PubMed

Am J Physiol Endocrinol Metab. 2023 Feb 1. doi: 10.1152/ajpendo.00231.2022. Online ahead of print.ABSTRACTObesity is one of the leading non-communicable diseases in the world. Despite intense efforts to develop strategies to prevent and treat obesity, its prevalence continues to rise worldwide. A recent study has shown that the tricarboxylic acid intermediate succinate increases body energy expenditure by promoting brown adipose tissue thermogenesis through the activation of uncoupling protein-1; this has generated interest surrounding its potential usefulness as an approach to treat obesity. It is currently unknown how succinate impacts brown adipose tissue protein expression, and how exogenous succinate impacts body mass reduction promoted by a drug approved to treat human obesity, the glucagon-like-1 receptor agonist, liraglutide. In the first part of this study, we used bottom-up shotgun proteomics to determine the acute impact of exogenous succinate on the brown adipose tissue. We show that succinate rapidly affects the expression of 177 brown adipose tissue proteins, which are mostly associated with mitochondrial structure and function. In the second part of this study, we performed a short-term preclinical pharmacological intervention, treating diet-induced obese mice with a combination of exogenous succinate and liraglutide. We show that the combination was more efficient than liraglutide alone in promoting body mass reduction, food energy efficiency reduction, food intake reduction and an increase in body temperature. Using serum metabolomics analysis, we showed that succinate, but not liraglutide, promoted a significant increase in the blood levels of several medium- and long-chain fatty acids. In conclusion, exogenous succinate promotes rapid changes in brown adipose tissue mitochondrial proteins, and when used in association with liraglutide, increases body mass reduction.PMID:36724126 | DOI:10.1152/ajpendo.00231.2022

J Urol. 2023 Feb 1:101097JU0000000000003200. doi: 10.1097/JU.0000000000003200. Online ahead of print.ABSTRACTOBJECTIVE: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro.MATERIAL AND METHODS: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, PTFE, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation.RESULTS: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma), and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least).CONCLUSIONS: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.PMID:36724057 | DOI:10.1097/JU.0000000000003200

Curr Microbiol. 2023 Feb 1;80(3):90. doi: 10.1007/s00284-023-03195-2.ABSTRACTThis study investigated the bacterial and postbiotic potential of three Anatolian bee bread samples obtained from different regions of Turkey (Marmara, Aegean, and Mediterranean) and offered for human consumption. The families most commonly found in Anatolian bee bread were Lactobacillaceae, Oscillospiraceae, Bacteroidaceae, Prevotellaceae, and Lachnospiraceae. Lactobacillus delbruckeii was highly abundant, but also other beneficial bacteria, known to be next-generation probiotics, were revealed in bee bread, such as Prevotalla copri, Faecalibacterium prausnitzii, and Akkermansia muciniphila. Apart from these beneficial bacteria, bee bread samples also harbored undesired bacteria such as Phocaeicola vulgatus, Phocaeicola dorei, and Clostridium perfringens. Fatty acid composition showed that bee bread samples had butyric acid, a short-chain fatty acid, as a postbiotic. Additionally, polyunsaturated fatty acids were also found such as alfa-linolenic acid and eicosadienoic acid. The fatty acids with the highest amounts were palmitic acid (~ 30%), stearic acid (~ 17%), and alpha-linolenic acid (~ 12%). One of the samples exhibited antimicrobial activity against Staphylococcus aureus.PMID:36723722 | DOI:10.1007/s00284-023-03195-2

