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

Plasma Metabolite Profiling in the Search for Early-Stage Biomarkers for Lung Cancer: Some Important Breakthroughs

Sat, 11/05/2024 - 12:00
Int J Mol Sci. 2024 Apr 25;25(9):4690. doi: 10.3390/ijms25094690.ABSTRACTLung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster, and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already been shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterized by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation to their metabolic pathways and in light of the altered cancer metabolism.PMID:38731909 | DOI:10.3390/ijms25094690

Deciphering the Impact of Defecation Frequency on Gut Microbiome Composition and Diversity

Sat, 11/05/2024 - 12:00
Int J Mol Sci. 2024 Apr 25;25(9):4657. doi: 10.3390/ijms25094657.ABSTRACTThis study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1-3 times/week, n = 4), mid-frequent (4-6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S rRNA gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The Ruminococcus genus was predominant in the infrequent group, but decreased with more frequent defecation, while the Bacteroides genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.PMID:38731876 | DOI:10.3390/ijms25094657

Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer-A Model Study on Azoxymethane-Treated Rats

Sat, 11/05/2024 - 12:00
Int J Mol Sci. 2024 Apr 24;25(9):4635. doi: 10.3390/ijms25094635.ABSTRACTFactors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.PMID:38731854 | DOI:10.3390/ijms25094635

Host-Microbiome Crosstalk in Chronic Wound Healing

Sat, 11/05/2024 - 12:00
Int J Mol Sci. 2024 Apr 24;25(9):4629. doi: 10.3390/ijms25094629.ABSTRACTThe pathogenesis of chronic wounds (CW) involves a multifaceted interplay of biochemical, immunological, hematological, and microbiological interactions. Biofilm development is a significant virulence trait which enhances microbial survival and pathogenicity and has various implications on the development and management of CW. Biofilms induce a prolonged suboptimal inflammation in the wound microenvironment, associated with delayed healing. The composition of wound fluid (WF) adds more complexity to the subject, with proven pro-inflammatory properties and an intricate crosstalk among cytokines, chemokines, microRNAs, proteases, growth factors, and ECM components. One approach to achieve information on the mechanisms of disease progression and therapeutic response is the use of multiple high-throughput 'OMIC' modalities (genomic, proteomic, lipidomic, metabolomic assays), facilitating the discovery of potential biomarkers for wound healing, which may represent a breakthrough in this field and a major help in addressing delayed wound healing. In this review article, we aim to summarize the current progress achieved in host-microbiome crosstalk in the spectrum of CW healing and highlight future innovative strategies to boost the host immune response against infections, focusing on the interaction between pathogens and their hosts (for instance, by harnessing microorganisms like probiotics), which may serve as the prospective advancement of vaccines and treatments against infections.PMID:38731848 | DOI:10.3390/ijms25094629

<em>Lacticaseibacillus paracasei</em> JS-3 Isolated from "Jiangshui" Ameliorates Hyperuricemia by Regulating Gut Microbiota and iTS Metabolism

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 29;13(9):1371. doi: 10.3390/foods13091371.ABSTRACTBackground: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from "Jiangshui", a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3's UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3's role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the "Jiangshui" in Gansu, used for the treatment of hyperuricemia. It modulates host-microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.PMID:38731742 | DOI:10.3390/foods13091371

Widely Targeted Metabolomic Analysis Revealed the Diversity in Milk from Goats, Sheep, Cows, and Buffaloes and Its Association with Flavor Profiles

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 28;13(9):1365. doi: 10.3390/foods13091365.ABSTRACTThe milk flavor can be attributed to the presence of numerous flavor molecules and precursors. In this study, we employed widely targeted metabolomic analysis techniques to analyze the metabolic profiles of various milk samples obtained from goats, sheep, dairy cows, and buffaloes. A total of 631 metabolites were identified in the milk samples, which were further categorized into 16 distinct classes. Principal component analysis (PCA) suggested that the metabolite profiles of samples from the same species exhibit clustering, while separated patterns of metabolite profiles are observed across goat, sheep, cow, and buffalo species. The differential metabolites between the groups of each species were screened based on fold change and variable importance in projection (VIP) values. Five core differential metabolites were subsequently identified, including 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, inosine 5'-triphosphate, methylcysteine, N-cinnamylglycine, and small peptide (L-tyrosine-L-aspartate). Through multiple comparisons, we also screened biomarkers of each type of milk. Our metabolomic data showed significant inter-species differences in the composition and concentration of some compounds, such as organic acids, amino acids, sugars, nucleotides, and their derivatives, which may affect the overall flavor properties of the milk sample. These findings provided insights into the molecular basis underlying inter-species variations in milk flavor.PMID:38731736 | DOI:10.3390/foods13091365

