Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Multi-omics analysis reveals genes and metabolites involved in <em>Bifidobacterium pseudocatenulatum</em> biofilm formation

Wed, 29/11/2023 - 12:00
Front Microbiol. 2023 Nov 9;14:1287680. doi: 10.3389/fmicb.2023.1287680. eCollection 2023.ABSTRACTBacterial biofilm is an emerging form of life that involves cell populations living embedded in a self-produced matrix of extracellular polymeric substances (EPS). Currently, little is known about the molecular mechanisms of Bifidobacterium biofilm formation. We used the Bifidobacterium biofilm fermentation system to preparation of biofilms on wheat fibers, and multi-omics analysis of both B. pseudocatenulatum biofilms and planktonic cells were performed to identify genes and metabolites involved in biofilm formation. The average diameter of wheat fibers was around 50 μm, while the diameter of particle in wheat fibers culture of B. pseudocatenulatum was over 260 μm at 22 h with 78.96% biofilm formation rate (BR), and the field emission scanning electron microscopy (FESEM) results showed that biofilm cells on the surface of wheat fibers secreted EPS. Transcriptomic analysis indicated that genes associated with stress response (groS, mntH, nth, pdtaR, pstA, pstC, radA, rbpA, whiB, ybjG), quorum sensing (dppC, livM, luxS, sapF), polysaccharide metabolic process (rfbX, galE, zwf, opcA, glgC, glgP, gtfA) may be involved in biofilm formation. In addition, 17 weighted gene co-expression network analysis (WGCNA) modules were identified and two of them positively correlated to BR. Metabolomic analysis indicated that amino acids and amides; organic acids, alcohols and esters; and sugar (trehalose-6-phosphate, uridine diphosphategalactose, uridine diphosphate-N-acetylglucosamine) were main metabolites during biofilm formation. These results indicate that stress response, quorum sensing (QS), and EPS production are essential during B. pseudocatenulatum biofilm formation.PMID:38029154 | PMC:PMC10666050 | DOI:10.3389/fmicb.2023.1287680

Metabolomic profiling of Marek's disease virus infection in host cell based on untargeted LC-MS

Wed, 29/11/2023 - 12:00
Front Microbiol. 2023 Nov 9;14:1270762. doi: 10.3389/fmicb.2023.1270762. eCollection 2023.ABSTRACTMarek's disease (MD) caused by Marek's disease virus (MDV), poses a serious threat to the poultry industry by inducing neurological disease and malignant lymphoma in infected chickens. However, the underlying mechanisms how MDV disrupts host cells and causes damage still remain elusive. Recently, the application of metabolomics has shown great potential for uncovering the complex mechanisms during virus-host interactions. In this study, chicken embryo fibroblasts (CEFs) infected with MDV were subjected to ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) and multivariate statistical analysis. The results showed that 261 metabolites were significantly altered upon MDV infection, with most changes occurring in amino acid metabolism, energy metabolism, nucleotide metabolism, and lipid metabolism. Notably, MDV infection induces an up-regulation of amino acids in host cells during the early stages of infection to provide the energy and intermediary metabolites necessary for efficient multiplication of its own replication. Taken together, these data not only hold promise in identifying the biochemical molecules utilized by MDV replication in host cells, but also provides a new insight into understanding MDV-host interactions.PMID:38029131 | PMC:PMC10666056 | DOI:10.3389/fmicb.2023.1270762

<em>pts</em> promoter influences antibiotic resistance via proton motive force and ROS in <em>Escherichia coli</em>