Clin Oral Investig. 2023 Feb 1. doi: 10.1007/s00784-023-04878-7. Online ahead of print.ABSTRACTThe interface of molecular science and technology is guiding the transformation of personalized to precision healthcare. The application of proteomics, genomics, transcriptomics, and metabolomics is shaping the suitability of biomarkers for disease. Prior validation of such biomarkers in large and diverse patient cohorts helps verify their clinical usability. Incorporation of molecular discoveries into routine clinical practice relies on the development of customized assays and devices that enable the rapid delivery of analytical data to the clinician, while the patient is still in session. The present perspective review addresses this topic under the prism of precision periodontal care. Selected promising research attempts to innovate technological platforms for oral diagnostics are brought forward. Focus is placed on (a) the suitability of saliva as a conveniently sampled biological specimen for assessing periodontal health, (b) proteomics as a high-throughput approach for periodontal disease biomarker identification, and (c) chairside molecular diagnostic assays as a technological funnel for transitioning from the laboratory benchtop to the clinical point-of-care.PMID:36723713 | DOI:10.1007/s00784-023-04878-7

Phytother Res. 2023 Feb 1. doi: 10.1002/ptr.7704. Online ahead of print.ABSTRACTNeuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.PMID:36723382 | DOI:10.1002/ptr.7704

Anal Methods. 2023 Feb 1. doi: 10.1039/d2ay01446g. Online ahead of print.ABSTRACTAspergillus fumigatus has the potential to degrade lignocellulosic biomass, but the degradation mechanism is not clear. The purpose of this study is to analyze the differential proteins and metabolites produced by Aspergillus fumigatus G-13 in the degradation of different lignin model compounds. Ferulic acid, sinapic acid, and p-coumaric acid were used as carbon sources. By controlling the culture conditions, and adding a cellulose co-substrate and an auxiliary carbon source, the enzymatic production law of three lignin model compounds degraded by Aspergillus fumigatus G-13 was investigated. Proteomics and metabolomics analysis were conducted for the two groups with the largest difference in enzyme activity expression. The results showed that a total of 1447 peptides were identified by proteomics analysis. Among them, 134 proteins were significantly changed, 73 proteins were up-regulated, and 61 proteins were down-regulated. The key proteins that degrade lignin model compounds are catechol dioxygenase, glutathione reductase, dextranase, isoamyl alcohol oxidase, glyceraldehyde-3-phosphate dehydrogenase and superoxide dismutase. Enrichment analysis of differential metabolite functions revealed that Aspergillus fumigatus G-13 is associated with several pathways related to the degradation of lignin. Among them, starch and sucrose metabolism, pentose phosphate pathway, glutathione metabolism, and the ortho-cleavage pathway of dihydroxylated aromatic rings are closely related to lignin degradation. The information presented in this paper will be helpful for future research on the degradation or depolymerization of natural lignocellulosic substrates.PMID:36723181 | DOI:10.1039/d2ay01446g

Schizophr Bull. 2023 Feb 1:sbac202. doi: 10.1093/schbul/sbac202. Online ahead of print.ABSTRACTBACKGROUND AND HYPOTHESIS: Antipsychotics (APs), the cornerstone of schizophrenia treatment, confer a relatively high risk of constipation. However, the mechanisms underpinning AP-induced constipation are poorly understood. Thus, we hypothesized that (1) schizophrenia patients with AP-induced constipation have distinct metabolic patterns; (2) there is more than one mechanism at play in producing this adverse drug effect; and (3) AP-associated changes in the gut microbiome are related to the altered metabolic profiles.STUDY DESIGN: Eighty-eight schizophrenia patients, including 44 with constipation (C) and 44 matched patients without constipation (NC), were enrolled in this study. Constipation was diagnosed by Rome IV criteria for constipation and colonic transit time using radiopaque markers (ROMs) while severity was evaluated with the Bristol Stool Form Scale (BSS) and Constipation Assessment Scale (CAS). Fasting blood samples were drawn from all participants and were subjected to non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis.STUDY RESULTS: Eleven metabolites were significantly altered in AP-induced constipation which primarily disturbed sphingolipid metabolism, choline metabolism, and sphingolipid signaling pathway (P value < .05, FDR < 0.05). In the C group, changes in the gut bacteria showed a certain degree of correlation with 2 of the significantly altered serum metabolites and were associated with alterations in choline metabolism.CONCLUSIONS: Our findings indicated that there were disturbances in distinct metabolic pathways that were associated with AP-induced constipation. In addition, this study presents evidence of a link between alterations in the gut microbiome and host metabolism which provides additional mechanistic insights on AP-induced constipation.PMID:36723169 | DOI:10.1093/schbul/sbac202