Research of Processing Technology of Longjing Tea with 'Baiye 1' Based on Non-Targeted Aroma Metabolomics

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 26;13(9):1338. doi: 10.3390/foods13091338.ABSTRACTLongjing tea is favored by consumers due to its refreshing and delicate aroma, as well as its fresh and sweet flavor. In order to study the processing technology of Longjing tea with 'Baiye 1' tea varieties, solid phase microextraction and gas chromatography-mass spectrometry were used to analyze the volatile components of Longjing tea in different process stages. The results revealed the identification of 275 aroma metabolites in the processing samples of Longjing tea. The sensory evaluation and principal component analysis revealed that the leaves of fresh (XY) and spreading (TF) were different from the leaves of first panning (YQ), second panning (EQ), final panning (HG), and fragrance enhancing (TX). The relative contents of geraniol (1199.95 and 1134.51), linalool (745.93 and 793.98), methyl salicylate (485.22 and 314.67), phenylethyl alcohol (280.14 and 393.98), 2-methylfuran (872.28 and 517.96), 2-butenal (56.01 and 154.60), and 2-hexenal (46.22 and 42.24), refreshing and floral substances in the XY and TF stages, were higher than other stages. The aroma contents of 2-methylfuran, furfural, 2-methyl-1-penten-3-one, 3-hexen-2-one, dodecane, hexanoyl hexanoate, 2,5-dimethyl-pyrazine, and methyl-pyrazine were found to be significantly positively correlated with the intensity of chestnut aroma. In conclusion, this study contributes to a better understanding of the composition and formation mechanism of chestnut-like aroma and provides new insights into the processing technology to improve the quality of albino green tea.PMID:38731709 | DOI:10.3390/foods13091338

Gut Microbiota-Derived Tryptophan Metabolites Alleviate Allergic Asthma Inflammation in Ovalbumin-Induced Mice

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 26;13(9):1336. doi: 10.3390/foods13091336.ABSTRACTAsthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.PMID:38731707 | DOI:10.3390/foods13091336

Metabolome and Transcriptome Association Analysis Reveals Mechanism of Synthesis of Nutrient Composition in Quinoa (Chenopodium quinoa Willd.) Seeds

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 26;13(9):1325. doi: 10.3390/foods13091325.ABSTRACTQuinoa (Chenopodium quinoa Willd.) seeds are rich in nutrition, superior to other grains, and have a high market value. However, the biosynthesis mechanisms of protein, starch, and lipid in quinoa grain are still unclear. The objective of this study was to ascertain the nutritional constituents of white, yellow, red, and black quinoa seeds and to employ a multi-omics approach to analyze the synthesis mechanisms of these nutrients. The findings are intended to furnish a theoretical foundation and technical support for the biological breeding of quinoa in China. In this study, the nutritional analysis of white, yellow, red, and black quinoa seeds from the same area showed that the nutritional contents of the quinoa seeds were significantly different, and the protein content increased with the deepening of color. The protein content of black quinoa was the highest (16.1 g/100 g) and the lipid content was the lowest (2.7 g/100 g), among which, linoleic acid was the main fatty acid. A combined transcriptome and metabolome analysis exhibited that differentially expressed genes were enriched in "linoleic acid metabolism", "unsaturated fatty acid biosynthesis", and "amino acid biosynthesis". We mainly identified seven genes involved in starch synthesis (LOC110716805, LOC110722789, LOC110738785, LOC110720405, LOC110730081, LOC110692055, and LOC110732328); five genes involved in lipid synthesis (LOC110701563, LOC110699636, LOC110709273, LOC110715590, and LOC110728838); and nine genes involved in protein synthesis (LOC110710842, LOC110720003, LOC110687170, LOC110716004, LOC110702086, LOC110724454 LOC110724577, LOC110704171, and LOC110686607). The data presented in this study based on nutrient, transcriptome, and metabolome analyses contribute to an enhanced understanding of the genetic regulation of seed quality traits in quinoa, and provide candidate genes for further genetic improvements to improve the nutritional value of quinoa seeds.PMID:38731698 | DOI:10.3390/foods13091325

