatty acid metabolism and reduced activation of genes associated with glycolysis. Thus, hypercapnia elicits metabolic shifts in lipid metabolism in monocytes and macrophages under pH buffered conditions. These data indicate that CO2 is an important modulator of monocyte transcription that can influence immunometabolic signalling in immune cells in hypercapnia. These immunometabolic insights may be of benefit in the treatment of patients experiencing hypercapnia.PMID:36967673 | DOI:10.1111/imcb.12642

Int Microbiol. 2023 Mar 27. doi: 10.1007/s10123-023-00349-x. Online ahead of print.ABSTRACTSepsis causes high mortality in intensive care units. Although there have been many studies on the gut microbiota in patients with sepsis, the impact of sepsis on the gut microbiota has not been directly determined because the treatment of sepsis also affects the gut microbiota. Therefore, we designed this animal experiment to explore gut microbiota alterations during sepsis. Mice were divided into two groups, mice that survived less than 3 days and mice that survived more than 3 days. Fecal samples collected on the day of cecal ligation and puncture (CLP), as well as on the 3rd and 7th days after CLP, were subjected to microbial community analysis and nontargeted metabolomics analysis. The results showed significantly lower bacterial diversity in fecal samples after CLP. At the genus level, the fecal samples obtained on the 3rd and 7th days after CLP exhibited significantly increased relative abundances of Bacteroides, Helicobacter, etc., and significantly decreased relative abundances of Alloprevotella, Prevotella, etc. Innate metabolite levels were significantly different in mice that survived less than 3 days and mice that survived more than 3 days. In conclusion, CLP-induced sepsis in mice changes the structure of the gut microbiome, and innate metabolites affect the prognosis of septic mice.PMID:36967434 | DOI:10.1007/s10123-023-00349-x

J Nutr. 2022 Apr;152(4):1118-1129. doi: 10.1093/jn/nxac006. Epub 2023 Feb 18.ABSTRACTBACKGROUND: Few studies have assessed the integrative effects of diet, BMI, and exercise on postprandial changes in energy and circulating metabolic profiles.OBJECTIVES: We aimed to assess the collective effects of 3 isocaloric meals high in carbohydrate (74.2% energy), fat (64.6% energy), or protein (39.5% energy) on energy expenditure and clinical and metabolomic biomarkers under resting and exercise conditions in normal-weight and overweight/obese men.METHODS: This crossover controlled acute trial included 20 normal-weight (BMI, 18.5 to <24 kg/m2) and 20 overweight/obese (BMI ≥24 kg/m2) men aged 18-45 years. Each of 3 test meals was provided for 2 continuous days: a resting day without exercise, followed by an exercise day with a bicycling exercise of 50% maximal oxygen consumption (postprandial 90-120 minutes). Energy expenditure (exploratory outcome of primary interest) was measured using indirect calorimetry. Fasting and postprandial 2-hour serum clinical and metabolomic biomarkers (secondary interest) were measured. Mixed models were used to examine the effects of meal, time, and/or BMI category.RESULTS: On the resting day, no significant between-meal differences were detected for energy expenditure. However, high-carbohydrate and high-fat meals induced the highest postprandial 2-hour increase in glucose (0.34 ± 0.15 mmol/L) and triglyceride (0.95 ± 0.09 mmol/L), respectively, while the high-protein meal reduced glucose (-0.48 ± 0.08 mmol/L) and total cholesterol (-0.01 ± 0.03 mmol/L; all Pmeal values < 0.001). On the exercise day, a high-carbohydrate meal significantly promoted the carbohydrate oxidation rate but suppressed the fat oxidation rate (Pmeal < 0.05), while its postprandial glucose response was attenuated by bicycling (-0.31 ± 0.03 mmol/L; Pexercise < 0.001). We identified 69 metabolites as key features in discriminating between the 3 meals, and overweight/obese men had more varieties of metabolites than normal-weight men.CONCLUSIONS: Three isocaloric meals induced unique postprandial changes in clinical and metabolomic biomarkers, while exercise prevented the hyperglycemia induced by a high-carbohydrate meal. Overweight/obese men were more responsive to the meal challenges than normal-weight men. This trial was registered at clinicaltrials.gov as NCT03231618.PMID:36967169 | DOI:10.1093/jn/nxac006

J Nutr. 2022 Apr;152(4):1107-1117. doi: 10.1093/jn/nxac004. Epub 2023 Feb 18.ABSTRACTBACKGROUND: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, whereas protein density associations were mixed.OBJECTIVES: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber.METHODS: Prospective disease association analyses were undertaken in Women's Health Initiative (WHI) cohorts of postmenopausal US women, aged 50-79 y when enrolled at 40 US clinical centers. Biomarkers were developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-y (median) follow-up period, using HR regression methods.RESULTS: Previously reported elevations in cardiovascular disease (CVD) with higher-protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had an HR of 1.20 (95% CI: 1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with a 20% increment HR factor of 0.89 (95% CI: 0.83, 0.94). Cancer risk showed little association with fiber density, whereas diabetes risk had a 20% increment HR of 0.93 (95% CI: 0.88, 0.98) relative to the HRs for total carbohydrate density.CONCLUSIONS: In a population of postmenopausal US women, CVD risk was associated with high-animal-protein and low-fiber diets, cancer risk was associated with low-carbohydrate diets, and diabetes risk was associated with low-fiber/low-carbohydrate diets.PMID:36967168 | DOI:10.1093/jn/nxac004