Mol Omics. 2023 Jan 30. doi: 10.1039/d2mo00220e. Online ahead of print.ABSTRACTCisplatin is commonly used in combination with other cytotoxic agents as a standard treatment regimen for a variety of solid tumors, such as lung, ovarian, testicular, and head and neck cancers. However, the effectiveness of cisplatin is accompanied by toxic side effects, for instance, nephrotoxicity and neurotoxicity. The response of tumors to cisplatin treatment involves multiple physiological processes, and the efficacy of chemotherapy is limited by the intrinsic and acquired resistance of tumor cells. Although enormous efforts have been made toward molecular mechanisms of cisplatin resistance, the development of omics provides new insights into the understanding of cisplatin resistance at genome, transcriptome, proteome, metabolome and epigenome levels. Mechanism studies using different omics approaches revealed the necessity of multi-omics applications, which provide information at different cellular function levels and expand our recognition of the peculiar genetic and phenotypic heterogeneity of cancer. The present work systematically describes the underlying mechanisms of cisplatin resistance in different tumor types using multi-omics approaches. In addition to the classical mechanisms such as enhanced drug efflux, increased DNA damage repair and changes in the cell cycle and apoptotic pathways, other changes like increased protein damage clearance, increased protein glycosylation, enhanced glycolytic process, dysregulation of the oxidative phosphorylation pathway, ferroptosis suppression and mRNA m6A methylation modification can also induce cisplatin resistance. Therefore, utilizing the integrated omics to identify key signaling pathways, target genes and biomarkers that regulate chemoresistance are essential for the development of new drugs or strategies to restore tumor sensitivity to cisplatin.PMID:36723121 | DOI:10.1039/d2mo00220e

Microbiol Spectr. 2023 Feb 1:e0327522. doi: 10.1128/spectrum.03275-22. Online ahead of print.ABSTRACTWe compared changes induced by the addition of 100 nM and 5 mM glucose on the proteome and metabolome complements in Synechococcus sp. strains WH8102, WH7803, and BL107 and Prochlorococcus sp. strains MED4, SS120, and MIT9313, grown either under standard light conditions or in darkness. Our results suggested that glucose is metabolized by these cyanobacteria, using primarily the oxidative pentoses and Calvin pathways, while no proof was found for the involvement of the Entner-Doudoroff pathway in this process. We observed differences in the effects of glucose availability, both between genera and between Prochlorococcus MED4 and SS120 strains, which might be related to their specific adaptations to the environment. We found evidence for fermentation in Prochlorococcus sp. strain SS120 and Synechococcus sp. strain WH8102 after 5 mM glucose addition. Our results additionally suggested that marine cyanobacteria can detect nanomolar glucose concentrations in the environment and that glucose might be used to sustain metabolism under darkness. Furthermore, the KaiB and KaiC proteins were also affected in Synechococcus sp. WH8102, pointing to a direct link between glucose assimilation and circadian rhythms in marine cyanobacteria. In conclusion, our study provides a wide overview on the metabolic effects induced by glucose availability in representative strains of the diverse marine picocyanobacteria, providing further evidence for the importance of mixotrophy in marine picocyanobacteria. IMPORTANCE Glucose uptake by marine picocyanobacteria has been previously described and strongly suggests they are mixotrophic organisms (capable of using energy from the sun to make organic matter, but also to directly use organic matter from the environment when available). However, a detailed analysis of the effects of glucose addition on the proteome and metabolome of these microorganisms had not been carried out. Here, we analyzed three Prochlorococcus sp. and three Synechococcus sp. strains which were representative of several marine picocyanobacterial clades. We observed differential features in the effects of glucose availability, depending on both the genus and strain; our study illuminated the strategies utilized by these organisms to metabolize glucose and showed unexpected links to other pathways, such as circadian regulation. Furthermore, we found glucose addition had profound effects in the microbiome, favoring the growth of coexisting heterotrophic bacteria.PMID:36722960 | DOI:10.1128/spectrum.03275-22