Metabolomics on Apple (Malus domestica) Cuticle-Search for Authenticity Markers

Sat, 11/05/2024 - 12:00
Foods. 2024 Apr 24;13(9):1308. doi: 10.3390/foods13091308.ABSTRACTThe profile of secondary metabolites present in the apple cuticular layer is not only characteristic of a particular apple cultivar; it also dynamically reflects various external factors in the growing environment. In this study, the possibility of authenticating apple samples by analyzing their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. A total of 274 authentic apple samples from four cultivars harvested in the Czech Republic and Poland between 2020 and 2022 were analyzed. The complex data generated, processed using univariate and multivariate statistical methods, enabled the building of classification models to distinguish apple cultivars as well as their geographical origin. The models showed very good performance in discriminating Czech and Polish samples for three out of four cultivars: "Gala", "Golden Delicious" and "Idared". Moreover, the validity of the models was tested over several harvest seasons. In addition to metabolites of the triterpene biosynthetic pathway, the diagnostic markers were mainly wax esters. "Jonagold", which is known to be susceptible to mutations, was the only cultivar for which an unambiguous classification of geographical origin was not possible.PMID:38731678 | DOI:10.3390/foods13091308

Untargeted Metabolomics Based on Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Differential Metabolite Analysis of Pinelliae Rhizoma and Its Adulterants

Sat, 11/05/2024 - 12:00
Molecules. 2024 May 6;29(9):2155. doi: 10.3390/molecules29092155.ABSTRACTThe present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.PMID:38731650 | DOI:10.3390/molecules29092155

Ultrasonic-Assisted Extraction of Xanthorrhizol from <em>Curcuma xanthorrhiza</em> Roxb. Rhizomes by Natural Deep Eutectic Solvents: Optimization, Antioxidant Activity, and Toxicity Profiles

Sat, 11/05/2024 - 12:00
Molecules. 2024 May 1;29(9):2093. doi: 10.3390/molecules29092093.ABSTRACTXanthorrhizol, an important marker of Curcuma xanthorrhiza, has been recognized for its different pharmacological activities. A green strategy for selective xanthorrhizol extraction is required. Herein, natural deep eutectic solvents (NADESs) based on glucose and organic acids (lactic acid, malic acid, and citric acid) were screened for the extraction of xanthorrhizol from Curcuma xanthorrhiza. Ultrasound-assisted extraction using glucose/lactic acid (1:3) (GluLA) gave the best yield of xanthorrhizol. The response surface methodology with a Box-Behnken Design was used to optimize the interacting variables of water content, solid-to-liquid (S/L) ratio, and extraction to optimize the extraction. The optimum conditions of 30% water content in GluLA, 1/15 g/mL (S/L), and a 20 min extraction time yielded selective xanthorrhizol extraction (17.62 mg/g) over curcuminoids (6.64 mg/g). This study indicates the protective effect of GluLA and GluLA extracts against oxidation-induced DNA damage, which was comparable with those obtained for ethanol extract. In addition, the stability of the xanthorrhizol extract over 90 days was revealed when stored at -20 and 4 °C. The FTIR and NMR spectra confirmed the hydrogen bond formation in GluLA. Our study reported, for the first time, the feasibility of using glucose/lactic acid (1:3, 30% water v/v) for the sustainable extraction of xanthorrhizol.PMID:38731583 | DOI:10.3390/molecules29092093

Objective Quantification Technique and Widely Targeted Metabolomics-Based Analysis of the Effects of Different Saccharidation Processes on Preserved French Plums

Sat, 11/05/2024 - 12:00
Molecules. 2024 Apr 26;29(9):2011. doi: 10.3390/molecules29092011.ABSTRACTVacuum saccharification significantly affected the flavor and color of preserved French plums. However, the correlation between color, flavor, and metabolites remains unclear. Metabolites contribute significantly to enhancing the taste and overall quality of preserved French plums. This study aimed to investigate the distinctive metabolites in samples from various stages of the processing of preserved French plums. The PCF4 exhibited the highest appearance, overall taste, and chroma. Furthermore, utilizing UPLC and ESI-Q TRAP-MS/MS, a comprehensive examination of the metabolome in the processing of preserved French plums was conducted. A total of 1776 metabolites were analyzed. Using WGCNA, we explored metabolites associated with sensory features through 10 modules. Based on this, building the correlation of modules and objective quantification metrics yielded three key modules. After screening for 151 differentiated metabolites, amino acids, and their derivatives, phenolic acids, flavonoids, organic acids, and other groups were identified as key differentiators. The response of differential metabolites to stress influenced the taste and color properties of preserved prunes. Based on these analyses, six important metabolic pathways were identified. This study identified changes in the sensory properties of sugar-stained preserved prunes and their association with metabolite composition, providing a scientific basis for future work to improve the quality of prune processing.PMID:38731502 | DOI:10.3390/molecules29092011

