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

Characteristics of the gut microbiome in esports players compared with those in physical education students and professional athletes

Thu, 02/02/2023 - 12:00
Front Nutr. 2023 Jan 16;9:1092846. doi: 10.3389/fnut.2022.1092846. eCollection 2022.ABSTRACTINTRODUCTION: Esports is a category of competitive video games that, in many aspects, may be similar to traditional sports; however, the gut microbiota composition of players has not been yet studied.MATERIALS AND METHODS: Here, we investigated the composition and function of the gut microbiota, as well as short chain fatty acids (SCFAs), and amino acids, in a group of 109 well-characterized Polish male esports players. The results were compared with two reference groups: 25 endurance athletes and 36 healthy students of physical education. DNA and metabolites isolated from fecal samples were analyzed using shotgun metagenomic sequencing and mass spectrometry, respectively. Physical activity and nutritional measures were evaluated by questionnaire.RESULTS: Although anthropometric, physical activity and nutritional measures differentiated esports players from students, there were no differences in bacterial diversity, the Bacteroidetes/Firmicutes ratio, the composition of enterotype clusters, metagenome functional content, or SCFA concentrations. However, there were significant differences between esports players and students with respect to nine bacterial species and nine amino acids. By contrast, all of the above-mentioned measures differentiated professional athletes from esports players and students, with 45 bacteria differentiating professional athletes from the former and 31 from the latter. The only species differentiating all three experimental groups was Parabacteroides distasonis, showing the lowest and highest abundance in esports players and athletes, respectively.CONCLUSION: Our study confirms the marked impact of intense exercise training on gut microbial structure and function. Differences in lifestyle and dietary habits between esports players and physical education students appear to not have a major effect on the gut microbiota.PMID:36726816 | PMC:PMC9884692 | DOI:10.3389/fnut.2022.1092846

Protection effect of gut microbiota composition and acetate absorption against hypertension-induced damages on the longevity population in Guangxi, China

Thu, 02/02/2023 - 12:00
Front Nutr. 2023 Jan 16;9:1070223. doi: 10.3389/fnut.2022.1070223. eCollection 2022.ABSTRACTINTRODUCTION: Recent evidence supports a role for the gut microbe-metabolites in longevity. However, the phenomenon of hypertension is more common in the longevity area and whether hypertension is associated with longevity remains unclear. Here, we hypothesize that the levels of gut microbiota, SCFAs, and urine metabolites were different between hypertension elderly and hypertension longevity.METHODS: We recruited 46 elderly volunteers from Donglan County, Guangxi, and 32 were selected and included in the experiment. The subjects with hypertension were divided into two groups according to age, Hypertension Elderly (HTE, aged 70.5 ± 8.59, n = 19) and Hypertension Longevity (HTL, aged 100 ± 5.72, n = 13). The gut microbiota, SCFAs, and urine metabolites were determined by three-generation 16S rRNA full-length sequencing, GC-MS, and 1H-NMR, respectively.RESULTS: Compared with the HTL group, the HTE group had higher levels of hypertension-related genera Klebsiella and Streptococcus, while having lower levels of the SCFA-producing genera Bacteroides, Faecalibacterium, and Alistipes. Based on LEFse analysis, Klebsiella pneumoniae, Lactobacillus gasseri, Streptococcus salivarius, Ruminococcus, Actinomyces, Rikenellaceae, f_Saccharimonadaceae, Clostridium perfringens, and Bacteroids, Faecalibacterium prausnitzii, Parabacteroides, Alistipes were biomarkers that showed significant differences between the groups. In addition, the microbial pathways associated with K. pneumoniae and E. coli may promote hypertension, while A. muciniphila may play a role in reversing the development of hypertension in long-lived elderly. Metabolomics revealed that HTL contained a lower concentration of fecal acetate and propionate than HTE, while it contained a higher concentration of serum acetate and urine acetate. Furthermore, their immune cells exhibited no significant changes in SCFAs receptors.CONCLUSION: Although long-lived elderly have extremely high systolic blood pressure, their unique gut microbiota composition and efficient acetate absorption in the colon may offset the damages caused by hypertension and maintain healthy homeostasis.PMID:36726815 | PMC:PMC9884688 | DOI:10.3389/fnut.2022.1070223

