Current insights into the interplay between gut microbiota-derived metabolites and metabolic-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent and challenging disease associated with a significant health and economic burden. MAFLD has been subjected to and widely investigated in many studies; however, the underlying pathogenesis and its progression have yet to understand fully. Furthermore, precise biomarkers for diagnosing and specific drugs for treatment are yet to be discovered. Increasing evidence has proven gut microbiota as the neglected endocrine organ that regulates homeostasis and immune response. Targeting gut microbiota is an essential strategy for metabolic diseases, including MAFLD. Gut microbiota in the gut-liver axis is connected through tight bidirectional links through the biliary tract, portal vein, and systemic circulation, producing gut microbiota metabolites. This review focuses on the specific correlation between gut microbiota metabolites and MAFLD. Gut microbiota metabolites are biologically active in the host and, through subsequent changes and biological activities, provide implications for MAFLD. Based on the review studies, gut-liver axis related-metabolites including short-chain fatty acids, bile acids (BAs), lipopolysaccharide, choline and its metabolites, indole and its derivates, branched-chain amino acids, and methionine cycle derivates was associated with MAFLD and could be promising MAFLD diagnosis biomarkers, as well as the targets for MAFLD new drug discovery.

Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocytes.

BACKGROUND: Ischemia/reperfusion (I/R) is associated with severe cellular damage and death. Ferroptosis, a new form of regulated cell death caused by the accumulation of iron-mediated lipid peroxidation, has been found in several diseases including I/R injury, which was reported to be suppressed by flavonoids. Baicalein (BAI) and luteolin (Lut) are flavonoids and were shown to reduce the myocardial I/R injury. BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation. However, the anti-ferroptosis effect of Lut on ferroptosis has not been reported. This study aimed to investigate whether ferroptosis reduction contributes to the BAI- and Lut-protected cardiomyocytes. METHODS: This research used erastin, RSL3, and Fe-SP to induce ferroptosis. Cell viability was examined using MTT assay. Annexin V-FITC, CM-H2DCFDA, and Phen Green SK diacetate (PGSK) fluorescent intensity were detected to analyze apoptotsis, ROS levels, and Fe2+ concentrations, respectively. qPCR and Western blot analysis were conducted to detect the levels of mRNA and protein, respectively. RESULTS: Our data show that BAI and Lut protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. BAI and Lut reduced the I/R-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA. CONCLUSIONS: BAI and Lut could protect the cardiomyocytes against the I/R-induced ferroptosis via suppressing accumulation of ROS and MDA.

Statins as Repurposed Drugs in Gynecological Cancer: A Review.

Discovering new drugs is an expensive and time-consuming process, including target identification, bioavailability, pharmacokinetic (PK) tests, pharmacodynamic (PD) tests, toxicity profiles, recommended dosage test, and observation of the side effects, etc. Repurposed drugs could bypass some steps, starting from phase II trials, and shorten the processes. Statins, also known as HMG-CoA inhibitors (HMGCR), are commonly used to manage and prevent various cardiovascular diseases and have been shown to improve the morbidity and mortality of patients. In addition to the inhibitory effects on the production of cholesterol, the beneficial effects of statins on the prognosis and risk of various cancers are also shown. Statins not only inhibited cell proliferation, metastasis, and chemoresistance but affected the tumor microenvironment (TME). Thus, statins have great potential to be repurposed in oncology. Hence, we review the meta-analysis, cohort, and case-control studies of statins in gynecological cancers, and elucidate how statins regulate cell proliferation, apoptosis, tumor growth, and metastasis. Although the results in gynecological cancers remain controversial and the effects of different statins in different histotypes of gynecological cancers and TME are needed to elucidate further, statins are excellent candidates and worthy of being repurposed drugs in treating gynecological cancers.

Serum Trimethylamine N-Oxide Levels Correlate with Metabolic Syndrome in Coronary Artery Disease Patients.