Food Funct. 2023 Jan 26. doi: 10.1039/d2fo03277e. Online ahead of print.ABSTRACTDepression is the most prevalent psychiatric disease, and its pathogenesis is still unclear. Currently, studies on the pathogenesis of depression are mainly focused on the brain. The liver can modulate brain function via the liver-brain axis, indicating that the liver plays an important role in the development of depression. This study aims to explore the protective effect of quercetin against chronic unpredictable mild stress (CUMS)-induced metabolic changes and the corresponding mechanisms in the rat liver based on untargeted metabolomics technology. In this study, 96 male rats were divided into six groups: control, different doses of quercetin (10 mg per kg bw or 50 mg per kg bw), CUMS, and CUMS + different doses of quercetin. After 8 weeks of CUMS modeling, the liver samples were collected for metabolomics analysis. A total of 17 altered metabolites were identified, including D-glutamic acid, S-adenosylmethionine, lithocholylglycine, L-homocystine, prostaglandin PGE2, leukotriene E4, cholic acid, 5-methyltetrahydrofolic acid, taurochenodeoxycholic acid, S-adenosylhomocysteine, deoxycholic acid, folic acid, L-methionine, leukotriene C5, estriol-17-glucuronide, PE, and PC, indicating that methionine metabolism, bile acid metabolism, and phosphatidylcholine biosynthesis are the major pathways involved in CUMS-induced hepatic metabolic disorders. Hepatic methylation damage may play a role in the pathophysiology of depression, as evidenced by the first discovery of the abnormality of hepatic methionine metabolism. Abnormal changes in hepatic bile acids may provide stronger evidence for depression pathogenesis involving the microbiota-gut-brain axis, suggesting that the liver is involved in depression development and may be a treatment target. The quercetin treatment alleviated the CUMS-induced liver metabolism disorder, suggesting that quercetin may protect against depression by regulating liver metabolism.PMID:36722921 | DOI:10.1039/d2fo03277e

Singapore Med J. 2023 Jan;64(1):45-52. doi: 10.4103/singaporemedj.SMJ-2021-432.ABSTRACTMicrobiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.PMID:36722516 | DOI:10.4103/singaporemedj.SMJ-2021-432

J Proteome Res. 2023 Feb 1. doi: 10.1021/acs.jproteome.2c00295. Online ahead of print.ABSTRACTGastric cancer (GAS) is one of the malignant tumors of the gastrointestinal system. Alterations in metabolite composition can reflect pathological processes of GAS and constitute a basis for diagnosis and treatment improvements. In this study, a total of 301 serum samples from 150 GAS patients at different tumor-node-metastasis (TNM) stages and 151 healthy controls were collected. Mass spectrometry platforms were performed to investigate the changes in GAS-related metabolites and explore the new potential serum biomarkers and the metabolic dysregulation associated with GAS progression. Twelve differential metabolites (ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate, D-urobilinogen, 14-HDoHE, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid, 5,6-dihydroxyprostaglandin F1a, 9'-carboxy-gamma-tocotrienol, glutaric acid, alanine, tyrosine, C18:2(FFA), adipic acid, and suberic acid) were identified to establish the diagnosis model for GAS. The defined biomarker panel was also statistically significant for GAS progression with different TNM stages. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment revealed the metabolic dysregulation associated with GAS progression. In conclusion, a diagnostic panel was established and validated, which could be used to further stage the early and advanced GAS patients from healthy controls. These findings may provide useful information for explaining the GAS metabolic alterations and try to facilitate the characterization of GAS patients in the early stage.PMID:36722497 | DOI:10.1021/acs.jproteome.2c00295