Metabolomic fingerprinting based on network analysis of volatile aroma compounds during the forced aging of Huangjiu: Effects of dissolved oxygen and temperature

Thu, 02/02/2023 - 12:00
Front Nutr. 2023 Jan 16;10:1114880. doi: 10.3389/fnut.2023.1114880. eCollection 2023.ABSTRACTINTRODUCTION: Huangjiu is an important Chinese alcoholic beverage, usually prepared from rice. Although its unique flavor improves with prolonged storage in traditional pottery jars, knowledge of the aging mechanism, necessary for commercialization of an optimum product, remains unclear.METHODS: Here, volatile aroma compounds from forced aged samples exposed to different temperatures and oxygen treatments were measured by GC/MS. After retention time alignment and normalization, the peak vectors were compared over storage time using Pearson's correlation, and a correlation network was established. Marker compounds, representative of traditionally aged Huangjiu, were then monitored and compared to similar compounds in the forced aged product.RESULTS AND DISCUSSION: Correlation network analysis revealed the following: Temperature had little effect on most aroma compounds; alcohols, acids, and esters all increased with increasing dissolved oxygen, while polyphenols, lactones, and ketones were readily oxidized; aldehydes (e.g., furfural and benzaldehyde) were highly dependent on both temperature and dissolved oxygen. Dynamic changes in the targeted aging-markers showed that a higher initial oxygen concentration intensified the "aging-aroma" of Huangjiu in the early and middle stages of storage. Consequently, careful control of oxygen supplementation and storage temperature could be beneficial in controlling the desirable flavor of Huangjiu in the artificially aged product.PMID:36726696 | PMC:PMC9884831 | DOI:10.3389/fnut.2023.1114880

Downregulation of barley ferulate 5-hydroxylase dramatically alters straw lignin structure without impact on mechanical properties

Thu, 02/02/2023 - 12:00
Front Plant Sci. 2023 Jan 16;13:1125003. doi: 10.3389/fpls.2022.1125003. eCollection 2022.ABSTRACTBarley is a major cereal crop for temperate climates, and a diploid genetic model for polyploid wheat. Cereal straw biomass is an attractive source of feedstock for green technologies but lignin, a key determinant of feedstock recalcitrance, complicates bio-conversion processes. However, manipulating lignin content to improve the conversion process could negatively affect agronomic traits. An alternative approach is to manipulate lignin composition which influences the physical and chemical properties of straw. This study validates the function of a barley ferulate 5-hydroxylase gene and demonstrates that its downregulation using the RNA-interference approach substantially impacts lignin composition. We identified five barley genes having putative ferulate 5-hydroxylase activity. Downregulation of HvF5H1 substantially reduced the lignin syringyl/guaiacyl (S/G) ratio in straw while the lignin content, straw mechanical properties, plant growth habit, and grain characteristics all remained unaffected. Metabolic profiling revealed significant changes in the abundance of 173 features in the HvF5H1-RNAi lines. The drastic changes in the lignin polymer of transgenic lines highlight the plasticity of barley lignification processes and the associated potential for manipulating and improving lignocellulosic biomass as a feedstock for green technologies. On the other hand, our results highlight some differences between the lignin biosynthetic pathway in barley, a temperate climate grass, and the warm climate grass, rice, and underscore potential diversity in the lignin biosynthetic pathways in grasses.PMID:36726680 | PMC:PMC9886061 | DOI:10.3389/fpls.2022.1125003

The differential modulation of secondary metabolism induced by a protein hydrolysate and a seaweed extract in tomato plants under salinity