Trimethylamine N-oxide (TMAO) is a gut microbial metabolite that affects atherogenesis and glucose dysregulation. The purpose of this study was to look at the link between blood TMAO levels and metabolic syndrome (MetS) in individuals with coronary artery disease (CAD). Blood samples were obtained in fasting status, and serum TMAO level was quantified by high-performance liquid chromatography-mass spectrometry. MetS and its components were defined according to the International Diabetes Federation diagnostic criteria. Of 92 enrolled patients, 51 (55.4%) had MetS. Patients with MetS had a greater proportion of hypertension and diabetes mellitus, higher body weight, waist circumference, body mass index, systolic blood pressure, fasting glucose, triglycerides, blood urea nitrogen, creatinine, C-reactive protein (CRP), insulin level, homeostasis model assessment of insulin resistance, and TMAO level. Multivariable logistic regression models revealed that TMAO level (odds ratio: 1.036, 95% confidence interval: 1.005-1.067, p = 0.023) could be an effective predictor of MetS among the CAD population. In these patients, the log-TMAO level was positively associated with log-CRP (ß = 0.274, p = 0.001) and negatively associated with eGFR (ß = -0.235, p = 0.022). In conclusion, our study revealed a positive association between serum TMAO level and MetS among patients with CAD.

Effects of an earplug placement intervention on sleep quality in patients in a medical intensive care unit: A randomized controlled trial.

AIMS: This study aimed to evaluate the effects of an intervention involving earplug placement during nocturnal sleep in non-ventilated intensive care unit patients. METHODS: A randomized controlled trial was conducted in 107 adult patients between January 2017 and December 2018. Participants in the intervention group (n = 55) slept with earplugs between 10 pm and 7 am on the second night of their intensive care unit stay. In the control group, participants slept with no earplugs. Outcome parameters included sleep, urinary 6-sulfatoxymelatonin levels, relaxation responses measured using the Richards-Campbell Sleep Questionnaire, liquid chromatography-mass spectrometry results and vital signs. Urine was collected between 10 pm and 7 am. RESULTS: Overall, 28.03% of participants showed virtually no 6-sulfatoxymelatonin excretion in the collected urine. Outcome parameters were not significantly different between the groups, indicating that wearing earplugs alone did not affect sleep quality, urinary 6-sulfatoxymelatonin and vital signs. CONCLUSIONS: The effects of using earplugs alone on sleep quality, urinary 6-sulfatoxymelatonin and relaxation responses in patients admitted to the intensive care unit were inconclusive. Additional research is required before earplugs alone can be widely used to improve sleep quality.

Association between serum indoxyl sulfate levels with carotid-femoral pulse wave velocity in patients with chronic kidney disease.

BACKGROUND: The role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear. MATERIALS AND METHODS: We investigated the association between serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography-mass spectrometry analysis. RESULTS: Of these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio [aOR] 1.436, 95% confidence interval [CI] 1.085-1.901, p = 0.011), age (aOR 1.058, 95% CI 1.021-1.097, p = 0.002), and SBP (aOR 1.019, 95%CI 1.000-1.038, p = 0.049) were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677 (95%CI 0.598-0.750, p = 0.0001) to predict the development of AS in patients with CKD. CONCLUSION: These finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD.

Determination of Major Endogenous FAHFAs in Healthy Human Circulation: The Correlations with Several Circulating Cardiovascular-Related Biomarkers and Anti-Inflammatory Effects on RAW 264.7 Cells.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly discovered long-chain fatty acids. However, the major endogenous FAHFAs in healthy human circulation, their correlation with cardiovascular (CV) biomarkers, and their anti-inflammatory effects have not been investigated and remain unclear. In the present study, a total of 57 healthy subjects were recruited. Liquid chromatography-mass spectrometry (LC-MS) was developed for the simultaneous determination of seven FAHFAs, four long-chain fatty acids, and four non-traditional circulating CV-related biomarkers. We found two major types of FAHFAs in healthy human circulation, palmitoleic acid ester of 9-hydroxystearic acid (9-POHSA), and oleic acid ester of 9-hydroxystearic acid (9-OAHSA). Both 9-POHSA and 9-OAHSA had a strong positive correlation with each other and were negatively correlated with fasting blood glucose, S-adenosyl-l-homocysteine (SAH), and trimethylamine N-oxide (TMAO), but not with l-homocysteine. 9-POHSA was also positively correlated with l-carnitine. Moreover, we confirmed that both 9-POHSA and 9-OAHSA exhibited an anti-inflammatory effect by suppressing LPS stimulated cytokines, including IL-1ß and IL-6 in RAW 264.7 cells. In addition, palmitoleic acid also had a positive correlation with 9-POHSA and 9-OAHSA. As far as we know, this is the first report showing the major endogenous FAHFAs in healthy subjects and their CV protection potential which might be correlated with SAH and TMAO reduction, l-Carnitine elevation, and their anti-inflammatory effects.