J Sci Food Agric. 2023 Feb 1. doi: 10.1002/jsfa.12477. Online ahead of print.ABSTRACTBACKGROUND: Sheep whey protein (SWP), Fu brick tea polysaccharides (FBTP) and stachyose (STA) have been shown to improve immunity, but little is known about the regulatory effect of SWP, FBTP, STA and their combined formula (CF) on immune function and intestinal metabolism of immunosuppressed mice induced by cyclophosphamide (CTX).RESULTS: Administration of SWP, FBTP, STA or CF restored the levels of body weight, immune organ index, immune organ morphology, cytokines and immunoglobulins in CTX immunosuppressed mice. Interestingly, CF improved all the mentioned parameters more effective than administration of SWP, FBTP or STA alone. In addition, CF was more effective to increase the levels of intestinal immune-related gene expression than FBTP, SWP or STA alone in immunosuppressed mice, suggesting that CF exhibited excellent intestinal immune regulation function. CF also significantly improved cecal concentrations of short-chain fatty acids of CTX-treated mice. Furthermore, metabolomics analysis demonstrated that CF recovered the levels 28 metabolites associated with the CTX treatment to the levels of normal mice.CONCLUSION: Conclusively, these findings suggested that CF as a functional food combination of SWP, FBTP and STA could promote the immune function to against human diseases, which providing theoretical support for the co-ingestion of sheep whey protein and functional sugars as a feasible strategy for improving the body immunity in the future. This article is protected by copyright. All rights reserved.PMID:36722467 | DOI:10.1002/jsfa.12477

Plant Physiol. 2023 Feb 1:kiad064. doi: 10.1093/plphys/kiad064. Online ahead of print.ABSTRACTPeel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on post-harvest storage, while studies at the pre-harvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that pre-harvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the pre-harvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid (Y1H) assay, electrophoretic mobility shift assay (EMSA), luciferase (LUC) reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating pre-harvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.PMID:36722358 | DOI:10.1093/plphys/kiad064

J Integr Neurosci. 2023 Jan 11;22(1):13. doi: 10.31083/j.jin2201013.ABSTRACTBACKGROUND: A close relationship exists between major depressive disorder (MDD) and diabetes mellitus. The metabolomic difference and similarity between patients with and without diabetes mellitus have not been well studied in the context of MDD. We aimed to examine these differences and common serum metabolomics patterns, pathways and biomarkers that can comprehensively reflect the pathogenetic difference and similarity between these MDD groups.METHODS: We performed a metabolomics analysis of serum samples of healthy controls (n = 6), patients with MDD and type 2 diabetes mellitus (n = 13), and patients with MDD without type 2 diabetes mellitus (n = 27). Metabolomics analysis was conducted using capillary electrophoresis Fourier transform mass spectrometry and a candidate compound was assigned to the 496 (290 cation, 206 anion) peaks. Moreover, we evaluated the sensitivity and specificity of the candidate biomarkers for distinguishing between MDD patients with or without type 2 diabetes mellitus.RESULTS: Principal component analysis revealed no clear distinction among the three groups, while naive partial least squares discriminant analysis yielded three relatively good and distinct populations based on the first principal component. Energy conversion by the tricarboxylic acid cycle represented the highest percentage among the top 30 positive factors of the first principal component, and glutamate metabolism and urea cycle represented the highest percentage among the top 30 negative factors of the first principal component. Synthesis and degradation of ketone bodies had high impact in MDD with type 2 diabetes mellitus group and taurine and hypotaurine metabolism had high impact in MDD without type 2 diabetes mellitus group for the pathway.CONCLUSIONS: Patterns of serum metabolites may be different among MDD with type 2 diabetes mellitus, MDD without type 2 diabetes mellitus, and healthy controls groups. Specifically, comorbid type 2 diabetes mellitus could affect metabolomics pathway and alter the distribution of serum metabolites in patients with MDD. These findings may shed light on the influence of the type 2 diabetes on the pathophysiology of MDD.PMID:36722244 | DOI:10.31083/j.jin2201013