Neuroscience. 2023 Mar 24:S0306-4522(23)00132-X. doi: 10.1016/j.neuroscience.2023.03.016. Online ahead of print.ABSTRACTThe circadian clock can coordinate, regulate and predict physiology and behavior in response to the standard light-dark (LD: 12h light and 12h dark) cycle. If we alter the LD cycle by exposing mice to constant darkness (DD: 00h light and 24h dark), it can perturb behavior, the brain, and associated physiological parameters. The length of DD exposure and the sex of experimental animals are crucial variables that could alter the impact of DD on the brain, behavior, and physiology, which have not yet been explored. We exposed mice to DD for three and five weeks and studied their impact on 1) behavior, 2) hormones, 3) the prefrontal cortex, and 4) metabolites in male and female mice. We also studied the effect of three weeks of standard light-dark cycle restoration after five weeks of DD on the parameters mentioned above. We found that DD exposure was associated with anxiety-like behavior, increased corticosterone and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), downregulated neurotrophins (BDNF and NGF), and altered metabolites profile in a duration of DD exposure and sex-dependent manner. Females showed a more robust adaptation than males under DD exposure. Three weeks of restoration was adequate to establish homeostasis in both sexes. To the best of our knowledge, this study is the first of its kind to look at how DD exposure impacts physiology and behavior as a function of sex- and time. These findings would have translational value and may help in establishing sex-specific interventions for addressing DD-related psychological issues.PMID:36966879 | DOI:10.1016/j.neuroscience.2023.03.016

Transplant Cell Ther. 2023 Mar 24:S2666-6367(23)01196-X. doi: 10.1016/j.jtct.2023.03.020. Online ahead of print.ABSTRACTAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is used in the treatment of high-risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), however, the treatment has high risk of severe transplant-related mortality (TRM). In this study, we examined pretransplant serum samples derived from 92 consecutive allotransplant recipients with AML or MDS. Using non-targeted metabolomics, we identified 1274 metabolites including 968 of known identity (named biochemicals). We further investigated metabolites that differed significantly when comparing patients with and without early extensive fluid retention, pretransplant inflammation (both being associated with increased risk of acute graft-versus-host disease (GVHD)/nonrelapse mortality) and development of systemic steroid-requiring acute GVHD (aGVHD). All three factors are associated with TRM and were also associated with significantly altered amino acid metabolism, though there was only a minor overlap between these three factors with regard to significantly altered individual metabolites. Furthermore, steroid-requiring aGVHD was especially associated with altered taurine/hypotaurine, tryptophan, biotin, and phenylacetate metabolism together with altered malate-aspartate shuttle and urea cycle regulation. In contrast, pretransplant inflammation was associated with a weaker modulation of many different metabolic pathways, whereas extensive fluid retention was associated with a weaker modulation of taurine/hypotaurine metabolism. An unsupervised hierarchical cluster analysis based on the 13 most significantly identified metabolites associated with aGVHD identified a patient subset with high metabolite levels and increased frequencies of MDS/MDS-AML, steroid-requiring aGVHD and early TRM. On the other hand, a clustering analysis based on metabolites that were significantly altered for aGVHD, inflammation and fluid retention comparison groups identified a patient subset with a highly significant association with TRM. Our study suggests that the systemic pretransplant metabolic profiles can be used to identify patient subsets with an increased frequency of TRM.PMID:36966869 | DOI:10.1016/j.jtct.2023.03.020

Curr Opin Chem Biol. 2023 Mar 24;74:102288. doi: 10.1016/j.cbpa.2023.102288. Online ahead of print.ABSTRACTThe computational metabolomics field brings together computer scientists, bioinformaticians, chemists, clinicians, and biologists to maximize the impact of metabolomics across a wide array of scientific and medical disciplines. The field continues to expand as modern instrumentation produces datasets with increasing complexity, resolution, and sensitivity. These datasets must be processed, annotated, modeled, and interpreted to enable biological insight. Techniques for visualization, integration (within or between omics), and interpretation of metabolomics data have evolved along with innovation in the databases and knowledge resources required to aid understanding. In this review, we highlight recent advances in the field and reflect on opportunities and innovations in response to the most pressing challenges. This review was compiled from discussions from the 2022 Dagstuhl seminar entitled "Computational Metabolomics: From Spectra to Knowledge".PMID:36966702 | DOI:10.1016/j.cbpa.2023.102288