Serum indoxyl sulfate as a potential biomarker of aortic arterial stiffness in coronary artery disease.

BACKGROUND AND AIMS: Indoxyl sulfate (IS), a dietary tryptophan metabolite, acts as a cardiotoxin and uremic toxin. High IS levels are associated with chronic kidney disease and cardiovascular diseases. This study investigated the association between serum IS levels and aortic arterial stiffness (AAS) in coronary artery disease (CAD) patients. METHODS AND RESULTS: The carotid-femoral pulse wave velocity (cfPWV) was measured by the SphygmoCor system and patients with values of >10 m/s were classified in the AAS group. The baseline characteristics were recorded and measured (including biochemical and clinical data). Serum IS levels were determined using liquid chromatography-mass spectrometry. AAS occurred in 50 (34.7%) of 144 patients with CAD. They were older, had higher IS levels and percentages of diabetes, systolic blood pressure, blood urea nitrogen, and creatinine but lower estimated glomerular filtration rates. The IS level and older age significantly correlated with AAS [odds ratio (OR) = 3.834, p = 0.031; OR = 1.095, p = 0.002, respectively]. Furthermore, the serum IS level (ß = 0.167, adjusted R2 change: 0.026, p = 0.027) had a significant positive correlation with cfPWV. CONCLUSIONS: Taken together, higher serum IS levels are potential independent biomarkers for AAS in patients with CAD. Therefore, early checking of serum IS levels may help prevent CAD progression and have clinical implications in the near future.

Low Serum 3-Methylhistidine Levels Are Associated With First Hospitalization in Kidney Transplantation Recipients.

BACKGROUND: Low protein intake and increased muscle breakdown are associated with increased mortality risk in patients with kidney transplantation (KT). 3-methylhistidine (3-MH), a nonproteinogenic amino acid residue, is an index of muscle breakdown. the present study investigated the association between serum 3-MH levels and subsequent first hospitalization events in patients with KT. METHODS: A total of 64 KT patients were enrolled and 43 first hospitalization events occurred. Fasting blood samples were obtained and serum 3-MH level was performed with high-performance liquid chromatography and mass spectrometry. Associations between serum 3-MH levels and first hospitalization over a 5-year follow-up period were examined. RESULTS: Compared with patients without hospitalization, the 64 patients with KT revealed higher diabetes (P = .012) and hypertension (P = .006) prevalence, higher body fat mass (P = .012) and systolic blood pressure (P = .002), higher serum blood urea nitrogen (BUN) levels (P = .003), and lower serum 3-MH levels (P = .001). Statistical analysis revealed that serum 3-MH (95% confidence interval [CI]: 0.902-0.986, P = .010) and serum BUN (95% CI: 1.003-1.040, P = .022) levels were independently associated with first hospitalization events in patients with KT. Kaplan-Meier analysis showed a greater cumulative incidence of first hospitalization events in the patients with lower 3-MH levels (≤5.91 ng/mL) than that in those with higher 3-MH levels (P = .014; log-rank test). CONCLUSIONS: Low serum 3-MH levels are associated with increased first hospitalization risk in KT recipients.

Anti-Proliferative Effect of Statins Is Mediated by DNMT1 Inhibition and p21 Expression in OSCC Cells.