Aesthet Surg J. 2023 Feb 1:sjad018. doi: 10.1093/asj/sjad018. Online ahead of print.ABSTRACTBACKGROUND: Photobiomodulation (PBM) therapy is an increasingly popular modality for aesthetic skin rejuvenation. PBM induces genomic, proteomic and metabolomic processes within target cells but such manipulation of cell behavior has led to concerns about oncologic safety.OBJECTIVES: This article presents a summary of the clinical and pre-clinical evidence for the oncologic safety of PBM for aesthetic skin rejuvenation.METHODS: A focused systematic review was performed, wherein safety data from clinical trials of PBM for skin rejuvenation was supplemented by analyses of in vitro data using cells derived from human skin and human neoplastic cells and in vivo data of tumors of the skin, oral cavity and breast.RESULTS: Within established parameters, red/near infrared light mainly enhances proliferation of healthy cells without a clear pattern of influence on cell viability. The same light parameters mainly reduce neoplastic cell proliferation and viability or else make no difference. Invasiveness potential (appraised by cell migration assays and/or differential gene expression) is equivocal. PBM does not induce dysplastic change in healthy cells. In vivo tumor models yield varied results with no clear pattern emerging. There are no relevant clinical trials data linking PBM with any significant adverse events including the finding of a new or recurrent malignancy.CONCLUSIONS: Current clinical and pre-clinical evidence suggests that PBM is oncologically safe for skin rejuvenation and there is no evidence to support the proposition that it should be avoided by patients who have previously undergone treatment for cancer.PMID:36722207 | DOI:10.1093/asj/sjad018

Plant Physiol. 2023 Feb 1:kiad052. doi: 10.1093/plphys/kiad052. Online ahead of print.ABSTRACTManganese (Mn) is an essential metal for plant growth. The most important Mn-containing enzyme is the Mn4CaO5 cluster that catalyzes water oxidation in Photosystem II. Mn deficiency primarily affects photosynthesis, while Mn excess is generally toxic. Here, we studied Mn excess and deficiency in the liverwort Marchantia polymorpha, an emerging model ideally suited for analysis of metal stress since it accumulates rapidly toxic substances due to the absence of well-developed vascular and radicular systems and a reduced cuticle. We established growth conditions for Mn excess and deficiency and analyzed the metal content in thalli and isolated chloroplasts. In vivo super-resolution fluorescence microscopy and transmission electron microscopy revealed changes in the organization of the thylakoid membrane under Mn excess and deficiency. Both Mn excess and Mn deficiency increased the stacking of the thylakoid membrane. We investigated photosynthetic performance by measuring chlorophyll fluorescence at room temperature and 77 K, measuring P700 absorbance, and studying the susceptibility of thalli to photoinhibition. Non-optimal Mn concentrations changed the ratio of photosystem I to photosystem II. Upon Mn deficiency, higher non-photochemical quenching was observed, electron donation to photosystem I was favored, and photosystem II was less susceptible to photoinhibition. Mn deficiency seemed to favor cyclic electron flow around photosystem I, thereby protecting photosystem II in high light. The results presented here suggest an important role of Mn for the organization of the thylakoid membrane and photosynthetic electron transport.PMID:36722179 | DOI:10.1093/plphys/kiad052

Biol Reprod. 2023 Jan 31:ioad014. doi: 10.1093/biolre/ioad014. Online ahead of print.ABSTRACTIncreasing evidences showed ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome(LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF and PF. GCs from endometriosis patients revealed decreased expression of HPGD, COX-2 and suppressed NF-кB signaling. Similarly, progesterone treatment in vitro down-regulated HPGD and COX2 expression and suppressed NF-кB signaling in granulosa tumor-like cell line KGN (Bena culture collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIкBα/IкBα ratio and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIкBα, p65 and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found intrafollicular progesterone might down-regulate HPGD and COX-2 in GCs via suppressing the NF-кB signaling pathway, shedding light on the mechanism underlying the endometriosis related ovulatory dysfunction.PMID:36721997 | DOI:10.1093/biolre/ioad014