Wed, 29/11/2023 - 12:00
Front Microbiol. 2023 Nov 6;14:1276954. doi: 10.3389/fmicb.2023.1276954. eCollection 2023.ABSTRACTINTRODUCTION: Glucose level is related to antibiotic resistance. However, underlying mechanisms are largely unknown.METHODS: Since glucose transport is performed by phosphotransferase system (PTS) in bacteria, pts promoter-deleted K12 (Δpts-P) was used as a model to investigate effect of glucose metabolism on antibiotic resistance. Gas chromatography-mass spectrometry based metabolomics was employed to identify a differential metabolome in Δpts-P compared with K12, and with glucose as controls.RESULTS: Δpts-P exhibits the resistance to β-lactams and aminoglycosides but not to quinolones, tetracyclines, and macrolide antibiotics. Inactivated pyruvate cycle was determined as the most characteristic feature in Δpts-P, which may influence proton motive force (PMF), reactive oxygen species (ROS), and nitric oxide (NO) that are related to antibiotic resistance. Thus, they were regarded as three ways for the following study. Glucose promoted PMF and β-lactams-, aminoglycosides-, quinolones-mediated killing in K12, which was inhibited by carbonyl cyanide 3-chlorophenylhydrazone. Exogenous glucose did not elevated ROS in K12 and Δpts-P, but the loss of pts promoter reduced ROS by approximately 1/5, which was related to antibiotic resistance. However, NO was neither changed nor related to antibiotic resistance.DISCUSSION: These results reveal that pts promoter regulation confers antibiotic resistance via PMF and ROS in Escherichia coli.PMID:38029124 | PMC:PMC10661408 | DOI:10.3389/fmicb.2023.1276954

Alteration of lipopolysaccharide O antigen leads to avirulence of gut-colonizing <em>Serratia marcescens</em>

Wed, 29/11/2023 - 12:00
Front Microbiol. 2023 Nov 9;14:1278917. doi: 10.3389/fmicb.2023.1278917. eCollection 2023.ABSTRACTThe reason why the potent entomopathogen Serratia marcescens fails to kill insects through oral infection is unknown. To compare effects of septic injection and oral administration of S. marcescens, we used a model bean bug, Riptortus pedestris. Most R. pedestris insects survived oral infections, but not septic infections. Although the number of S. marcescens cells in hemolymph after oral infection, which were originated from gut-colonizing S. marcescens, was higher than the fatal number of cells used in septic injection, they did not kill host insects, suggesting a loss of virulence in gut-colonizing S. marcescens cells. When gut-colonizing S. marcescens cells were septically injected into insects, they failed to kill R. pedestris and survive in hemolymph. To understand the avirulence mechanisms in gut-colonizing bacteria, lipopolysaccharides of S. marcescens were analyzed and revealed that the O antigen was lost during gut colonization. Gut-colonizing S. marcescens cells were resistant to humoral immune responses but susceptible to cellular immune responses, easily succumbing to phagocytosis of hemocytes. When cellular immunity was suppressed, the gut-colonizing S. marcescens cells recovered their virulence and killed insects through septic injection. These results suggest that a key mechanism of avirulence in orally infected S. marcescens is the loss of the O antigen, resulting in susceptibility to host's cellular immune responses.PMID:38029092 | PMC:PMC10665507 | DOI:10.3389/fmicb.2023.1278917

Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration

Wed, 29/11/2023 - 12:00
Methodist Debakey Cardiovasc J. 2023 Nov 16;19(5):58-68. doi: 10.14797/mdcvj.1304. eCollection 2023.ABSTRACTExercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited during exercise. During exercise, skeletal muscle releases several myokines, including angiogenic factors and cytokines that drive tissue vascular regeneration via activation of endothelial cells, as well as by recruiting immune and endothelial progenitor cells. Some of these core exercise-activated pathways can be extrapolated to vascular regeneration in other organs. I also highlight future areas of exercise research (including metabolomics, single cell transcriptomics, and extracellular vesicle biology) to advance our understanding of how exercise induces vascular regeneration at the molecular level, and propose the idea of "exercise-mimicking" therapeutics for vascular recovery.PMID:38028974 | PMC:PMC10655757 | DOI:10.14797/mdcvj.1304

Lactate plasma level as a potential biomarker in early diagnosis of ectopic pregnancy: A case-control survey

