Mechanism of Salvia miltiorrhiza Bunge extract to alleviate Chronic Sleep Deprivation-Induced cognitive dysfunction in rats.

BACKGROUND: Bidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PURPOSE: The purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. METHODS: DS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. RESULTS: We demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1ß, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. CONCLUSION: DS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.

Comparative analysis of the synergetic effects of Diwuyanggan prescription on high fat diet-induced non-alcoholic fatty liver disease using untargeted metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide and had no approved pharmacological treatments. Diwuyanggan prescription (DWYG) is a traditional Chinese medicine preparation composed of 5 kinds of herbs, which has been used for treating chronic liver diseases in clinic. Whereas, the synergistic mechanism of this prescription for anti-NAFLD remains unclear. In this study, we aimed to demonstrate the synergetic effect of DWYG by using the disassembled prescriptions and untargeted metabolomics research strategies. The therapeutic effects of the whole prescription of DWYG and the individual herb were divided into six groups according to the strategy of disassembled prescriptions, including DWYG, Artemisia capillaris Thunb. (AC), Curcuma longa L. (CL), Schisandra chinensis Baill. (SC), Rehmannia glutinosa Libosch. (RG) and Glycyrrhiza uralensis Fisch. (GU) groups. The high fat diets-induced NAFLD mice model was constructed to evaluate the efficacy effects of DWYG. An untargeted metabolomics based on the UPLC-QTOF-MS/MS approach was carried out to make clear the synergetic effect on the regulation of metabolites dissecting the united mechanisms. Experimental results on animals revealed that the anti-NAFLD effect of DWYG prescription was better than the individual herb group in reducing liver lipid deposition and restoring the abnormality of lipidemia. In addition, further metabolomics analysis indicated that 23 differential metabolites associated with the progression of NAFLD were identified and 19 of them could be improved by DWYG. Compared with five single herbs, DWYG showed the most extensive regulatory effects on metabolites and their related pathways, which were related to lipid and amino acid metabolisms. Besides, each individual herb in DWYG was found to show different degrees of regulatory effects on NAFLD and metabolic pathways. SC and CL possessed the highest relationship in the regulation of NAFLD. Altogether, these results provided an insight into the synergetic mechanisms of DWYG from the metabolic perspective, and also supported a scientific basis for the rationality of clinical use of this prescription.

Elucidating the mechanisms underlying the anti-hyperlipidemic effects of Laportea bulbifera using integrated serum metabolomics and network pharmacology.

Hyperlipidemia is a chronic metabolic disorder characterized by alterations in lipid metabolism as well as other pathways. Laportea bulbifera, an indigenous medicinal plant of Chinese herbal medicine, exhibits therapeutic effects on hyperlipidemia, but the mechanisms remain unclear. This study investigated the potential mechanisms underlying the anti-hyperlipidemic effects of L. bulbifera using an integrated strategy based on metabolomics and network pharmacology methods that were established to investigate the potential mechanism of anti-hyperlipidemia effect of L. bulbifera. First, the therapeutic effects of L. bulbifera on body weight reduction and biochemical indices were assessed. Next, 18 significant metabolites distinguishing the control and model groups were identified based on serum metabolomics and multivariate analyses. Then, a compound-target network was constructed by linking L. bulbifera and hyperlipidemia using network pharmacology. Three metabolic pathways involved in treating hyperlipidemia were identified. Finally, five crucial targets were selected by constructing a bionetwork starting from the compounds and ending in the metabolites. This study established an integrated strategy based on metabolomics coupled with network pharmacology and revealed the mechanism underlying the protective effects of L. bulbifera against hyperlipidemia for the first time.

Dynamical changes of tea metabolites fermented by Aspergillus cristatus, Aspergillus neoniger and mixed fungi: A temporal clustering strategy for untargeted metabolomics.