Thu, 02/02/2023 - 12:00
Front Plant Sci. 2023 Jan 16;13:1072782. doi: 10.3389/fpls.2022.1072782. eCollection 2022.ABSTRACTClimate change and abiotic stress challenges in crops are threatening world food production. Among others, salinity affects the agricultural sector by significantly impacting yield losses. Plant biostimulants have received increasing attention in the agricultural industry due to their ability to improve health and resilience in crops. The main driving force of these products lies in their ability to modulate plant metabolic processes involved in the stress response. This study's purpose was to investigate the effect of two biostimulant products, including a protein hydrolysate (Clever HX®) and a seaweed extract with high amino acids content (Ascovip®), and their combination, on the metabolomics profile of tomato crops grown under salt stress (150 mM NaCl). Several stress indicators (leaf relative water content, membrane stability index, and photosynthesis activity) and leaf mineral composition after salinity stress exposure were assessed to evaluate stress mitigation, together with growth parameters (shoot and root biomasses). After that, an untargeted metabolomics approach was used to investigate the mechanism of action of the biostimulants and their link with the increased resilience to stress. The application of the biostimulants used reduced the detrimental effect of salinity. In saline conditions, protein hydrolysate improved shoot dry weight while seaweed extracts improved root dry weight. Regarding stress indicators, the application of the protein hydrolysate was found to alleviate the membrane damage caused by salinity stress compared to untreated plants. Surprisingly, photosynthetic activity significantly improved after treatment with seaweed extracts, suggesting a close correlation between root development, root water assimilation capacity and photosynthetic activity. Considering the metabolic reprogramming after plant biostimulants application, protein hydrolysates and their combination with seaweed extracts reported a distinctive metabolic profile modulation, mainly in secondary metabolite, lipids and fatty acids, and phytohormones biosynthetic pathways. However, treatment with seaweed extract reported a similar metabolic reprogramming trend compared to salinity stress. Our findings indicate a different mechanism of action modulated by protein hydrolysate and seaweed extract, suggesting stronger activity as a stress mitigator of protein hydrolysate in tomato crops under salinity stress.PMID:36726679 | PMC:PMC9884811 | DOI:10.3389/fpls.2022.1072782

Effect of different regions on fermentation profiles, microbial communities, and their metabolomic pathways and properties in Italian ryegrass silage

Thu, 02/02/2023 - 12:00
Front Microbiol. 2023 Jan 16;13:1076499. doi: 10.3389/fmicb.2022.1076499. eCollection 2022.ABSTRACTINTRODUCTION: Italian ryegrass is less studied in northern China due to high-quality forage grass has not been fully utilized. Full utilization of high-quality forage grass helps to alleviate the shortage of forage grass in winter and spring season and guarantee stable development of livestock production. Consequently, this study was aimed to evaluate the effects of different regions in northern China on the fermentative products, bacterial community compositions, and metabolic pathways and metabolites of Italian ryegrass silage.METHODS: The Italian ryegrass was harvested from three regions (Ordos-WK; Hohhot-AK; Ulanqab-SYK) and ensiled for 60 days. Single molecule real-time (SMRT) sequencing and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) were used to analyze bacterial communities and metabolites, respectively.RESULTS: After 60 d of fermentation, the SYK group had the lowest pH (4.67), the highest lactic acid contents (95.02 g/kg DM) and largest lactic acid bacteria populations (6.66 log10 cfu/g FM) among the treatment groups. In addition, the SYK group had the highest abundance of Lactiplantibacillus plantarum (63.98%). In SYK group, isoquinoline alkaloid biosynthesis was the significantly enriched (p < 0.05) and high-impact value (0.0225) metabolic pathway. In AK group, tryptophan metabolism the was the significantly enriched (p < 0.001) and high-impact value (0.1387) metabolic pathway. In WK group, citrate cycle (TCA cycle) was the significantly enriched (p < 0.001) and high-impact value (0.1174) metabolic pathway. Further, Lactiplantibacillus plantarum was positively correlated with cinnamic acid, tetranor 12-HETE, D-Mannitol, (2S)-2-amino-4-methylpentanoic acid L-Leucine, guanine, isoleucyl-aspartate and 3,4-Dihydroxyphenyl propanoate, but negatively correlated with isocitrate and D-mannose.DISCUSSION: In conclusion, this study can improve our understanding of the ensiling microbiology and metabolomics in different regions to further regulate the fermentation products and promote livestock production.PMID:36726558 | PMC:PMC9885166 | DOI:10.3389/fmicb.2022.1076499