Wed, 29/11/2023 - 12:00
Health Sci Rep. 2023 Nov 16;6(11):e1705. doi: 10.1002/hsr2.1705. eCollection 2023 Nov.ABSTRACTINTRODUCTION: A novel metabolomics survey proposed lactic acid as a diagnostic biomarker to detect ectopic pregnancy (EP). Here we investigate the plasma level of lactate for early diagnosis of EP as a potential biomarker.METHODS: In a case-control study, the reproductive aged women with definite tubal EP (6-10 weeks' gestation), referred to our department during 2021-2022, considered as case group, and women with normal singleton pregnancy in the same gestational age as control group. After informed concept, demographic data (maternal and gestational age and parity) recorded and 5 mL venous blood samples were taken to detect the lactate plasma level. The data analyzed using SPSS software ver22.RESULTS: Finally, 95 participations (50 in case and 45 in control group) enrolled. The clinical results showed that the most of case group were aged more than 35 years old with had higher parity and body mass index, but, no statistically significant difference showed up. On the other hand, although the lactate level was slightly higher in women with EP, but, the plasma lactate level did not statistically differ between the two study groups. Also, the logistic regression showed no relationship between the demographic variables and the lactate plasma level.CONCLUSION: It seems that the plasma level of lactate cannot be a diagnostic biomarker for EP.PMID:38028671 | PMC:PMC10654378 | DOI:10.1002/hsr2.1705

Interactions with microbial consortia have variable effects in organic carbon and production of exometabolites among genotypes of <em>Populus trichocarpa</em>

Wed, 29/11/2023 - 12:00
Plant Direct. 2023 Nov 21;7(11):e544. doi: 10.1002/pld3.544. eCollection 2023 Nov.ABSTRACTPoplar is a short-rotation woody crop frequently studied for its significance as a sustainable bioenergy source. The successful establishment of a poplar plantation partially depends on its rhizosphere-a dynamic zone governed by complex interactions between plant roots and a plethora of commensal, mutualistic, symbiotic, or pathogenic microbes that shape plant fitness. In an exploratory endeavor, we investigated the effects of a consortium consisting of ectomycorrhizal fungi and a beneficial Pseudomonas sp. strain GM41 on plant growth (including height, stem girth, leaf, and root growth) and as well as growth rate over time, across four Populus trichocarpa genotypes. Additionally, we compared the level of total organic carbon and plant exometabolite profiles across different poplar genotypes in the presence of the microbial consortium. These data revealed no significant difference in plant growth parameters between the treatments and the control across four different poplar genotypes at 7 weeks post-inoculation. However, total organic carbon and exometabolite profiles were significantly different between the genotypes and the treatments. These findings suggest that this microbial consortium has the potential to trigger early signaling responses in poplar, influencing its metabolism in ways crucial for later developmental processes and stress tolerance.PMID:38028650 | PMC:PMC10660807 | DOI:10.1002/pld3.544

Intestinal microbiota dysbiosis and liver metabolomic changes during brain death

Wed, 29/11/2023 - 12:00
J Intensive Med. 2023 May 10;3(4):345-351. doi: 10.1016/j.jointm.2023.02.006. eCollection 2023 Oct 31.ABSTRACTBACKGROUND: Whether a causative link exists between brain death (BD) and intestinal microbiota dysbiosis is unclear, and the distortion in liver metabolism associated with BD requires further exploration.METHODS: A rat model of BD was constructed and sustained for 9 h (BD group, n=6). The sham group (n=6) underwent the same procedures, but the catheter was inserted into the epidural space without ballooning. Intestinal contents and portal vein plasma were collected for microbiota sequencing and microbial metabolite detection. Liver tissue was resected to investigate metabolic alterations, and the results were compared with those of a sham group.RESULTS: α-diversity indexes showed that BD did not alter bacterial diversity. Microbiota dysbiosis occurred after 9 h of BD. At the family level, Peptostreptococcaceae and Bacteroidaceae were both decreased in the BD group. At the genus level, Romboutsia, Bacteroides, Erysipelotrichaceae_UCG_004, Faecalibacterium, and Barnesiella were enriched in the sham group, whereas Ruminococcaceae_UCG_007, Lachnospiraceae_ND3007_group, and Papillibacter were enriched in the BD group. Short-chain fatty acids, bile acids, and 132 other microbial metabolites remained unchanged in both the intestinal contents and portal vein plasma of the BD group. BD caused alterations in 65 metabolites in the liver, of which, carbohydrates, amino acids, and organic acids accounted for 64.6%. Additionally, 80.0% of the differential metabolites were decreased in the BD group livers. Galactose metabolism was the most significant metabolic pathway in the BD group.CONCLUSIONS: BD resulted in microbiota dysbiosis in rats; however, this dysbiosis did not alter microbial metabolites. Deterioration in liver metabolic function during extended periods of BD may reflect a continuous worsening in energy deficiency.PMID:38028643 | PMC:PMC10658038 | DOI:10.1016/j.jointm.2023.02.006

