Concentrations Of Chenodeoxycholic Acid Research Articles

Multiomics integration identifies regulatory factors underlying reproductive disorders in geese1

Geese, descendants of migratory birds, have preserved the distinct reproductive and lipid metabolism traits of their wild ancestors. Therefore, compared to other poultry, geese have lower egg production ability and a more sensitive susceptibility to fatty liver. Recent research underscores the impact of lipid metabolism disorders on female reproductive health. In this context, we observed reproductive disorders (RD) and lipid metabolism anomalies in certain geese populations. This study systematically elucidated the differences between RD and normal geese at various levels, including genomics, transcriptomics, bile acid metabolomics, and microbiomics, revealing the crucial role of microorganisms. Our study provides a thorough examination of the ovarian anatomical, histological, and transcriptomic profiles between normal and RD geese. Genomic analyses pinpoint mutations in genes associated with bile acid metabolism, highlighting their potential role in RD pathogenesis. The genomic discoveries are substantiated by precise bile acid assays and ileum transcriptome analyses, which expose a significant disruption in bile acid absorption, activation of FXR, and an increase in serum chenodeoxycholic acid (CDCA) concentrations within RD geese. Notably, 16S rRNA sequencing uncovers significantly greater beta diversity in the ileum microbiota of RD geese as compared to the normal group. Both Wilcoxon rank sum test and LEfSe analyses highlighted a marked increase in Romboutsia abundance in RD geese. Experimental cultivation of microbiota with CDCA supplementation confirms the impact of CDCA on Romboutsia lituseburensis (R. lituseburensis) proliferation. Gavage experiments with R. lituseburensis elucidates its involvement in primary follicle reduction via immune-mediated pathways. Collectively, our multi-faceted analysis unravels the intricate involvement of Romboutsia in goose RD, offering insights from genetic, physiological, and microbial dimensions. Our findings not only deepen our understanding of the etiology of RD in geese but also suggest potential avenues for therapeutic interventions targeting bile acid metabolism and the modulation of specific microbiota components.

Multispecies probiotics complex improves bile acids and gut microbiota metabolism status in an in vitro fermentation model.

The consumption of probiotics has been extensively employed for the management or prevention of gastrointestinal disorders by modifying the gut microbiota and changing metabolites. Nevertheless, the probiotic-mediated regulation of host metabolism through the metabolism of bile acids (BAs) remains inadequately comprehended. The gut-liver axis has received more attention in recent years due to its association with BA metabolism. The objective of this research was to examine the changes in BAs and gut microbiota using an in vitro fermentation model. The metabolism and regulation of gut microbiota by commercial probiotics complex containing various species such as Lactobacillus, Bifidobacterium, and Streptococcus were investigated. The findings indicated that the probiotic strains had produced diverse metabolic profiles of BAs. The probiotics mixture demonstrated the greatest capacity for Bile salt hydrolase (BSH) deconjugation and 7α-dehydroxylation, leading to a significant elevation in the concentrations of Chenodeoxycholic acid, Deoxycholic acidcholic acid, and hyocholic acid in humans. In addition, the probiotic mixtures have the potential to regulate the microbiome of the human intestines, resulting in a reduction of isobutyric acid, isovaleric acid, hydrogen sulfide, and ammonia. The probiotics complex intervention group showed a significant increase in the quantities of Lactobacillus and Bifidobacterium strains, in comparison to the control group. Hence, the use of probiotics complex to alter gut bacteria and enhance the conversion of BAs could be a promising approach to mitigate metabolic disorders in individuals.

Transparent Near‐IR Dye‐Sensitized Solar Cells: Ultrafast Spectroscopy Reveals the Effects of Driving Force and Dye Aggregation

AbstractIn the context of developing transparent near‐IR absorbing dye‐sensitized solar cells, diketopyrrolopyrrole (DPP) cyanine dyes have recently emerged as an alternative to strongly aggregating linear cyanines. In our efforts to increase both the power conversion efficiency (PCE) and the average visible transmittance (AVT), a thienylated version, called TB202, that shows a red‐shifted absorption with respect to our champion dye TB207 was designed. However, the lower energy LUMO level of TB202 brings along a lower driving force (−ΔG) for carrier injection, which we recently identified as the main parameter limiting the PCE to 1.5 % in the best device conditions. In the present paper, we publish a detailed account of the effect of the de‐aggregating cheno‐deoxycholic acid (CDCA) for both TB207 and TB202. Both transient absorption (TAS) and fluorescence up‐conversion (FLUPS) data are presented, which allow to quantitively compare the effect of −ΔG and the CDCA concentration, in terms of the kinetic competition of ensemble averaged carrier injection and monomer‐to‐aggregate energy transfer (ET) rates. A comprehensive picture emerges on how ET is reduced by higher CDCA concentrations, leading in the best device conditions to injection efficiencies in the range of 65 % for TB207 and only 35 % for TB202.