Characterization of the Microbiome and Host's Metabolites of the Lower Respiratory Tract During Acute Community-Acquired Pneumonia Identifies Potential Novel Markers

Thu, 02/02/2023 - 12:00
Infect Drug Resist. 2023 Jan 26;16:581-594. doi: 10.2147/IDR.S394779. eCollection 2023.ABSTRACTPURPOSE: Community-acquired pneumonia (CAP) is one of the most frequently encountered infectious diseases worldwide. Few studies have explored the microbial composition of the lower respiratory tract (LRT) and host metabolites of CAP. We analyzed the microbial composition of the LRT and levels of host metabolites to explore new biomarkers for CAP.PATIENTS AND METHODS: Bronchoalveolar lavage fluid (BALF) was collected from 28 CAP patients and 20 healthy individuals. Following centrifugation, BALF pellets were used for amplicon sequencing of a variable region of the bacterial 16S rDNA gene to characterize the microbial composition. Non-targeted metabolomics was used to detect host's metabolites in the supernatant.RESULTS: Compared with healthy individuals, the bacterial alpha diversity in the LRT of CAP patients was significantly lower in CAP patients (p<0.05). On the bacterial genus level, over 20 genera were detected with lower relative abundance (p<0.05), while the relative abundance of Ruminiclostridium-6 was significantly higher in CAP patients. The levels of the host metabolites dimethyldisulfide, choline, pyrimidine, oleic acid and N-acetyl-neuraminic acid were all increased in BALF of CAP patients (p<0.05), while concentrations of lysophosphatidylcholines (LPC (12:0/0:0)) and phosphatidic acid (PA (20:4/2:0)) were decreased (p<0.05). Furthermore, the relative abundance of Parvimonas, Treponema-2, Moraxella, Aggregatibacter, Filifactor, Fusobacterium, Lautropia and Neisseria negatively correlated with concentrations of oleic acid (p<0.05). A negative correlation between the relative abundance of Treponema-2, Moraxella, Filifactor, Fusobacterium and dimethyldisulfide concentrations was also observed (p<0.05). In contrast, the relative abundance of Treponema-2, Moraxella, Filifactor, and Fusobacterium was found to be positively associated with concentrations of LPC (12:0/0:0) and PA (20:4/2:0) (p<0.05).CONCLUSION: The composition of the LRT microbiome differed between healthy individuals and CAP patients. We propose that some respiratory microbial components and host metabolites are potentially novel diagnostic markers of CAP.PMID:36726385 | PMC:PMC9885967 | DOI:10.2147/IDR.S394779

Effect of olive by-products feed supplementation on physicochemical and microbiological profile of Provola cheese

Thu, 02/02/2023 - 12:00
Front Microbiol. 2023 Jan 16;14:1112328. doi: 10.3389/fmicb.2023.1112328. eCollection 2023.ABSTRACTINTRODUCTION: With the purpose to evaluate the effects of dietary olive cake, a source of bioactive phenolic compounds, as feed supplementation of lactating dairy cows on fatty acid composition, volatile organic compounds, and microbiological profiles of Provola cheese, we performed a two-arm study where control and experimental administered cows derived dairy have been compared.METHODS: Our panel of analyses include metabolomics, physicochemical detected variables, culture dependent and independent analyses, and a stringent statistical approach aimful at disclosing only statistically significant results.RESULTS AND DISCUSSION: Looking at the physicochemical variable's profiles, a higher content of unsaturated fatty acids, polyunsaturated fatty acid, and conjugated linoleic acids as well of proteins were observed in experimental cheese samples, indicating the beneficial effect of dietary supplementation. Furthermore, based on volatilome composition, a clear cluster separation between control and experimental cheeses was obtained, mainly related to terpenes degradation, able of influencing their aroma and taste. Microbiological results showed a decrease of some spoilage related microbial groups in experimental cheeses, probably due to the inhibitory effect exerted by polyphenols compounds, that contrarily did not affect the core taxa of all cheese samples. This paper confirmed the promising utilization of olive by-product in farming practices to obtain more sustainable and safe dairy food products with lower environmental impact, mainly in Sicily and Mediterranean area, where waste disposal poses serious environmental and economic problems.PMID:36726372 | PMC:PMC9885796 | DOI:10.3389/fmicb.2023.1112328