Integrative analysis of non-targeted metabolome and transcriptome reveals the mechanism of volatile formation in pepper fruit

Wed, 29/11/2023 - 12:00
Front Genet. 2023 Nov 10;14:1290492. doi: 10.3389/fgene.2023.1290492. eCollection 2023.ABSTRACTIntroduction: Aroma is a key inherent quality attributes of pepper fruit, yet the underlying mechanisms of aroma compound biosynthesis remain unclear. Methods: In this study, the volatile profile of the QH (cultivated Capsicum chinense) and WH (cultivated Capsicum annuum) pepper varieties were putatively identified during fruit development using gas chromatography-mass spectrometry (GC-MS). Results and discussion: The results identified 203 volatiles in pepper, and most of the esters, terpenes, aldehydes and alcohols were significantly down-regulated with fruit ripening. The comparison of volatile components between varieties revealed that aldehydes and alcohols were highly expressed in the WH fruit, while esters and terpenes with fruity or floral aroma were generally highly accumulated in the QH fruit, providing QH with a fruity odor. Transcriptome analysis demonstrated the close relationship between the synthesis of volatiles and the fatty acid and terpene metabolic pathways, and the high expression of the ADH, AAT and TPS genes was key in determining the accumulation of volatiles in pepper fruit. Furthermore, integrative metabolome and transcriptome analysis revealed that 208 differentially expressed genes were highly correlated with 114 volatiles, and the transcription factors of bHLH, MYB, ARF and IAA were identified as fundamental for the regulation of volatile synthesis in pepper fruit. Our results extend the understanding of the synthesis and accumulation of volatiles in pepper fruit.PMID:38028623 | PMC:PMC10667453 | DOI:10.3389/fgene.2023.1290492

Serum metabolomics identified specific lipid compounds which may serve as markers of disease progression in patients with Alström and Bardet-Biedl syndromes

Wed, 29/11/2023 - 12:00
Front Mol Biosci. 2023 Nov 6;10:1251905. doi: 10.3389/fmolb.2023.1251905. eCollection 2023.ABSTRACTObjectives: Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) are among the so-called ciliopathies and are associated with the development of multiple systemic abnormalities, including early childhood obesity and progressive neurodegeneration. Given the progressive deterioration of patients' quality of life, in the absence of defined causal treatment, it seems reasonable to identify the metabolic background of these diseases and search for their progression markers. The aim of this study was to find metabolites characteristic to ALMS and BBS, correlating with clinical course parameters, and related to the diseases progression. Methods: Untargeted metabolomics of serum samples obtained from ALMS and BBS patients (study group; n = 21) and obese/healthy participants (control group; each of 35 participants; n = 70) was performed using LC-QTOF-MS method at the study onset and after 4 years of follow-up. Results: Significant differences in such metabolites as valine, acylcarnitines, sphingomyelins, phosphatidylethanolamines, phosphatidylcholines, as well as lysophosphatidylethanolamines and lysophosphatidylcholines were observed when the study group was compared to both control groups. After a follow-up of the study group, mainly changes in the levels of lysophospholipids and phospholipids (including oxidized phospholipids) were noted. In addition, in case of ALMS/BBS patients, correlations were observed between selected phospholipids and glucose metabolism parameters. We also found correlations of several LPEs with patients' age (p < 0.05), but the level of only one of them (hexacosanoic acid) correlated negatively with age in the ALMS/BBS group, but positively in the other groups. Conclusion: Patients with ALMS/BBS have altered lipid metabolism compared to controls or obese subjects. As the disease progresses, they show elevated levels of lipid oxidation products, which may suggest increased oxidative stress. Selected lipid metabolites may be considered as potential markers of progression of ALMS and BBS syndromes.PMID:38028552 | PMC:PMC10657895 | DOI:10.3389/fmolb.2023.1251905

High-throughput quantitation of amino acids and acylcarnitine in cerebrospinal fluid: identification of PCNSL biomarkers and potential metabolic messengers