HPLC-Based Metabolomic Analysis and Characterization of Amaranthus cruentus Leaf and Inflorescence Extracts for Their Antidiabetic and Antihypertensive Potential

Sat, 11/05/2024 - 12:00
Molecules. 2024 Apr 26;29(9):2003. doi: 10.3390/molecules29092003.ABSTRACTThe aim of this study was to investigate the potential of Amaranthus cruentus flavonoids (quercetin, kaempferol, catechin, hesperetin, naringenin, hesperidin, and naringin), cinnamic acid derivatives (p-coumaric acid, ferulic acid, and caffeic acid), and benzoic acids (vanillic acid and 4-hydroxybenzoic acid) as antioxidants, antidiabetic, and antihypertensive agents. An analytical method for simultaneous quantification of flavonoids, cinnamic acid derivatives, and benzoic acids for metabolomic analysis of leaves and inflorescences from A. cruentus was developed with HPLC-UV-DAD. Evaluation of linearity, limit of detection, limit of quantitation, precision, and recovery was used to validate the analytical method developed. Maximum total flavonoids contents (5.2 mg/g of lyophilized material) and cinnamic acid derivatives contents (0.6 mg/g of lyophilized material) were found in leaves. Using UV-Vis spectrophotometry, the maximum total betacyanin contents (74.4 mg/g of lyophilized material) and betaxanthin contents (31 mg/g of lyophilized material) were found in inflorescences. The leaf extract showed the highest activity in removing DPPH radicals. In vitro antidiabetic activity of extracts was performed with pancreatic α-glucosidase and intestinal α-amylase, and compared to acarbose. Both extracts exhibited a reduction in enzyme activity from 57 to 74%. Furthermore, the in vivo tests on normoglycemic murine models showed improved glucose homeostasis after sucrose load, which was significantly different from the control. In vitro antihypertensive activity of extracts was performed with angiotensin-converting enzyme and contrasted to captopril; both extracts exhibited a reduction of enzyme activity from 53 to 58%. The leaf extract induced a 45% relaxation in an ex vivo aorta model. In the molecular docking analysis, isoamaranthin and isogomphrenin-I showed predictive binding affinity for α-glucosidases (human maltase-glucoamylase and human sucrase-isomaltase), while catechin displayed binding affinity for human angiotensin-converting enzyme. The data from this study highlights the potential of A. cruentus as a functional food.PMID:38731493 | DOI:10.3390/molecules29092003

The Potential Antinociceptive Effect and Mechanism of <em>Cannabis sativa</em> L. Extract on Paclitaxel-Induced Neuropathic Pain in Rats Uncovered by Multi-Omics Analysis

Sat, 11/05/2024 - 12:00
Molecules. 2024 Apr 25;29(9):1958. doi: 10.3390/molecules29091958.ABSTRACTCannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.PMID:38731449 | DOI:10.3390/molecules29091958

The Effect of α-Arbutin on UVB-Induced Damage and Its Underlying Mechanism

Sat, 11/05/2024 - 12:00
Molecules. 2024 Apr 23;29(9):1921. doi: 10.3390/molecules29091921.ABSTRACTUltraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1β, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.PMID:38731413 | DOI:10.3390/molecules29091921

Electropositive Citric Acid-Polyethyleneimine Carbon Dots Carrying the PINK1 Gene Regulate ATP-Related Metabolic Dysfunction in APP/PS1-N2a Cells

Sat, 11/05/2024 - 12:00
Molecules. 2024 Apr 23;29(9):1907. doi: 10.3390/molecules29091907.ABSTRACT(1) Background: Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) peptide accumulation and mitochondrial dysfunction during the early stage of disease. PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1/Parkin pathway, Na+/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP/PS1-N2a cells and reduced reactive-oxygen-species generation and Aβ1-40 and Aβ1-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing Aβ1-40 and Aβ1-42, and increasing ATP production.PMID:38731398 | DOI:10.3390/molecules29091907