Farnesoid X Receptor (FXR) Regulates mTORC1 Signaling and Autophagy by Inhibiting SESN2 Expression.

The mechanistic target of rapamycin complex 1 (mTORC1), as a link between nutrients and autophagy, senses many nutrients in the microenvironment. A growing body of recent literature describes the function of bile acids (BAs) as versatile signaling molecules, while it remains largely unclear whether mTORC1 can sense BAs and the mechanism has not been studied. After treating LO2 cells with indicated concentration of chenodeoxycholic acid (CDCA) and farnesoid X receptor (FXR) inhibitor/activator for 6h, it finds that CDCA and FXR significantly accelerate mTORC1 activation. The results of immunofluorescence indicate that CDCA and FXR inhibit cellular autophagy through activating mTORC1 pathway. In particular, these findings show that CDCA and FXR promote the lysosomal translocation and activation of mTORC1 in an amino acid-sensitive manner. Mechanistically, the transcriptomics data indicate that SESN2 is a checkpoint for mTORC1 lysosome translocation and activation induced by FXR, and knockdown SESN2 with siRNA suppresses the regulation of FXR on autophagy. These results indicate that FXR-induced decrease in SESN2 expression and activation of the mTORC1 pathway can control autophagy and be explored as potential therapeutic targets for enterohepatic and metabolic disorders.

Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia

Emerging evidence indicates that bile acids (BAs), which are signaling molecules that regulate metabolism and inflammation, appear to be dysregulated in schizophrenia (SZ). Further investigation is warranted to comprehensively characterize BA profiles in SZ. To address this, we analyzed serum BA profiles in 108 drug-free patients with SZ and in 108 healthy controls (HCs), divided into a discovery set (n = 119) and a validation set (n = 97), using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Forty serum BAs were detected and absolutely quantified using calibration curves. Global BA profiling showed differences in SZ and HC groups in both discovery and validation sets. The concentrations of chenodeoxycholic acid, ursodeoxycholic acid, 3β-chenodeoxycholic acid, 7-ketolithocholic acid, 3-dehydrocholic acid, total BAs, and unconjugated BAs were significantly lower in patients with SZ compared with HCs in the two sample sets. The BA deconjugation potentials by gut microbiota and the affinity index of the farnesoid X receptor (FXR) were notably decreased in SZ patients compared to those of HCs. Conjugated BAs and BA deconjugation potentials differed in SZ patients with first versus recurrent episodes, although similar BA profiles were observed in both groups. In addition, a panel of 8 BA variables acted as a potential auxiliary diagnostic biomarker in discriminating SZ patients from HCs, with area under the curve values for receiver operating characteristic curves of 0.758 and 0.732 and for precision-recall curves of 0.750 and 0.714 in the discovery and validation sets, respectively. This study has provided compelling evidence of comprehensive characteristics of circulating BA metabolism in patients with SZ and promoted a deeper understanding of the role of BAs in the pathophysiology of this disease, possibly via the gut microbiota-FXR signaling pathway.

Gut Microbiome-Linked Metabolites in the Pathobiology of Major Depression With or Without Anxiety—A Role for Bile Acids