Effect of PFOA exposure on diminished ovarian reserve and its metabolism

Thu, 02/02/2023 - 12:00
Reprod Biol Endocrinol. 2023 Feb 1;21(1):16. doi: 10.1186/s12958-023-01056-y.ABSTRACTOwing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.PMID:36726108 | DOI:10.1186/s12958-023-01056-y

Green manure increases peanut production by shaping the rhizosphere bacterial community and regulating soil metabolites under continuous peanut production systems

Thu, 02/02/2023 - 12:00
BMC Plant Biol. 2023 Feb 1;23(1):69. doi: 10.1186/s12870-023-04079-0.ABSTRACTBACKGROUND: Green manure (GM) is a crop commonly grown during fallow periods, which has been applied in agriculture as a strategy to regulate nutrient cycling, improve organic matter, and enhance soil microbial biodiversity, but to date, few studies have examined the effects of GM treatments on rhizosphere soil bacterial community and soil metabolites from continuous cropping peanut field.RESULTS: In this study, we found that the abundances of several functionally significant bacterial groups containing Actinobacteria, Acidobacteria, and genus Sphingomonas, which are associated with nitrogen cycling, were dramatically increased in GM-applied soils. Consistent with the bacterial community results, metabolomics analysis revealed a strong perturbation of nitrogen- or carbon-related metabolisms in GM-applied soils. The substantially up-regulated beneficial metabolites including sucrose, adenine, lysophosphatidylcholine (LPC), malic acid, and betaines in GM-applied soils may contribute to overcome continuous cropping obstacle. In contrast to peanut continuous cropping, planting winter wheat and oilseed rape in winter fallow period under continuous spring peanut production systems evidently improved the soil quality, concomitantly with raised peanut pod yield by 32.93% and 25.20%, in the 2020 season, respectively.CONCLUSIONS: GMs application is an effective strategy to overcome continuous cropping obstacle under continuous peanut production systems by improving nutrient cycling, soil metabolites, and rhizobacterial properties.PMID:36726076 | DOI:10.1186/s12870-023-04079-0

Effects of medwakh smoking on salivary metabolomics and its association with altered oral redox homeostasis among youth

Wed, 01/02/2023 - 12:00
Sci Rep. 2023 Feb 1;13(1):1870. doi: 10.1038/s41598-023-27958-w.ABSTRACTThe use of alternative tobacco products, particularly medwakh, has expanded among youth in the Middle East and around the world. The present study is conducted to investigate the biochemical and pathophysiological changes caused by medwakh smoking, and to examine the salivary metabolomics profile of medwakh smokers. Saliva samples were collected from 30 non-smokers and 30 medwakh smokers and subjected to metabolomic analysis by UHPLC-ESI-QTOF-MS. The CRP and Glutathione Peroxidase 1 activity levels in the study samples were quantified by ELISA and the total antioxidant capacity (TAC) by TAC assay kits. Statistical measurements and thorough validation of data obtained from untargeted metabolomics identified 37 uniquely and differentially abundant metabolites in saliva of medwakh smokers. The levels of phthalate, L-sorbose, cytosine, uridine, alpha-hydroxy hippurate, and L-nicotine were noticeably high in medwakh smokers. Likewise, 20 metabolic pathways were differentially altered in medwakh smokers. This study identified a distinctive saliva metabolomics profile in medwakh smokers associated with altered redox homeostasis, metabolic pathways, antioxidant system, and CRP levels. The impact of the altered metabolites in medwakh smokers and their diagnostic utility require further research in large cohorts.PMID:36725974 | DOI:10.1038/s41598-023-27958-w