Statins, also known as HMG-CoA reductase inhibitors, are a class of cholesterol-lowering drugs and their anti-cancer effects have been studied in different types of malignant diseases. In the present study, we investigated the anti-proliferative effects of statins, including cerivastatin and simvastatin, on oral squamous cell carcinoma (OSCC) cells. Our data showed that statins inhibited the proliferation of three OSCC cell lines in a dose-dependent manner and this growth inhibition was confirmed through G0/G1 cell cycle arrest. Accordingly, we found the upregulation of p21 and downregulation of cyclin-dependent kinases, including CDK2, CDK4, and CDK6, in the statin-treated cells. Importantly, we clearly showed that statins were able to inhibit the expression of DNA methyltransferase 1 (DNMT1) and further promote the expression of p21. Taken together, our data demonstrated that the anti-proliferative effect of statins is mediated by suppressing DNMT1 expression, thus promoting p21 expression and leading to G0/G1 cell cycle arrest in OSCC cells.

Association of Serum Indoxyl Sulfate Levels with Skeletal Muscle Mass and Strength in Chronic Hemodialysis Patients: A 2-year Longitudinal Analysis.

Sarcopenia is highly prevalent in patients undergoing chronic hemodialysis (HD). This study investigated the relationship among serum indoxyl sulfate (IS) levels, muscle mass, and strength in HD patients. A total of 108 HD patients were enrolled. Skeletal muscle mass and handgrip strength (HGS) were assessed, using bioimpedance analysis and a hand-held dynamometer, respectively. Skeletal muscle index (SMI) was defined as skeletal muscle mass/height2 (kg/m2). Serum IS, p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO) levels were determined using liquid chromatography-mass spectrometry. Patients were classified into two groups based on median serum IS values. HGS measurement was repeated after 2 years. Patients in the high IS group had longer HD duration and higher serum TMAO levels than those in the low IS group. Log-normalized IS level was negatively correlated with SMI (r = - 0.227; p = 0.018), but PCS and TMAO levels were not. Among 78 patients who completed 2-year follow-up, those in the high IS group (n = 41) showed greater absolute (- 2.48 kg versus - 0.25 kg, p = 0.035) and relative HGS loss (- 9.1% versus 1.4%, p = 0.036) than those in the low IS group, after adjustment for potential confounders. Indoxyl sulfate (IS) may play a significant role in uremic sarcopenia. Further large-scale studies are needed to confirm our preliminary findings.

Eating right for a healthier heart: Food choice contributes to cardiometabolic benefits and reduction of carotid intima-media thickness.

OBJECTIVES: Diets may alter an individual's metabolism and inflammation, collectively leading to the modulation of cardiovascular health and disease process. The aim of this study was to investigate the effects of diets and diet-associated metabolites on metabolic profiles, inflammatory status, and severity of atherosclerosis. METHODS: A cross-sectional study was conducted with 81 healthy adults in Taiwan. A food frequency questionnaire was obtained for evaluating dietary intake. Carotid intima-media thickness (CIMT), a relevant marker of subclinical atherosclerosis, was measured by ultrasound. RESULTS: Consumption of instant noodles and sugary beverages was associated with worse metabolic profiles. In contrast, the intake of fresh fruit and green vegetables was correlated with better metabolic parameters. Sugary beverages were dose-dependently correlated with higher expressions of toll-like receptor (TLR)2 and TLR4 on monocytes, whereas fresh fruit intake was associated with lower TLRs. Furthermore, consumption of green vegetables, brown rice, and >2000 mL/d of water was inversely correlated with CIMT. The diet-associated metabolites including trimethylamine N-oxide and S-adenosyl-l-homocysteine, were positively associated with CIMT, whereas l-lysine and l-carnitine were associated with decreased CIMT. Interestingly, intake of strict vegetarian foods resulted in lower serum total cholesterol levels without a detectable effect on inflammatory status or CIMT. CONCLUSIONS: Independent of the pattern of strict vegetarian foods, individuals who consumed more vegetables, fresh fruit, and water showed better cardiovascular health as evidenced by their metabolic and inflammatory status and CIMT results.

Stearic acid methyl ester affords neuroprotection and improves functional outcomes after cardiac arrest.