BackgroundThe gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid acids that are synthesized in the liver from cholesterol and further processed by gut-bacterial enzymes, thus requiring both human and gut microbiome enzymatic processes in their metabolism. BAs participate in a range of important host functions such as lipid transport and metabolism, cellular signaling and regulation of energy homeostasis. BAs have recently been implicated in the pathophysiology of Alzheimer's and several other neuropsychiatric diseases, but the biochemical underpinnings of these gut microbiome-linked metabolites in the pathophysiology of depression and anxiety remains largely unknown.MethodUsing targeted metabolomics, we profiled primary and secondary BAs in the baseline serum samples of 208 untreated outpatients with MDD. We assessed the relationship of BA concentrations and the severity of depressive and anxiety symptoms as defined by the 17-item Hamilton Depression Rating Scale (HRSD17) and the 14-item Hamilton Anxiety Rating Scale (HRSA-Total), respectively. We also evaluated whether the baseline metabolic profile of BA informs about treatment outcomes.ResultsThe concentration of the primary BA chenodeoxycholic acid (CDCA) was significantly lower at baseline in both severely depressed (log2 fold difference (LFD) = −0.48; p = 0.021) and highly anxious (LFD = −0.43; p = 0.021) participants compared to participants with less severe symptoms. The gut bacteria-derived secondary BAs produced from CDCA such as lithocholic acid (LCA) and several of its metabolites, and their ratios to primary BAs, were significantly higher in the more anxious participants (LFD's range = [0.23, 1.36]; p's range = [6.85E-6, 1.86E-2]). The interaction analysis of HRSD17 and HRSA-Total suggested that the BA concentration differences were more strongly correlated to the symptoms of anxiety than depression. Significant differences in baseline CDCA (LFD = −0.87, p = 0.0009), isoLCA (LFD = −1.08, p = 0.016) and several BA ratios (LFD's range [0.46, 1.66], p's range [0.0003, 0.049]) differentiated treatment failures from remitters.ConclusionIn patients with MDD, BA profiles representing changes in gut microbiome compositions are associated with higher levels of anxiety and increased probability of first-line treatment failure. If confirmed, these findings suggest the possibility of developing gut microbiome-directed therapies for MDD characterized by gut dysbiosis.

Effect of chenodeoxycholic acid as dye co-adsorbent and ZnO blocking layer in improving the performance of Rose Bengal dye based dye sensitized solar cells

Effective suppression of dye aggregation on the photoanode surface of dye sensitized solar cells plays a key role in improving solar cell efficiency. Chenodeoxycholic acid (CDCA) is a very popular anti dye aggregation material used in dye sensitized solar cells (DSSC). However, the selection of an improper concentration of CDCA may lead to decreased solar cell efficiency by lowering the open circuit voltage and short circuit current as a consequence of reduced dye loading. The influence of CDCA as a dye co-adsorbent on the performance of DSSCs fabricated using Rose Bengal dye was studied in this paper. The concentration of the CDCA solution was varied to identify the optimum value for the best device performance. Aside from this, the effect of a very thin and compact ZnO blocking layer was also investigated to reduce the charge recombination. With photovoltaic parameters such as short circuit current density (Jsc) = 1.98 mA/cm2, open circuit voltage (Voc) = 0.58 V, and fill factor (FF) = 0.43, the traditional cell displayed an overall conversion efficiency of 0.49%, while the power conversion efficiency was found to be increased to 1.00% (Jsc = 2.80 mA/cm2, Voc = 0.64, FF = 0.58) when CDCA was added at optimised concentration of 8 mM. Reduced dye aggregation and increased electron injection in the presence of CDCA may be accounted for the DSSC's remarkable improvement in the efficiency. Moreover, the combined effect of 8 mM CDCA and the compact ZnO blocking layer dramatically enhanced the efficiency further to 1.22% (Jsc = 3.09 mA/cm2, Voc = 0.66, FF = 60). Electrochemical impedance spectroscopic (EIS) analysis revealed that the addition of CDCA as a co-adsorbent in the dye solution and addition of ZnO blocking layer resulted in significantly improved electron lifetime and reduced electron recombination yielding improved Jsc, Voc and η.

Beneficial Actions of Essential Fatty Acids in Streptozotocin-Induced Type 1 Diabetes Mellitus.

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)—derived from LA—in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 μg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.