Rapid Commun Mass Spectrom. 2023 Jan 31:e9481. doi: 10.1002/rcm.9481. Online ahead of print.ABSTRACTRATIONALE: The chemical constituent of Chinese patent medicine is usually different from crude medicine because of specific preparation process. Chimonanthus nitens Oliv. leaf granule is widely used for prevention against Covid-19 in China. However, none research on chemical constituents of the granule and their variation during the preparation process is reported.METHODS: Fragmentation rules of reference compounds were investigated in electrospray ionization mass spectrometry, new gas phase reaction was rationalized via electronic and steric effect, and calculated chemistry. Then, a strategy based on new fragmentation patterns was conducted to profile aromatic constituents. Additionally, basing on untargeted metabolomics analytical workflow, comparison on chemical constituents of leaf and granule was performed.RESULTS: New fragmentation patterns related to two competing reactions, ring-opening and ring-closing reaction for coumarin have been proposed and been rationalized intensely. New established diagnostic ion at m/z 81.0331 worked powerfully in assignment of OH-7 and substituent at C-8 of coumarin. McLafferty rearrangement occurring to coumarin glycoside with sugar group at C-4 was firstly observed, and newly formed dialogue ions at m/z 147.0440, 119.0488 and 91.0543.CONCLUSIONS: Aromatic constituents of the granule were firstly profiled. A total of 114 aromatic compounds were identified, of those 85 compounds were firstly discovered. The kaempferol-7-O-neohesperidoside and its homologues were mostly enriched in the granule. Considering their reported bioactivities, these analogues possibly contribute greatly to clinical efficacy. Our present results offered new fragmentation theory for coumarins and new material basis for quality control of the granule.PMID:36721310 | DOI:10.1002/rcm.9481

Microbiome. 2023 Jan 31;11(1):19. doi: 10.1186/s40168-022-01458-x.ABSTRACTBACKGROUND: Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown.OBJECTIVE: In the present study, we aimed to investigate the metabolism, therapeutic potential, and mechanisms of action of bile acids (BAs) in LBW-induced intestinal inflammation in a piglet model.METHODS: The fecal microbiome and BA profile between LBW and normal birth weight (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed to further confirm the linkage between microbial BA metabolism and intestinal inflammation. The therapeutic potential of ursodeoxycholic acid (UDCA), a highly differentially abundant BA between LBW and NBW piglets, in alleviating colonic inflammation was evaluated in both LBW piglets, an LBW-FMT mice model, and a DSS-induced colitis mouse model. The underlying cellular and molecular mechanisms by which UDCA suppresses intestinal inflammation were also investigated in both DSS-treated mice and a macrophage cell line. Microbiomes were analyzed by using 16S ribosomal RNA sequencing. Fecal and intestinal BA profiles were measured by using targeted BA metabolomics. Levels of farnesoid X receptor (FXR) were knocked down in J774A.1 cells with small interfering RNAs.RESULTS: We show a significant difference in both the fecal microbiome and BA profiles between LBW and normal birth weight animals in a piglet model. Transplantation of the microbiota of LBW piglets to antibiotic-treated mice leads to intestinal inflammation. Importantly, oral administration of UDCA, a major BA diminished in the intestinal tract of LBW piglets, markedly alleviates intestinal inflammation in LBW piglets, an LBW-FMT mice model, and a mouse model of colitis by inducing M2 macrophage polarization. Mechanistically, UDCA reduces inflammatory cytokine production by engaging BA receptor FXR while suppressing NF-κB activation in macrophages.CONCLUSIONS: These findings establish a causal relationship between LBW-associated intestinal abnormalities and dysbiosis, suggesting that restoring intestinal health and postnatal maldevelopment of LBW infants may be achieved by targeting intestinal microbiota and BA metabolism. Video Abstract.PMID:36721210 | DOI:10.1186/s40168-022-01458-x