A Perspective on Bone Morphogenetic Proteins: Dilemma behind Cancer-related Responses

Wed, 01/02/2023 - 12:00
Curr Drug Targets. 2023 Feb 1. doi: 10.2174/1389450124666230201144605. Online ahead of print.ABSTRACTBone morphogenetic proteins are a center of serious concern and are known to execute various cancer-related issues. The BMP signaling cascades have become more unpredictable as a result of their pleiotropic and risky characteristics, particularly when it comes to cancer responses. This perspective discusses the current therapeutic implications, emphasizes different cellular aspects that impact the failures of the current drug treatments, and speculates on future research avenues that include novel strategies like metabolomic studies and bio-mimetic peptide therapeutics to mitigate cancerous outcomes.PMID:36725830 | DOI:10.2174/1389450124666230201144605

Linking lifestyle factors to cardiovascular risk through metabolomics: Insights from a large population of diabetic patients followed-up for 11 years

Wed, 01/02/2023 - 12:00
Atherosclerosis. 2023 Jan 21:S0021-9150(23)00024-2. doi: 10.1016/j.atherosclerosis.2023.01.012. Online ahead of print.NO ABSTRACTPMID:36725416 | DOI:10.1016/j.atherosclerosis.2023.01.012

In silico method to maximise the biological potential of understudied metabolomic biomarkers: a study in pre-eclampsia

Wed, 01/02/2023 - 12:00
Gut. 2023 Feb 1:gutjnl-2022-329312. doi: 10.1136/gutjnl-2022-329312. Online ahead of print.NO ABSTRACTPMID:36725314 | DOI:10.1136/gutjnl-2022-329312

Correlation between intestinal and respiratory flora and their metabolites in a rat pneumoconiosis model

Wed, 01/02/2023 - 12:00
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2023 Jan 20;41(1):21-30. doi: 10.3760/cma.j.cn121094-20211011-00495.ABSTRACTObjective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.PMID:36725290 | DOI:10.3760/cma.j.cn121094-20211011-00495

Effect of Uremic Clearance Granules on improvement of chronic kidney disease in rats based on microbiome-metabolomics and its mechanism

Wed, 01/02/2023 - 12:00
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):160-169. doi: 10.19540/j.cnki.cjcmm.20220901.401.ABSTRACTThis research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.PMID:36725268 | DOI:10.19540/j.cnki.cjcmm.20220901.401

Anti-hyperuricemia activity and its mechanism of flavonoid extract from saffron floral bio-residues

Wed, 01/02/2023 - 12:00
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):148-159. doi: 10.19540/j.cnki.cjcmm.20220928.401.ABSTRACTA hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.PMID:36725267 | DOI:10.19540/j.cnki.cjcmm.20220928.401

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model

Wed, 01/02/2023 - 12:00
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):140-147. doi: 10.19540/j.cnki.cjcmm.20220914.401.ABSTRACTThis study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.PMID:36725266 | DOI:10.19540/j.cnki.cjcmm.20220914.401

Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness

Wed, 01/02/2023 - 12:00
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):82-95. doi: 10.19540/j.cnki.cjcmm.20220712.301.ABSTRACTWith the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.PMID:36725261 | DOI:10.19540/j.cnki.cjcmm.20220712.301

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology

Wed, 01/02/2023 - 12:00
Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(2):507-516. doi: 10.19540/j.cnki.cjcmm.20220913.702.ABSTRACTIn this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.PMID:36725240 | DOI:10.19540/j.cnki.cjcmm.20220913.702

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