Cardiac arrest causes neuronal damage and functional impairments that can result in learning/memory dysfunction after ischemia. We previously identified a saturated fatty acid (stearic acid methyl ester, SAME) that was released from the superior cervical ganglion (sympathetic ganglion). The function of stearic acid methyl ester is currently unknown. Here, we show that SAME can inhibit the detrimental effects of global cerebral ischemia (i.e. cardiac arrest). Treatment with SAME in the presence of asphyxial cardiac arrest (ACA) revived learning and working memory deficits. Similarly, SAME-treated hippocampal slices after oxygen-glucose deprivation inhibited neuronal cell death. Moreover, SAME afforded neuroprotection against ACA in the CA1 region of the hippocampus, reduced ionized calcium-binding adapter molecule 1 expression and inflammatory cytokines/chemokines, with restoration in mitochondria respiration. Altogether, we describe a unique and uncharted role of saturated fatty acids in the brain that may have important implications against cerebral ischemia.

COMT-Catalyzed Palmitic Acid Methyl Ester Biosynthesis in Perivascular Adipose Tissue and its Potential Role Against Hypertension.

Decreased release of palmitic acid methyl ester (PAME), a vasodilator, from perivascular adipose tissue (PVAT) might contribute to hypertension pathogenesis. However, the PAME biosynthetic pathway remains unclear. In this study, we hypothesized that PAME is biosynthesized from palmitic acid (PA) via human catechol-O-methyltransferase (COMT) catalysis and that decreased PAME biosynthesis plays a role in hypertension pathogenesis. We compared PAME biosynthesis between age-matched normotensive Wistar Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHRs) and investigated the effects of losartan treatment on PAME biosynthesis. Computational molecular modeling indicated that PA binds well at the active site of COMT. Furthermore, in in vitro enzymatic assays in the presence of COMT and S-5'-adenosyl-L-methionine (AdoMet), the stable isotope [13C16]-PA was methylated to form [13C16]-PAME in incubation medium or the Krebs-Henseleit solution containing 3T3-L1 adipocytes or rat PVAT. The adipocytes and PVATs expressed membrane-bound (MB)-COMT and soluble (S)-COMT proteins. [13C16]-PA methylation to form [13C16]-PAME in 3T3-L1 adipocytes and rat PVAT was blocked by various COMT inhibitors, such as S-(5'-adenosyl)-L-homocysteine, adenosine-2',3'-dialdehyde, and tolcapone. MB- and S-COMT levels in PVATs of established SHRs were significantly lower than those in PVATs of age-matched normotensive WKY rats, with decreased [13C16]-PA methylation to form [13C16]-PAME. This decrease was reversed by losartan, an angiotensin II (Ang II) type 1 receptor antagonist. Therefore, PAME biosynthesis in rat PVAT is dependent on AdoMet, catalyzed by COMT, and decreased in SHRs, further supporting the role of PVAT/PAME in hypertension pathogenesis. Moreover, the antihypertensive effect of losartan might be due partly to its increased PAME biosynthesis. SIGNIFICANCE STATEMENT: PAME is a key PVAT-derived relaxing factor. We for the first time demonstrate that PAME is synthesized through PA methylation via the S-5'-adenosyl-L-methionine-dependent COMT catalyzation pathway. Moreover, we confirmed PVAT dysfunction in the hypertensive state. COMT-dependent PAME biosynthesis is involved in Ang II receptor type 1-mediated blood pressure regulation, as evidenced by the reversal of decreased PAME biosynthesis in PVAT by losartan in hypertensive rats. This finding might help in developing novel therapeutic or preventive strategies against hypertension.

Palmitic Acid Methyl Ester Induces G2/M Arrest in Human Bone Marrow-Derived Mesenchymal Stem Cells via the p53/p21 Pathway.