Dark tea fermentation involves various fungi, but studies focusing on the mixed fermentation in tea remain limited. This study investigated the influences of single and mixed fermentation on the dynamical alterations of tea metabolites. The differential metabolites between unfermented and fermented teas were determined using untargeted metabolomics. Dynamical changes in metabolites were explored by temporal clustering analysis. Results indicated that Aspergillus cristatus (AC) at 15 days, Aspergillus neoniger (AN) at 15 days, and mixed fungi (MF) at 15 days had respectively 68, 128 and 135 differential metabolites, compared with unfermentation (UF) at 15 days. Most of metabolites in the AN or MF group showed a down-regulated trend in cluster 1 and 2, whereas most of metabolites in the AC group showed an up-regulated trend in cluster 3 to 6. The three key metabolic pathways mainly composed of flavonoids and lipids included flavone and flavonol biosynthesis, glycerophospholipid metabolism and flavonoid biosynthesis. Based on the dynamical changes and metabolic pathways of the differential metabolites, AN showed a predominant status in MF compared with AC. Together, this study will advance the understanding of dynamic changes in tea fermentation and provide valuable insights into the processing and quality control of dark tea.

Diet Restriction Impact on High-Fat-Diet-Induced Obesity by Regulating Mitochondrial Cardiolipin Biosynthesis and Remodeling.

Diet restriction (DR) ameliorates obesity by regulating mitochondrial function. Cardiolipin (CL), a mitochondrial phospholipid, is closely associated with mitochondrial function. This study aimed to evaluate the anti-obesity effects of graded levels of DR based on mitochondrial CL levels in the liver. Obese mice were treated with 0%, 20%, 40%, and 60% reductions in the normal diet compared to normal animals (0 DR, 20 DR, 40 DR, and 60 DR groups, respectively). Biochemical and histopathological analyses were performed to evaluate the ameliorative effects of DR on obese mice. The altered profile of mitochondrial CL in the liver was explored using a targeted metabolomics strategy by ultra-high-pressure liquid chromatography MS/MS coupled with quadrupole time-of-flight mass spectrometry. Finally, gene expression associated with CL biosynthesis and remodeling was quantified. Tissue histopathology and biochemical index evaluations revealed significant improvements in the liver after DR, except for the 60 DR group. The variation in mitochondrial CL distribution and DR levels showed an inverted U-shape, and the CL content in the 40 DR group was the most upregulated. This result is consistent with the results of the target metabolomic analysis, which showed that 40 DR presented more variation. Furthermore, DR led to increased gene expression associated with CL biosynthesis and remodeling. This study provides new insights into the mitochondrial mechanisms underlying DR intervention in obesity.

Exploration of the hypoglycemic mechanism of Fuzhuan brick tea based on integrating global metabolomics and network pharmacology analysis.

Introduction: Fuzhuan brick tea (FBT) is a worldwide popular beverage which has the appreciable potential in regulating glycometabolism. However, the reports on the hypoglycemic mechanism of FBT remain limited. Methods: In this study, the hypoglycemic effect of FBT was evaluated in a pharmacological experiment based on Kunming mice. Global metabolomics and network pharmacology were combined to discover the potential target metabolites and genes. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed for verification. Results: Seven potential target metabolites and six potential target genes were screened using the integrated approach. After RT-qPCR analysis, it was found that the mRNA expression of VEGFA, KDR, MAPK14, and PPARA showed significant differences between normal and diabetes mellitus mice, with a retracement after FBT treatment. Conclusion: These results indicated that the hypoglycemic effect of FBT was associated with its anti-inflammatory activities and regulation of lipid metabolism disorders. The exploration of the hypoglycemic mechanism of FBT would be meaningful for its further application and development.

Sex Differences of Cardiolipin in Tissue Distribution Based on Targeted Lipidomic Analysis by UHPLC-QTOF-MS/MS.