Environ Int. 2023 Mar 21;174:107896. doi: 10.1016/j.envint.2023.107896. Online ahead of print.ABSTRACTBenzotriazole ultraviolet stabilizers (BUVSs) are emerging pollutants that are widely detected in aquatic ecosystems. While structure-dependent effects of BUVSs are reported, the relationship between biotransformation and toxicity outcomes remains unclear. In this study, zebrafish embryos were exposed to two common BUVSs (UV-234 and UV-326) at 1, 10, and 100 µg/L for up to 7 days. Comparison of their uptake and biotransformation revealed that the bioaccumulation capacity of UV-234 was higher than that of UV-326, while UV-326 was more extensively biotransformed with additional conjugation reactions. However, UV-326 showed low metabolism due to inhibited phase II enzymes, which may result in the comparable internal concentrations of both BUVSs in larval zebrafish. Both BUVSs induced oxidative stress while decreased MDA, suggesting the disturbance of lipid metabolism. The subsequent metabolomic profiling revealed that UV-234 and UV-326 exerted different effects on arachidonic acid, lipid, and energy metabolism. However, both BUVSs negatively impacted the cyclic guanosine monophosphate / protein kinase G pathway. This converged metabolic change resulted in comparable toxicity of UV-234 and UV-326, which was confirmed by the induction of downstream apoptosis, neuroinflammation, and abnormal locomotion behavior. These data have important implications for understanding the metabolism, disposition, and toxicology of BUVSs in aquatic organisms.PMID:36966637 | DOI:10.1016/j.envint.2023.107896

J Med Chem. 2023 Mar 26. doi: 10.1021/acs.jmedchem.2c02000. Online ahead of print.ABSTRACTPhotoactive antibacterial therapy is one of the novel therapeutic methods that has great application potential and prospects for curbing bacterial infections. In this work, a photoactivated iridium complex (Ir-Cl) is synthesized for photoactive antibacterial research. Ir-Cl exhibits photoacidolysis, which can generate H+ and be converted into a photolysis product Ir-OH under blue light irradiation. At the meantime, this process is accompanied by 1O2 generation. Notably, Ir-Cl can selectively permeate S. aureus and exhibit excellent photoactive antibacterial activity. Mechanism studies show that Ir-Cl can ablate bacterial membranes and biofilms under light irradiation. Metabolomics analysis proves that Ir-Cl with light exposure mainly disturbs some amino acids' degradation (e.g., valine, leucine, isoleucine, arginine) and pyrimidine metabolism, which indirectly causes the ablation of biofilms and ultimately produces irreversible damage to S. aureus. This work provides guidance for metal complexes in antibacterial application.PMID:36966514 | DOI:10.1021/acs.jmedchem.2c02000

Mol Cell Biochem. 2023 Mar 26. doi: 10.1007/s11010-023-04713-3. Online ahead of print.ABSTRACTMALDI imaging for metabolites and immunohistochemistry for 38 immune markers was used to characterize the spatial biology of 2 primary oral tumours, one from a patient with an early recurrence (Tumour R), and the other from a patient with no recurrence 2 years after treatment completion (Tumour NR). Tumour R had an increased purine nucleotide metabolism in different regions of tumour and adenosine-mediated suppression of immune cells compared to Tumour NR. The differentially expressed markers in the different spatial locations in tumour R were CD33, CD163, TGF-β, COX2, PD-L1, CD8 and CD20. These results suggest that altered tumour metabolomics concomitant with a modified immune microenvironment could be a potential marker of recurrence.PMID:36966422 | DOI:10.1007/s11010-023-04713-3

Commun Biol. 2023 Mar 25;6(1):323. doi: 10.1038/s42003-023-04693-6.ABSTRACTThe nuclear factor-κB (NF-κB) signaling pathway regulates specific immunological responses and controls a wide range of physiological processes. NF-κB inhibitor alpha (IKBA) is an NF-κB inhibitory mediator in the cytoplasm that modulates the nuclear translocation and DNA binding activities of NF-κB proteins. However, whether the upstream cascade of the canonical NF-κB signaling pathway has physiological roles independent of IKBA-mediated transcriptional activation remains unclear. Herein we investigated the function of IKBA in mature sperm in which transcriptional and translational events do not occur. IKBA was highly expressed in human sperm. The repression of IKBA phosphorylation by its inhibitor Bay117082 markedly enhanced sperm motility. On the contrary, lipopolysaccharide-stimulated IKBA phosphorylation significantly decreased sperm motility. Nevertheless, Bay117082 treatment did not affect the motility of IKBA-knockout sperm. Further, untargeted metabolomic analysis and pharmacological blocking assays revealed that the Bay117082-induced increase in sperm motility was attributable to fatty acid β-oxidation (FAO) enhancement. In addition, we found that IKBA phosphorylation inhibition resulted in a significant reduction of acetyl-CoA carboxylase levels in the FAO metabolic pathway. Our findings indicate that IKBA-mediated signaling orchestrates sperm motility program and improves our understanding of transcription-independent NF-κB signaling pathway in cells.PMID:36966253 | DOI:10.1038/s42003-023-04693-6