Wed, 29/11/2023 - 12:00
Front Mol Biosci. 2023 Oct 31;10:1257079. doi: 10.3389/fmolb.2023.1257079. eCollection 2023.ABSTRACTBackground: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin's lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL). Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling. Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients. Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.PMID:38028545 | PMC:PMC10644155 | DOI:10.3389/fmolb.2023.1257079

A one-year pilot study comparing direct-infusion high resolution mass spectrometry based untargeted metabolomics to targeted diagnostic screening for inherited metabolic diseases

Wed, 29/11/2023 - 12:00
Front Mol Biosci. 2023 Nov 2;10:1283083. doi: 10.3389/fmolb.2023.1283083. eCollection 2023.ABSTRACTBackground: Early diagnosis of inherited metabolic diseases (IMDs) is important because treatment may lead to reduced mortality and improved prognosis. Due to their diversity, it is a challenge to diagnose IMDs in time, effecting an emerging need for a comprehensive test to acquire an overview of metabolite status. Untargeted metabolomics has proven its clinical potential in diagnosing IMDs, but is not yet widely used in genetic metabolic laboratories. Methods: We assessed the potential role of plasma untargeted metabolomics in a clinical diagnostic setting by using direct infusion high resolution mass spectrometry (DI-HRMS) in parallel with traditional targeted metabolite assays. We compared quantitative data and qualitative performance of targeted versus untargeted metabolomics in patients suspected of an IMD (n = 793 samples) referred to our laboratory for 1 year. To compare results of both approaches, the untargeted data was limited to polar metabolites that were analyzed in targeted plasma assays. These include amino acid, (acyl)carnitine and creatine metabolites and are suitable for diagnosing IMDs across many of the disease groups described in the international classification of inherited metabolic disorders (ICIMD). Results: For the majority of metabolites, the concentrations as measured in targeted assays correlated strongly with the semi quantitative Z-scores determined with DI-HRMS. For 64/793 patients, targeted assays showed an abnormal metabolite profile possibly indicative of an IMD. In 55 of these patients, similar aberrations were found with DI-HRMS. The remaining 9 patients showed only marginally increased or decreased metabolite concentrations that, in retrospect, were most likely to be clinically irrelevant. Illustrating its potential, DI-HRMS detected additional patients with aberrant metabolites that were indicative of an IMD not detected by targeted plasma analysis, such as purine and pyrimidine disorders and a carnitine synthesis disorder. Conclusion: This one-year pilot study showed that DI-HRMS untargeted metabolomics can be used as a first-tier approach replacing targeted assays of amino acid, acylcarnitine and creatine metabolites with ample opportunities to expand. Using DI-HRMS untargeted metabolomics as a first-tier will open up possibilities to look for new biomarkers.PMID:38028537 | PMC:PMC10657655 | DOI:10.3389/fmolb.2023.1283083

Untargeted metabolomic and lipidomic analyses reveal lipid dysregulation in the plasma of acute leukemia patients

Wed, 29/11/2023 - 12:00
Front Mol Biosci. 2023 Nov 10;10:1235160. doi: 10.3389/fmolb.2023.1235160. eCollection 2023.ABSTRACTAcute leukemias (AL) are aggressive neoplasms with high mortality rates. Metabolomics and oxidative status have emerged as important tools to identify new biomarkers with clinical utility. To identify the metabolic differences between healthy individuals (HI) and patients with AL, a multiplatform untargeted metabolomic and lipidomic approach was conducted using liquid and gas chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS or GC-QTOF-MS). Additionally, the total antioxidant capacity (TAC) was measured. A total of 20 peripheral blood plasma samples were obtained from patients with AL and 18 samples from HI. Our analysis revealed 135 differentially altered metabolites in the patients belonging to 12 chemical classes; likewise, the metabolic pathways of glycerolipids and sphingolipids were the most affected in the patients. A decrease in the TAC of the patients with respect to the HI was evident. This study conducted with a cohort of Colombian patients is consistent with observations from other research studies that suggest dysregulation of lipid compounds. Furthermore, metabolic differences between patients and HI appear to be independent of lifestyle, race, or geographic location, providing valuable information for future advancements in understanding the disease and developing more global therapies.PMID:38028534 | PMC:PMC10667492 | DOI:10.3389/fmolb.2023.1235160