The Effects of Lentinan on the Hematological and Immune Indices of Dairy Cows

Sat, 11/05/2024 - 12:00
Animals (Basel). 2024 Apr 27;14(9):1314. doi: 10.3390/ani14091314.ABSTRACTIn this study, we investigated the effects of lentinan (LNT) on hematological parameters, immune indices, and metabolite levels in dairy cows. We randomly assigned forty Holstein cows to four treatment groups. The treatments consisted of 0, 5, 10, and 15 g/d of LNT. Compared with the control group, the addition of 10 g/d of LNT decreased the content of ALT and IL-8 but simultaneously increased the content of IL-4 in the cows' serum. Supplementation with 10 g/d of LNT decreased the levels of lymphocyte, RDW, ALT, AST, TC, IL-2, and IL-8, but, concurrently, in-creased the levels of granulocytes and IL-4 in their serum. In addition, supplementation with 15 g/d of LNT decreased the levels of RDW, TC, IL-2, and IL-8, but, at the same time, increased the levels of IL-4 and IgM in their serum. For the metabolomic analysis, cows fed with 0 and 10 g/d of LNT were selected. The results showed that 10 metabolites, including reduced nicotinamide riboside and trehalose, were upregulated in the 10 g/d group. These differential metabolites were enriched in tyrosine metabolism and trehalose degradation and altered two metabolic pathways of ubiquinone and other terpene quinone biosynthesis, as well as starch and sucrose metabolism. These findings provide evidence that LNT could be used to reduce the risk of inflammation in dairy cows.PMID:38731317 | DOI:10.3390/ani14091314

β-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (<em>Danio rerio</em>) Model

Sat, 11/05/2024 - 12:00
Animals (Basel). 2024 Apr 25;14(9):1289. doi: 10.3390/ani14091289.ABSTRACTOBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood.METHODS: A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of β-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics.RESULTS: β-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in β-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. β-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of β-sitosterol significantly inhibited the expression of Ppar-γ and Rxr-α in the zebrafish model by at least 50% and 25%, respectively.CONCLUSIONS: β-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.PMID:38731293 | DOI:10.3390/ani14091289

Multi-Omics Analysis Reveals the Regulatory Mechanism of Probiotics on the Growth Performance of Fattening Sheep

Sat, 11/05/2024 - 12:00
Animals (Basel). 2024 Apr 24;14(9):1285. doi: 10.3390/ani14091285.ABSTRACTProbiotics have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of probiotic supplementation on the growth performance; rumen and intestinal microbiota; rumen fluid, serum, and urine metabolism; and rumen epithelial cell transcriptomics of fattening meat sheep. Twelve Hu sheep were selected and randomly divided into two groups. They were fed a basal diet (CON) or a basal diet supplemented with 1.5 × 108 CFU/g probiotics (PRB). The results show that the average daily weight gain, and volatile fatty acid and serum antioxidant capacity concentrations of the PRB group were significantly higher than those of the CON group (p < 0.05). Compared to the CON group, the thickness of the rumen muscle layer in the PRB group was significantly decreased (p < 0.01); the thickness of the duodenal muscle layer in the fattening sheep was significantly reduced; and the length of the duodenal villi, the thickness of the cecal and rectal mucosal muscle layers, and the thickness of the cecal, colon, and rectal mucosal layers (p < 0.05) were significantly increased. At the genus level, the addition of probiotics altered the composition of the rumen and intestinal microbiota, significantly upregulating the relative abundance of Subdivision5_genera_incertae_sedis and Acinetobacter in the rumen microbiota, and significantly downregulating the relative abundance of Butyrivibrio, Saccharofermentans, and Fibrobacter. The relative abundance of faecalicoccus was significantly upregulated in the intestinal microbiota, while the relative abundance of Coprococcus, Porphyromonas, and Anaerobacterium were significantly downregulated (p < 0.05). There were significant differences in the rumen, serum, and urine metabolites between the PRB group and the CON group, with 188, 138, and 104 metabolites (p < 0.05), mainly affecting pathways such as vitamin B2, vitamin B3, vitamin B6, and a series of amino acid metabolisms. The differential genes in the transcriptome sequencing were mainly enriched in protein modification regulation (especially histone modification), immune function regulation, and energy metabolism. Therefore, adding probiotics improved the growth performance of fattening sheep by altering the rumen and intestinal microbiota; the rumen, serum, and urine metabolome; and the transcriptome.PMID:38731289 | DOI:10.3390/ani14091285

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