Regional differences in bile acid composition in gallbladder bile

Background: Chemical and structural analyses of gallstones (GS) from the Indian subcontinent has shown that the formation of GS type is dependent on regional and dietary factors. Aim of the Study: The aim is to determine the proportion of primary and secondary bile acids in gallbladder (GB) bile in patients with GS from South and North India using high-performance liquid chromatography (HPLC). Materials and Methods: Standards for primary and secondary bile acids were prepared and concentrations were determined by reversed-phase C18 HPLC column. Thirty-three GB bile samples from southern India and 28 samples from northern states of India were analyzed for differences in the proportion of primary and secondary bile acids. Ethics Committee of Gleneagles Global Health City, Chennai, approved the study. Statistical Analysis: concentration of bile acids (in mmol/L) were expressed as median and range. Chi-square test and Mann–Whitney U-test were applied. A P < 0.05 was considered as significant. Results: The median concentrations of cholic acid (CA) (P = 0.005) and its derivative deoxycholic acid (DCA) (P < 0.006) were significantly high in GB bile samples from South India with no differences in the concentration of chenodeoxycholic acid between the two samples. Furthermore, samples from North India had a significantly higher proportion of lithocholic acid (LCA) and low DCA compared to samples from South India. Conclusion: Primary bile acid CA and its derivative is high in GB bile from South; the proportion of hepatotoxic LCA is significantly high with low concentrations of DCA in bile samples from North India.

Influence of the concentration of chenodeoxycholic acid on the performance of the N719 dye

The influence of the Chenodeoxycholic acid (CDCA) at different concentrations on the spectroscopic and photovoltaic performances of the N719 dye was determined. Absorption analyses revealed the excellent capacity of the CDCA in stabilizing the N719 dye. The N719 dye exhibited hydroxyl and carboxylic functional groups that were accountable for the strong interactions and fast transport of electrons to the TiO2 surface. The photoluminescence emission spectroscopy of the CDCA-incorporated dye exhibited the feasibility of a large photocurrent generation. The interaction mechanism of CDCA within the N719 dye influenced the efficiency of the fabricated cell because the high photoconversion efficiency of 4.07% was recorded for 0 mM CDCA. This finding was because CDCA decreased the electrolyte contact with the N719 dye, resulting in charge accumulation in the electrolyte and decreased electron density in the N719 dye. Present findings are beneficial for the development of efficient dye-based DSSCs.

Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways.

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

Bile Acid Profiles in Primary Sclerosing Cholangitis and Their Ability to Predict Hepatic Decompensation.

Altered bile acid (BA) homeostasis is an intrinsic facet of cholestatic liver diseases, but clinical usefulness of plasma BA assessment in primary sclerosing cholangitis (PSC) remains understudied. We performed BA profiling in a large retrospective cohort of patients with PSC and matched healthy controls, hypothesizing that plasma BA profiles vary among patients and have clinical utility. Plasma BA profiling was performed in the Clinical Biochemical Genetics Laboratory at Mayo Clinic using a mass spectrometry based assay. Cox proportional hazard (univariate) and gradient boosting machines (multivariable) models were used to evaluate whether BA variables predict 5-year risk of hepatic decompensation (HD; defined as ascites, variceal hemorrhage, or encephalopathy). There were 400 patients with PSC and 302 controls in the derivation cohort (Mayo Clinic) and 108 patients with PSC in the validation cohort (Norwegian PSC Research Center). Patients with PSC had increased BA levels, conjugated fraction, and primary-to-secondary BA ratios relative to controls. Ursodeoxycholic acid (UDCA) increased total plasma BA level while lowering cholic acid and chenodeoxycholic acid concentrations. Patients without inflammatory bowel disease (IBD) had primary-to-secondary BA ratios between those of controls and patients with ulcerative colitis. HD risk was associated with increased concentration and conjugated fraction of many BA, whereas higher G:T conjugation ratios were protective. The machine-learning model, PSC-BA profile score (concordance statistic [C-statistic], 0.95), predicted HD better than individual measures, including alkaline phosphatase, and performed well in validation (C-statistic, 0.86). Patients with PSC demonstrated alterations of plasma BA consistent with known mechanisms of cholestasis, UDCA treatment, and IBD. Notably, BA profiles predicted future HD, establishing the clinical potential of BA profiling, which may be suited for use in clinical trials.

Bile acids LCA and CDCA inhibited porcine deltacoronavirus replication in vitro

Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes gastroenteritis in pigs and no vaccines or antiviral drugs are available. Bile acids are active factors in intestines and influence the replication of enteric viruses. Currently, the role of bile acids on PDCoV replication is unknown. In this study, we tested the effects of different types of bile acids on the replication of PDCoV in cell culture. We found that physiological concentrations of bile acids chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) had antiviral activity against PDCoV in porcine kidney cell line (LLC-PK1) and porcine small intestinal epithelial cell line (IPEC-J2). In IPEC-J2 cells, CDCA and LCA inhibited PDCoV replication at post-entry stages by inducing the production of interferon (IFN)-λ3 and IFN-stimulated gene 15 (ISG15) via G protein-coupled receptor (GPCR). In summary, bile acids CDCA and LCA restricted PDCoV infection and LCA functioned through a GPCR-IFN-λ3-ISG15 signaling axis in IPEC-J2 cells. Our results may open new avenues for the development of antiviral drugs to treat PDCoV infection in pigs.

Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages.

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.

Abstract PS6-59: Impact of Cholecystectomy in Breast Cancer Recurrence

Abstract Background: Several published studies demonstrate that bile acid metabolites may influence the growth of breast cancer cells in vitro. Our group has shown reduced plasma concentrations of cholic acid and chenodeoxycholic acid (primary bile acids) and deoxycholic acid and lithocholic acid (secondary bile acids) in breast cancer patients that later on develop tumor recurrence. Cholecystectomy reduces the circulating bile acid pool. In patients with prior cholecystectomy, changes in bile acid metabolites may contribute to breast cancer tumorigenesis and recurrence. This study investigates our institutional rate of cholecystectomy in women diagnosed with breast cancer and its impact on breast cancer recurrence. Methods: A retrospective review of patients with an invasive breast cancer diagnosis between 2014-2015 was conducted. Demographics, preoperative variables, surgical history and clinical outcome data was collected. 5-year disease-free survival (DFS) was compared using a Log-rank (Mantel-Cox) test. Results: The study included 264 patients with mean age of 60.9. Most were Caucasian (83.5%). The majority were diagnosed at Stage II or lower (80.3%) and had hormone receptor positive, HER2 negative breast cancer (72.9%). Approximately 22.7% of patients had prior cholecystectomy surgery. The only statistically significant heterogeneity in demographic data between patients with and without cholecystectomy was body mass index (BMI). Patients with cholecystectomy had a mean BMI of 33.3, versus 29.1 in patients with intact gallbladders. The 5-year DFS in breast cancer patients with cholecystectomy was 91.6%, versus 97.1% in patients with intact gallbladders (p=0.06). Conclusion: Women with breast cancer who had a history of cholecystectomy had increased rates of breast cancer recurrence over a 5-year period compared to women with breast cancer with intact gallbladders. Although this result was not statistically significant, a trend was seen. Future study of a larger patient sample size sample may lead to a statistical significant difference. The statistically significant difference in BMI between the two patient groups is likely a confounding factor, given increased BMI is a known risk factor for developing cholecystitis and breast cancer. This data supports existing in vitro studies that bile acids may influence the growth of breast cancer cells. There may be utility in closer follow-up of women with breast cancer and a history of cholecystectomy given the increased rate of breast cancer recurrence in this population. Citation Format: Isheeta Madeka, Rohin Gawdi, Katherine L Cook, Akiko Chiba. Impact of Cholecystectomy in Breast Cancer Recurrence [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-59.

Interfacial defect passivation by chenodeoxycholic acid for efficient and stable perovskite solar cells

Passivating the surface defects of perovskite has become one of the important strategies to suppress non-radiative recombination and improve the photovoltaic performance and stability of perovskite solar cells (PVSCs). Herein, we introduce chenodeoxycholic acid (CDCA) on the surface of perovskite layer. The infrared spectra and nuclear magnetic resonance (1H NMR) spectra prove the carboxyl (–COOH) group on CDCA combination with the formamidinium (FA+) ions on perovskite. The water-contact angle measurement indicates that the long alkyl chain of CDCA covers the surface of perovskite film. The photoelectrical characterization demonstrates that the surface defects of the perovskite layer are passivated and carrier non-radiative combinations are suppressed. Under an optimized CDCA concentration of 0.2 mg⋅ml−1, the CDCA passivated PVSC achieves an average power conversion efficiency (PCE) of 20.41%, as compared with the pristine PVSC with an average PCE of 18.18%.