Cardiolipins (CLs) are involved in ATP production, mitochondria biogenesis, apoptosis and mitophagy. Their tissue distribution can provide insight into the function of mitochondria and related diseases. However, the reports on tissue distribution of CLs remain limited. In this research, CLs were identified from heart, liver, kidney, spleen, lung, skeletal muscle, and brain using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS). Then, the distribution and sex difference of CLs in seven tissues were compared by a targeted lipidomic approach. A total of 88 CLs were identified, of which 58, 51, 57, 58, 50, 61 and 52 CLs were found in heart, liver, kidney, spleen, lung, skeletal muscle, and brain, respectively. Compared with the distribution of CLs in heart, liver, kidney, and skeletal muscle, the CLs in spleen, lung, and brain showed significant differences. Moreover, the results indicated that there were sex differences of CLs in liver and kidney. A total of 16 CLs in liver tissue and 21 CLs in kidney tissue, with significant sex differences, were screened. Our findings in the targeted lipidomic analysis demonstrated that tissue distribution of CLs was essential in the dynamic states and sex differences of CLs, which might provide evidence for the mitochondrial-related mechanism under physiological and pathological conditions.

Supplementation with Ginseng, Lilii Bulbus, and Poria induces alterations in the serum metabolic profile of healthy adults.

The preventive and therapeutic effects of herbal supplementation containing Ginseng, Lilii Bulbus, and Poria (GLP) on inflammation and oxidative stress in healthy adults have been demonstrated in our previous studies. However, the underlying mechanisms of organism protection by GLP remain unclarified, and few studies have used metabolomics to investigate comprehensive changes before and after GLP supplementation. Based on previous research, we conducted a placebo-controlled trial among 82 healthy adults in Wuhan, China, using a metabolomics approach with ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) and multivariate statistical methods to analyze serum metabolite alterations in participants before and after GLP supplementation. Furthermore, 14 discriminant metabolites related to lipid metabolism, inflammation and oxidative stress, energy metabolism, and coenzyme A metabolism were significantly different between the before- and after-GLP groups (P < 0.0001). Nine metabolites were significantly decreased in the serum samples from the after-GLP group compared with the before-GLP group, while five metabolites were significantly increased. These metabolites could be critical components associated with the anti-inflammatory, antioxidant, and hypolipidemic activities of GLP, indicating the potential complementary role of GLP supplements in the primary prevention of dysfunctional metabolism caused by potential diseases such as cardiovascular disease. This study provides a valuable reference for cardiovascular health protection and disease prevention.

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective: CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods: In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results: Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions: An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Potential hypoglycemic metabolites in dark tea fermented by Eurotium cristatum based on UPLC-QTOF-MS/MS combining global metabolomic and spectrum-effect relationship analyses.

The preventive and therapeutic effects of dark tea fermented by Eurotium cristatum (DTE) in glucose metabolism have been demonstrated. However, few studies have investigated comprehensive changes in the chemical composition and activity in DTE before and after fermentation. In this study, the metabolic profiling of raw samples and fermented samples was determined by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Furthermore, a systematic analytical strategy combining global metabolomics and the spectrum-effect relationship based on α-glucosidase inhibition was employed for screening discriminant metabolites. As a result, 15 discriminant metabolites were identified in DTE samples. Among them, 10 metabolites (4 fatty acids, 1 dyphylline derivative, 3 lysophosphatidylcholines, and 2 triterpenes) increased in relative contents and the contents of the other 5 polyphenol metabolites decreased after fermentation. These metabolites were critical constituents possibly associated with DTE's hypoglycemic activity, which also might be suitable as quality evaluation indicators. This study provided a worthy insight into the exploration of representative active constituents or quality indicators of DTE.

Associations of urine metals and metal mixtures during pregnancy with cord serum vitamin D Levels: A prospective cohort study with repeated measurements of maternal urinary metal concentrations.