Bone marrow-derived mesenchymal cells (BM-MSCs) are able to differentiate into adipocytes, which can secrete adipokines to affect BM-MSC proliferation and differentiation. Recent evidences indicated that adipocytes can secrete fatty acid metabolites, such as palmitic acid methyl ester (PAME), which is able to cause vasorelaxation and exerts anti-inflammatory effects. However, effects of PAME on BM-MSC proliferation remain unclear. The aim of this study was to investigate the effect of PAME on human BM-MSC (hBM-MSC) proliferation and its underlying molecular mechanisms. hBM-MSCs were treated with PAME for 48 h and then subjected to various analyses. The results from the present study show that PAME significantly reduced the levels of G2/M phase regulatory proteins, cyclin-dependent kinase 1 (Cdk1), and cyclin B1 and inhibited proliferation in hBM-MSCs. Moreover, the level of Mdm2 protein decreased, while the levels of p21 and p53 protein increased in the PAME-treated hBM-MSCs. However, PAME treatment did not significantly affect apoptosis/necrosis, ROS generation, and the level of Cdc25C protein. PAME also induced intracellular acidosis and increased intracellular Ca2+ levels. Cotreatment with PAME and Na+/H+ exchanger inhibitors together further reduced the intracellular pH but did not affect the PAME-induced decreases of cell proliferation and increases of the cell population at the G2/M phase. Cotreatment with PAME and a calcium chelator together inhibited the PAME-increased intracellular Ca2+ levels but did not affect the PAME-induced cell proliferation inhibition and G2/M cell cycle arrest. Moreover, the half-life of p53 protein was prolonged in the PAME-treated hBM-MSCs. Taken together, these results suggest that PAME induced p53 stabilization, which in turn increased the levels of p53/p21 proteins and decreased the levels of Cdk1/cyclin B1 proteins, thereby preventing the activation of Cdk1, and eventually caused cell cycle arrest at the G2/M phase. The findings from the present study might help get insight into the physiological roles of PAME in regulating hBM-MSC proliferation.

Association of Low Serum l-Carnitine Levels with Peripheral Arterial Stiffness in Patients Who Undergo Kidney Transplantation.

l-carnitine is an important co-factor in fatty-acid metabolism, and its deficiency is associated with insulin resistance, which is independently associated with arterial stiffness. This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). Fasting blood samples were collected from 65 patients who underwent KT. We measured the brachial-ankle pulse wave velocity, and 36 patients (55.4%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044); higher waist circumference (p = 0.010), systolic blood pressure (p = 0.002), serum triglyceride level (p = 0.040), insulin level (p = 0.002), and homeostasis model assessment of insulin resistance (p = 0.002); lower high-density lipoprotein cholesterol (p = 0.036) and serum l-carnitine levels (p < 0.001); older age (p = 0.041); and a longer KT duration (p = 0.025) than those without PAS. Statistical analysis revealed an independent association between PAS in KT and KT duration (95% confidence interval (CI): 1.003-1.054, p = 0.029) and serum l-carnitine levels (95% CI: 0.842-0.998, p = 0.044). The area under the receiver operating characteristic curve indicated that the diagnostic power of l-carnitine to predict PAS was 0.789 (95% CI: 0.670-0.881, p < 0.001). Serum-free l-carnitine level is negatively associated with PAS in patients who undergo KT.

A comparison of L-carnitine and several cardiovascular-related biomarkers between healthy vegetarians and omnivores.

OBJECTIVE: A plant-based diet has been associated with a reduced risk of cardiovascular (CV) diseases. This study aimed to determine the levels and correlations of CV-related biomarkers and the beneficial role of dietary habits. METHODS: A total of 63 healthy vegetarians (n = 32) and omnivores (n = 31) were recruited. The baseline characteristics were recorded and measured (including lipid profiles, blood glucose, etc.). Liquid chromatography-mass spectrometry method was developed for the simultaneous determination of seven circulating CV-related biomarkers. RESULTS: L-carnitine (L-Car), L-methionine, and ascorbic acid (AA) were significantly higher in vegetarians than in omnivores. In the vegetarians, L-Car had a negative correlation with triacylglycerols (P = 0.042) and blood glucose (P = 0.048) and a positive correlation with high-density lipoprotein cholesterol (P = 0.049). L-Car was also positively correlated with L-lysine (P = 0.009), L-methionine (P = 0.006), and AA (P = 0.035). The vegetarians' AA also had a negative correlation with L-homocysteine (P = 0.028). In the omnivores, L-Car was negatively correlated with total cholesterol (P = 0.008), low-density lipoprotein cholesterol (P = 0.004), and high-density lipoprotein cholesterol (P = 0.038). Omnivores' body mass index was positively correlated with L-homocysteine (P = 0.033), and age was positively correlated with trimethylamine N-oxide (P < 0.001) and blood glucose (P = 0.007), but not in vegetarians. CONCLUSIONS: Our results suggest that vegetarians have an elevated level of L-Car, which might be associated with endogenous biosynthesis and diet composition. Circulating L-Car might play an important role in CV protection, especially in vegetarians.