Clinical efficacy and metabolomic analysis of ozone major autohemotherapy for the treatment of herpes zoster

Wed, 29/11/2023 - 12:00
Postepy Dermatol Alergol. 2023 Oct;40(5):693-698. doi: 10.5114/ada.2023.130522. Epub 2023 Aug 22.ABSTRACTINTRODUCTION: It is essential to understand the underlying changes in the patients' metabolic profiles that may be indicative of the therapy's effectiveness.AIM: To prospectively analyse the clinical efficacy of ozone autohemotherapy in the treatment of acute herpes zoster and investigate its impact on serum metabolomics.MATERIAL AND METHODS: A total of 76 patients with acute herpes zoster between May 2018 and June 2020 were enrolled and divided into an experimental group and a control group. The pain location, Numeric Rating Scale (NRS) scores before and after treatment (1 week, 1 month, 3 months, and 6 months post-treatment), medication usage, and Quality of Sleep (QS) scores were prospectively analysed. Additionally, serum metabolomic data were obtained and analysed before and 6 months after the treatment.RESULTS: There were statistically significant differences in the total NRS scores before and after ozone autohemotherapy (p < 0.05). The NRS scores of both groups significantly decreased (p < 0.05). At the 6-month follow-up, no patients were lost, and 83 patients completed the follow-up. The NRS improvement at 1 week, 1 month, 3 months, and 6 months post-treatment in the experimental group was significantly lower than that in the control group (p < 0.05). There was no significant difference in the medication usage (pregabalin or tramadol sustained-release tablets) between the two groups (p > 0.05). One month after treatment, the QS score improvement in the diabetes group was significantly lower than that in the non-diabetes group (p < 0.05). Serum metabolomics analysis revealed three significantly decreased metabolites, namely creatine, adipate, and glucose, after treatment.CONCLUSIONS: Ozone autohemotherapy is an effective treatment for acute herpes zoster patients and can rapidly and effectively alleviate pain symptoms in the short term. The changes in serum metabolomics may provide further insights into the treatment mechanism.PMID:38028414 | PMC:PMC10646704 | DOI:10.5114/ada.2023.130522

Effect of IFN‑γ encapsulated liposomes on major signal transduction pathways in the lymphocytes of patients with lung cancer

Wed, 29/11/2023 - 12:00
Oncol Lett. 2023 Nov 8;27(1):8. doi: 10.3892/ol.2023.14141. eCollection 2024 Jan.ABSTRACTGlobally, lung cancer affected 2.2 million individuals and caused 1.8 million deaths in 2021. Lung cancer is caused by smoking, genetics and other factors. IFN-γ has anticancer activity. However, the mechanism by which IFN-γ has an effect on lung cancer is not fully understood. The present study aimed to assess the effect of IFN-γ on the peripheral lymphocytes of patients with lung cancer compared with healthy controls. The efficacy of IFN-γ against oxidative stress was assessed using a comet repair assay and the effects of IFN-γ on p53, PARP1 and OGG1 genes and protein levels in lymphocytes was evaluated by RT-qPCR and western blotting. DNA damage was significantly reduced in the lymphocytes of patients treated with IFN-γ. However, there was no effect in the cells of healthy individuals after treatment with naked IFN-γ [IFN-γ (N)] and liposomal IFN-γ [IFN-γ (L)]. Following treatment with IFN-γ (N) and IFN-γ (L), the p53, PARP1 and OGG1 protein and gene expression levels were significantly increased (P<0.001). It has been suggested that IFN-γ may induce p53-mediated cell cycle arrest and DNA repair in patients. These findings supported the idea that IFN-γ (N) and IFN-γ (L) may serve a significant role in the treatment of lung cancer, via cell cycle arrest of cancer cells and repair mechanisms.PMID:38028180 | PMC:PMC10664063 | DOI:10.3892/ol.2023.14141

Metabolomics as a tool for geographic origin assessment of roasted and green coffee beans