BACKGROUND: Vitamin D deficiency has been associated with the increased risk of many diseases, especially during early life. Exposure to some toxic metals may decrease vitamin D levels in adults and children in previous studies. However, less is known about the associations of maternal metals exposure during pregnancy with newborns' vitamin D status. OBJECTIVE: We conducted a prospective cohort study to investigate the relationships between urine metals and metal mixtures during pregnancy and newborns' vitamin D status. METHODS: Urine samples of 598 pregnant women were collected in each trimester and cord blood samples of newborns were collected at delivery. The concentrations of 20 metals in urine and 25-hydroxyvitamin D [25(OH)D] in cord serum were quantified. Generalized linear models were used to estimate the associations between individual metals and cord serum total 25(OH)D. We applied Bayesian Kernel Machine Regression (BKMR) to evaluate the mixture and interaction effects of urine metals. RESULTS: In individual metals analyses, we reported that a double increase in urine vanadium (V), cobalt (Co), and thallium (Tl) throughout pregnancy was associated with a 9.91% [95% confidence interval (CI): -18.58%, -0.30%], 11.42% (95% CI: -17.73%, -4.63%), and 12.64% (95% CI: -21.44%, -2.86%) decrease in cord serum total 25(OH)D, respectively. Exposures to the three metals during the whole pregnancy were also correlated to increased odds for newborns' vitamin D deficiency (<20 ng/mL) [odds ratio (95% CI): 1.80 (1.05, 3.10) for V, 1.88 (1.25, 2.82) for Co, and 1.90 (1.07, 3.38) for Tl]. BKMR analyses revealed a negative influence of metal mixtures (V+Co+Tl) on neonatal vitamin D status, as well as potential synergism between V and Co and between V and Tl. CONCLUSIONS: Our study provides evidence of negative impacts of maternal exposure to V, Co, and Tl during pregnancy on cord serum vitamin D levels at delivery. Potential synergism between V and Co and between V and Tl existed in their associations with cord serum total 25(OH)D.

Fine particulate matter exposure and perturbation of serum metabolome: A longitudinal study in Baoding, China.

Metabolomics represents a powerful tool for measuring environmental exposures and biological responses to unveil potential mechanisms. Few studies have investigated the effects of exposure to fine particulate matter (PM2.5) longitudinally on serum metabolomics in regions with high-level PM2.5. Therefore, we examined the changes of serum metabolomics corresponding to individual PM2.5 exposure levels in spring and autumn among 63 healthy college students in Baoding city, Hebei, China. The metabolic profiling was determined by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The average level of individual PM2.5 in the spring was 1.82-fold higher than in the autumn (240 µg/m3 vs 132 µg/m3). Males were exposed to a higher level of PM2.5 than females in the spring. Metabolic profiling was clearly separated by orthogonal partial least square-discriminant analysis in males but not in females. In the analysis of the associations between the metabolome and PM2.5 of the two seasons, the changes of 14 serum metabolites were significantly associated with PM2.5 in males. The metabolites related to heme metabolism (bilirubin, biliverdin), energy metabolism and oxidative stress (2-Octenoylcarnitine, N-Heptanoylglycine, and acetylcysteine), phospholipid metabolism (lysophosphatidic acid, phospholipid acid, and lysophosphatidylethanolamine), and tryptophan metabolism (N-Acetylserotonin, indolepyruvate, and melatonin) were decreased in the range of 2.16%-6.80% for each 10 µg/m3 increase of PM2.5, while thyrotropin-releasing hormone, glutathione, and phosphatidylethanolamine related to energy metabolism and oxidative stress, and phospholipid metabolism were increased in the range of 2.95%-4.90% for each 10 µg/m3 increase of PM2.5. This longitudinal study suggests that higher PM2.5 exposure may induce perturbations in serum metabolic signaling related to oxidative stress and inflammation, and males may be more prone to these metabolic perturbations.

Changes in Triterpenes in Alismatis rhizoma after Processing Based on Targeted Metabolomics Using UHPLC-QTOF-MS/MS.