Glycolic acid attenuates UVB-induced aquaporin-3, matrix metalloproteinase-9 expression, and collagen degradation in keratinocytes and mouse skin.

Ultraviolet-B exposure causes an inflammatory response, photoaged skin, and degradation of extracellular matrix proteins including collagen and elastin. The regulation of these genes was suggested as an important mechanism to attenuate skin aging. Glycolic acid (GA) is commonly present in fruits and recently used to treat dermatological diseases. We reported that GA slows down cell inflammation and aging caused by UVB. Little is known about GA retarding the skin premature senescence or how to impede these events. To investigate the potential of GA to regulate the expression of MMPs and collagen, GA was topically applied onto human keratinocytes and the C57BL/6J mice dorsal skin. In the present study, we demonstrated that GA reduced UVB-induced type-I procollagen expression and secretory collagen levels. GA reverted and dose-dependently increased the level of aquaporin-3 (AQP3), the expression of which was down-regulated by UVB. The UV-induced MMP-9 level and activity were reduced by GA pre-treatment. Concomitantly, GA reverted mitogen-activated protein kinase (MMP-9) activation and inhibited the extracellular signal-regulated kinase activation (p38, pERK) triggered by UVB. The animal model also presented that GA attenuated the wrinkles caused by UVB on the mouse dorsal skin. Finally, GA triggers the transient receptor potential vanilloid-1 (TRPV-1) channel to initiate the anti-photoaging mechanism in keratinocytes. These findings clearly indicated that the mechanisms of GA promote skin protection against UVB-induced photoaging and wrinkle formation. GA might be an important reagent and more widely used to prevent UVB-induced skin aging.

Synergistic structures from magnetic freeze casting with surface magnetized alumina particles and platelets.

Magnetic freeze casting utilizes the freezing of water, a low magnetic field and surface magnetized materials to make multi-axis strengthened porous scaffolds. A much greater magnetic moment was measured for larger magnetized alumina platelets compared with smaller particles, which indicated that more platelet aggregation occurred within slurries. This led to more lamellar wall alignment along the magnetic field direction during magnetic freeze casting at 75 mT. Slurries with varying ratios of magnetized particles to platelets (0:1, 1:3, 1:1, 3:1, 7:1, 1:0) produced porous scaffolds with different structural features and degrees of lamellar wall alignment. The greatest mechanical enhancement in the magnetic field direction was identified in the synergistic condition with the highest particle to platelet ratio (7:1). Magnetic freeze casting with varying ratios of magnetized anisotropic and isotropic alumina provided insights about how heterogeneous morphologies aggregate within lamellar walls that impact mechanical properties. Fabrication of strengthened scaffolds with multi-axis aligned porosity was achieved without introducing different solid materials, freezing agents or additives. Resemblance of 7:1 particle to platelet scaffold microstructure to wood light-frame house construction is framed in the context of assembly inspiration being derived from both natural and synthetic sources.

Stiff, porous scaffolds from magnetized alumina particles aligned by magnetic freeze casting.

Bone consists of a hard mineral phase and a compliant biopolymer phase resulting in a composite material that is both lightweight and strong. Osteoporosis that degrades spongy bone preferentially over time leads to bone brittleness in the elderly. A porous ceramic material that can mimic spongy bone for a one-time implant provides a potential solution for the future needs of an aging population. Scaffolds made by magnetic freeze casting resemble the aligned porosity of spongy bone. A magnetic field applied throughout freezing induces particle chaining and alignment of lamellae structures between growing ice crystals. After freeze drying to extract the ice and sintering to strengthen the scaffold, cubes from the scaffold center are mechanically compressed along longitudinal (z-axis, ice growth direction) and transverse (y-axis, magnetic field direction) axes. The best alignment of lamellar walls in the scaffold center occurs when applying magnetic freeze casting with the largest particles (350nm) at an intermediate magnetic field strength (75mT), which also agrees with stiffness enhancement results in both z and y-axes. Magnetic moments of different sized magnetized alumina particles help determine the ideal magnetic field strength needed to induce alignment in the scaffold center rather than just at the poles.