Wed, 29/11/2023 - 12:00
Heliyon. 2023 Oct 30;9(11):e21402. doi: 10.1016/j.heliyon.2023.e21402. eCollection 2023 Nov.ABSTRACTCoffee is widely consumed across the globe. The most sought out varieties are Arabica and Robusta which differ significantly in their aroma and taste. Furthermore, varieties cultivated in different regions are perceived to have distinct characteristics encouraging some producers to adopt the denomination of origin label. These differences arise from variations on metabolite content related to edaphoclimatic conditions and post-harvest management among other factors. Although sensory analysis is still standard for coffee brews, instrumental analysis of the roasted and green beans to assess the quality of the final product has been encouraged. Metabolomic profiling has risen as a promising approach not only for quality purposes but also for geographic origin assignment. Many techniques can be applied for sample analysis: chromatography, mass spectrometry, and NMR have been explored. The data collected is further sorted by multivariate analysis to identify similar characteristics among the samples, reduce dimensionality and/or even propose a model for predictive purposes. This review focuses on the evolution of metabolomic profiling for the geographic origin assessment of roasted and green coffee beans in the last 21 years, the techniques that are usually applied for sample analysis and also the most common approaches for the multivariate analysis of the collected data. The prospect of applying a wide range of analytical techniques is becoming an unbiased approach to determine the origin of different roasted and green coffee beans samples with great correlation. Predictive models worked accurately for the geographic assignment of unknown samples once the variety was known.PMID:38028010 | PMC:PMC10651463 | DOI:10.1016/j.heliyon.2023.e21402

Effects of soda water on blood lipid and metabolic profiling of urine in hyperlipidemia rats using UPLC/Triple-TOF MS

Wed, 29/11/2023 - 12:00
Heliyon. 2023 Oct 28;9(11):e21666. doi: 10.1016/j.heliyon.2023.e21666. eCollection 2023 Nov.ABSTRACTThe effects of a natural soda water (Shi Han Quan, SHQ) on hyperlipidemia and the changes of urine metabolic profiling by metabolomics techniques were investigate. Thirty six Wistar rats weighing 160-200 g were divided into control group, hyperlipidemia (HL) group, and hyperlipidemia + SHQ water (SHQ) group. The metabolites in urine were determined using ultra high performance liquid chromatography-triple-time of flight-mass spectrometry (UPLC/Triple-TOF MS). At the end of 1 month and 3 months, the total glyceride (TG) level was significantly lower in SHQ group compared to HL group. There was no significantly difference in total cholesterol (TC) levels in HL group compared with SHQ group. The results showed that dinking SHQ water can improve the TG, but with no effects on TC. After drinking SHQ water for 3 months, the rats in different groups could be classified into different clusters according to the metabolites in urine. Total 15 important metabolites were found and correlated with disturbance of amino acid, phospholipid, fatty acid and vitamin metabolism, which suggested the changes of metabolism in the body and possible mechanism by which SHQ improved the TG. These findings provide a new insight for the prevention and control of hyperlipidemia.PMID:38027945 | PMC:PMC10643294 | DOI:10.1016/j.heliyon.2023.e21666

Demaghi, a polyherbal formulation, mitigates aluminum chloride-induced neurological impairment in mice: Insights from phytochemical analysis and behavioral assessment

Wed, 29/11/2023 - 12:00
Heliyon. 2023 Oct 27;9(11):e21234. doi: 10.1016/j.heliyon.2023.e21234. eCollection 2023 Nov.ABSTRACTHerbal products have been very popular in Pakistan for their curative significance against various disorders. Demaghi (DEMG) is a widely used herbal product claimed to own natural substances having neuroprotective potential. The current study aims to scientifically validate the chemical composition as well as its neuroprotective claims of this widely used herbal tonic. The commercially available Demaghi product was chemically characterized for its phytocomposition. The mice were treated with two doses of Demaghi (DEMG 50 mg and 100 mg/kg/day), and the effects of its prolonged exposure on animal anxiety, memory, and depression were noted through a series of behavioral tests in the AlCl3-induced memory deficient mice model. Besides that, dissected brains were biochemically analyzed for oxidative stress markers and acetylcholinesterase activity, as well as histopathological changes. The study outcomes showed that DEMG (100 mg/kg/day) has prominent anti-anxiety effects, memory-enhancing properties, and anti-depressants effects observed in the AlCl3-induced memory-deficient mice model. Biochemical assays also showed a greater decrease in oxidative stress of tested animals treated with 100 mg/kg/day of DEMG. The histopathological analysis also revealed that administration of DEMG reduced the AlCl3-induced toxicity. UPLC-MS results revealed the presence of many phytoconstituents, which showed to support cholinergic signaling in in-silico studies. The current research validates the neurological benefits of Demaghi for memory-boosting properties. The phytocompounds present in Demaghi exert neuroprotective effects, possibly by enhancing the cholinergic neurotransmission and combating the neurotoxin-induced oxidative stress.PMID:38027790 | PMC:PMC10643107 | DOI:10.1016/j.heliyon.2023.e21234