Alismatis rhizoma (AR) has been used as an herbal medicine in China for over a thousand years. Crude AR, salt-processed AR (SAR), and bran-processed AR (BAR) are recorded in the Pharmacopoeia of the People's Republic of China. However, the differences of chemical composition between crude AR and its processing products remain limited. In this study, triterpenes were identified from crude AR, SAR, and BAR by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight-mass spectrometer (UHPLC-QTOF-MS/MS). Subsequently, the differences of triterpenes between the crude AR and processed ARs were compared via a targeted metabolomics approach. Finally, a total of 114 triterpenes were identified, of which 83, 100, and 103 triterpenes were found in crude AR, SAR, and BAR, respectively. After salt-processing, there were 17 triterpenes newly generated, 7 triterpenes with trends of increasing, and 37 triterpenes decreased. Meanwhile, 56 triterpenes including 21 newly generated and 35 with significant increases were observed in BAR. This study could be benefit to investigate the processing mechanism of AR, as well as support their clinical applications.

Associations between six common per- and polyfluoroalkyl substances and estrogens in neonates of China.

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms.

Association between exposure to per- and polyfluoroalkyl substances and blood glucose in pregnant women.

Increasing evidence shows that exposure to per- and polyfluoroalkyl substances (PFASs), common and persistent anthropogenic pollutants, may affect glucose homeostasis. However, data is limited for pregnant women, and it is less clear how novel fluorinated pollutants affect glucose homeostasis during pregnancy. Our goal was to investigate the relationships of exposure to13 PFASs including some novel fluorinated pollutants with blood glucose in 874 Chinese pregnant women from the general population. We measured blood glucose following an oral glucose tolerance test (OGTT) in the second trimester and quantified PFAS concentrations in umbilical cord blood. The associations of PFAS exposure with fasting, 1-h OGTT and 2-h OGTT glucose were examined using the general linear regression model. For every doubling of perfluorobutane sulfonate (PFBS), a short-chain PFAS, the 1-h and 2-h OGTT blood glucose increased 0.09 mmol/L (ß = 0.09, 95%CI: 0.02, 0.17) and 0.07 mmol/L (ß = 0.07, 95%CI: 0.01, 0.13), respectively. In addition, perfluoroheptanoate (PFHpA), an alternative of perfluorooctanoate (PFOA), was positively associated with fasting glucose (ß = 0.07, 95%CI: 0.02, 0.13; high vs low). Higher levels of PFAS exposure were related to increased blood glucose in pregnant women, indicating PFAS exposure may impair glucose homeostasis during pregnancy.

The hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced diabetic mice and their active components characterized by LC-QTOF-MS/MS.

Fuzhuan Brick-Tea is a postfermented product with the hypoglycemic effect, which is prepared from the leaves of Camellia sinensis var. sinensis. However, the material basis associated with the hypoglycemic effect was not clear. The present research was designed to explore the hypoglycemic effect of extract/fractions from Fuzhuan Brick-Tea in streptozotocin-induced type II diabetic mice. Then an ultra-high pressure liquid chromatography along with quadrupole time of flight mass spectrometry was used to analyze the phytochemicals in Fuzhuan Brick-Tea fractions. As a result, the hypoglycemic and hypolipidemic effects were evidently observed from the serum biochemical indexes and liver pathological examination in type II diabetic mice. In addition, there were total of 20 major components including eight lysophosphatidylcholines (Lyso-PCs), five fatty acids, and seven novel theophylline derivatives tentatively identified in the active fraction from water extract. Therefore, these components were assumed to contribute partly to the hypoglycemic effect of Fuzhuan Brick-Tea. These findings also give the evidence that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. PRACTICAL APPLICATION: This study suggests that the Lyso-PCs, fatty acids, and novel theophylline derivatives in Fuzhuan Brick-Tea may provide benefits in ameliorating disorders of glucose and lipid metabolism. It can be taken as a beneficial diet additive or nutraceutical.

Associations between Phase Angle Values Obtained by Bioelectrical Impedance Analysis and Nonalcoholic Fatty Liver Disease in an Overweight Population.

Objective: There is a limited diagnosis of nonalcoholic fatty liver disease (NAFLD). Thus, the noninvasive assessments are worth exploring. We determined the associations of phase angles (PhAs) obtained from bioelectric impedance analysis (BIA) with the risk of NAFLD in an overweight population. Methods: A study involving 953 overweight participants was conducted in Wuhan city, China. The associations between PhAs (right arm, left arm, body trunk, right leg, left leg, and whole body) and the risk of NAFLD were conducted using multivariate logistic regression analyses. The associations of PhAs with the controlled attenuation parameter (CAP), a noninvasive assessment of liver steatosis and fibrosis, were also evaluated by both linear and logistic regression analyses. Results: The PhA values of the whole body, trunk, and legs were significantly lower (P < 0.05) in the NAFLD group than the non-NAFLD group. After adjustment for BMI, gender, education, income/year, hyperlipidemia, hypertension, diabetes, smoking, passive smoking, and drinking, significant associations of PhA values of the right leg, left leg, and whole body with the risk of NAFLD were observed. In addition, the PhA of the right leg, left leg, and whole body were significantly related to the CAP values. Further stratified analyses indicated that these associations were significant in the participants with BMI <30, but not in the participants with BMI ≥30. Conclusions: PhAs might be effective indicators in the management of NAFLD among overweight people.

Associations of per-/polyfluoroalkyl substances with glucocorticoids and progestogens in newborns.

BACKGROUND: Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown. OBJECTIVE: To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns. METHODS: We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens [progesterone, 17-hydroxyprogesterone (17OHP)] in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR). RESULTS: Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement - 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone. CONCLUSIONS: In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns.

A novel predict-verify strategy for targeted metabolomics: Comparison of the curcuminoids between crude and fermented turmeric.

Curcuminoids are the major bioactive constituents of turmeric, the application of which are limited by the poor bioavailability. In this study, turmeric was fermented by the Monascus purpureus and Eurotium cristatum fungi to enhance its bioavailability. To explore the variations in the curcuminoids contents in fermented turmeric, a targeted predict-verify strategy was established. For targeted analysis of curcuminoids, a compound library containing all possible curcuminoids based on their structural skeleton was predicted and built for targeted scanning. Then, the MS data were automatically matched with the predicted library to verify the corresponding curcuminoids. As a result, 115 curcuminoids (48 novel compounds and 14 compounds reported in turmeric for the first time) were fully characterized in crude and fermented turmeric. Among these curcuminoids, 31 were newly generated in fermented turmeric. The established predict-verify strategy allows for an efficient and automatic metabolomic analysis to screen for curcuminoids with potentially better bioavailability.

The metabolic change in serum lysoglycerophospholipids intervened by triterpenoid saponins from Kuding tea on hyperlipidemic mice.

Triterpenoid saponins from Kuding tea have demonstrated preventive effects on hyperlipidaemia induced by a high-fat diet. Lysoglycerophospholipids (Lyso-GPLs) are known to be associated with proatherogenic conditions such as hyperlipidaemia. In this study, a target profiling strategy based on a multiple reaction monitoring mode was applied for the analysis of Lyso-GPLs. The metabolic changes were evaluated by the qualitative and relative quantitative distribution of six classes of Lyso-GPLs in mouse serum. A total of 153 Lyso-GPL regioisomers, consisting of 85 lysophosphatidylcholines, 15 lysophosphatidic acids, 23 lysophosphatidylethanolamines, 5 lysophosphatidylserines, 19 lysophosphatidylinositols and 6 lysophosphatidylglycerols, were detected and quantified. The results showed decreased trends in the content of total Lyso-GPLs in the serum of hyperlipidemic mice compared with that in normal controls. The content of total Lyso-GPLs significantly increased after treatment with triterpenoid saponins from Kuding tea. Among them, the proportions of most Lyso-GPLs with a higher degree of unsaturation or a longer carbon chain in fatty acyl chains dramatically decreased in hyperlipidemic mice. However, this tendency reversed after the treatment of triterpenoid saponins from Kuding tea. This is the first study regarding a target profiling strategy for the quantitative analysis of six different types of Lyso-GPLs on high-fat diet-induced hyperlipidemic mice intervened by Kuding tea. Those Lyso-GPLs changed significantly may be potential biomarkers for hyperlipidaemia, and involved in the mechanism of the preventive intervention of Kuding tea on Lipid metabolic diseases.