Circulating choline and phosphocholine measurement by a hydrophilic interaction liquid chromatography-tandem mass spectrometry

Wed, 29/11/2023 - 12:00
Heliyon. 2023 Nov 2;9(11):e21921. doi: 10.1016/j.heliyon.2023.e21921. eCollection 2023 Nov.ABSTRACTBACKGROUND: Given the growing interest in studying the role of choline and phosphocholine in the development and progression of tumor pathology, in this study we describe the development and validation of a fast and robust method for the simultaneous analysis of choline and phosphocholine in human plasma.METHODS: Choline and phosphocholine quantification in human plasma was obtained using a hydrophilic interaction liquid chromatography-tandem mass spectrometry technique. Assay performance parameters were evaluated using EMA guidelines.RESULTS: Calibration curve ranged from 0.60 to 38.40 μmol/L (R2 = 0.999) and 0.08-5.43 μmol/L (R2 = 0.998) for choline and phosphocholine, respectively. The Limit Of Detection of the method was 0.06 μmol/L for choline and 0.04 μmol/L for phosphocholine. The coefficient of variation range for intra-assay precision is 2.2-4.1 % (choline) and 3.2-15 % (phosphocholine), and the inter-assay precision range is < 1-6.5 % (choline) and 6.2-20 % (phosphocholine). The accuracy of the method was below the ±20 % benchmarks at all the metabolites concentration levels. In-house plasma pool of apparently healthy adults was tested, and a mean concentration of 15.97 μmol/L for Choline and 0.34 μmol/L for Phosphocholine was quantified.CONCLUSIONS: The developed method shows good reliability in quantifying Choline and Phosphocholine in human plasma for clinical purposes.PMID:38027764 | PMC:PMC10665723 | DOI:10.1016/j.heliyon.2023.e21921

The neuroprotective potential of turmeric rhizome and bitter melon on aspartame-induced spatial memory impairment in rats

Wed, 29/11/2023 - 12:00
Heliyon. 2023 Nov 3;9(11):e21693. doi: 10.1016/j.heliyon.2023.e21693. eCollection 2023 Nov.ABSTRACTAspartame is widely used artificial sweetener. However, chronic exposure to aspartame led to spatial memory impairment and elevated oxidative stress in the brain. Extract of turmeric rhizome (Curcuma longa) (TUR) and extract of bitter melon (Momordica charantia) (BM) is known to have antioxidant activity. The present study was aimed to examine the neuroprotective potential of TUR and BM extracts, either as single or as combination, against the effects of aspartame in the brain. Here, Sprague-Dawley rats fed with aspartame (40 mg/kg BW) for 28 days were compared with rats fed with extract and aspartame. To assess neuroprotective potential, rats were given extract 7 days before and during aspartame treatment. Spatial memory was assessed with Morris water maze test followed with H&E staining of hippocampal region. Brain lipid peroxidation and enzymatic activity of malondialdehyde (MDA), glutathione peroxidase (GPx), and Acetylcholinesterase (AChE) were measured to probe status of oxidative stress in the brain. Aspartame-treated rats demonstrated spatial memory impairment and reduced number of hippocampal cells and elevated levels of MDA, downregulated activity of GPx and elevated activity of AChE. In contrast, animals received both aspartame and extract demonstrated better spatial memory function, higher number of hippocampal areas, increased GPX activity, reduced MDA levels, and decreased AChE activity were observed in the brain of extract-treated rats. Taken together, our results suggest that extract of TUR rhizome and BM fruit exhibit antioxidant activity which may contribute to the neuroprotective effects against aspartame-induced memory impairment in rats.PMID:38027700 | PMC:PMC10665738 | DOI:10.1016/j.heliyon.2023.e21693

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