Areca catechu extracted natural new sensitizer for dye-sensitized solar cell: performance evaluation

This paper reports the optical and photovoltaic traits of a new type of natural organic dye sensitizer derived from the Malaysian Areca catechu (Pinang) fruit. The photovoltaic potential of this dye was determined by fabricating a dye-sensitized solar cell (DSSC). In this work, the effects of various concentrations of chenodeoxycholic acid (CDCA) and solvent types on the photovoltaic efficiency of this dye were evaluated. Methanol was the best solvent, obtaining the highest absorbance from natural dye. The absorption analyses showed the excellent dye-stabilizing capacity of CDCA. The Fourier-transform infrared spectra revealed the presence of hydroxyl and carboxylic functional groups in the extracted natural dye, which were shown to be responsible for imparting the stronger electronic coupling and rapid electron transfer upon interaction with the TiO2 surface. The photoluminescence spectral analyses of the dye showed that the inclusion of CDCA as a co-adsorbent can produce a large photocurrent through the narrowing of the band gap. Device performance was measured as a function of co-adsorbent content at the loading times of 0 and 30 min. The efficiency measured after adding CDCA and 30 min of loading time was 0.118%, with short-circuit current density (Jsc) = 0.3 mA/cm2, open circuit voltage (Voc) = 0.536 V, and fill factor (FF) = 73.5%. This short disclosure may contribute towards the development of a natural dye-based efficient DSSC.

Oral gavage of nano-encapsulated conjugated acrylic acid-bile acid formulation in type 1 diabetes altered pharmacological profile of bile acids, and improved glycaemia and suppressed inflammation.

Ursodeoxycholic acid (UDCA) is a secondary hydrophilic bile acid, metabolised in the gut, by microbiota. UDCA is currently prescribed for primary biliary cirrhosis, and of recently has shown β-cell protective effects, which suggests potential antidiabetic effects. Thus, this study aimed to design targeted-delivery microcapsules for oral uptake of UDCA and test its effects in type 1 diabetes (T1D). UDCA microcapsules were produced using alginate-NM30 matrix. Three equal groups of mice (6-7 mice per group) were gavaged daily UDCA powder, empty microcapsules and UDCA microcapsules for 7days, then T1D was induced by alloxan injection and treatments continued until mice had to be euthanised due to weight loss > 10% or severe symptoms develop. Plasma, tissues, and faeces were collected and analysed for bile acids' concentrations. UDCA microcapsules brought about reduction in elevated blood glucose, reduced inflammation and altered concentrations of the primary bile acid chenodeoxycholic acid and the secondary bile acid lithocholic acid, without affecting survival rate of mice. The findings suggest that UDCA exerted direct protective effects on pancreatic β-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues. Three equal groups of mice were gavaged daily UDCA (ursodeoxycholic acid) powder, empty microcapsules and UDCA microcapsules for 7days, then T1D was induced and treatments continued until mice had to be euthanised. UDCA microcapsules brought about reduction in elevated blood glucose, reduced inflammation and altered concentrations of the primary bile acid chenodeoxycholic acid and the secondary bile acid lithocholic acid, without affecting survival rate of mice. The findings suggest that UDCA exerted direct protective effects on pancreatic β-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues.

Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition

The bile acid (BA) composition in mice is substantially different from that in humans. Chenodeoxycholic acid (CDCA) is an end product in the human liver; however, mouse Cyp2c70 metabolizes CDCA to hydrophilic muricholic acids (MCAs). Moreover, in humans, the gut microbiota converts the primary BAs, cholic acid and CDCA, into deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. In contrast, the mouse Cyp2a12 reverts this action and converts these secondary BAs to primary BAs. Here, we generated Cyp2a12 KO, Cyp2c70 KO, and Cyp2a12/Cyp2c70 double KO (DKO) mice using the CRISPR-Cas9 system to study the regulation of BA metabolism under hydrophobic BA composition. Cyp2a12 KO mice showed the accumulation of DCAs, whereas Cyp2c70 KO mice lacked MCAs and exhibited markedly increased hepatobiliary proportions of CDCA. In DKO mice, not only DCAs or CDCAs but also DCAs, CDCAs, and LCAs were all elevated. In Cyp2c70 KO and DKO mice, chronic liver inflammation was observed depending on the hepatic unconjugated CDCA concentrations. The BA pool was markedly reduced in Cyp2c70 KO and DKO mice, but the FXR was not activated. It was suggested that the cytokine/c-Jun N-terminal kinase signaling pathway and the pregnane X receptor-mediated pathway are the predominant mechanisms, preferred over the FXR/small heterodimer partner and FXR/fibroblast growth factor 15 pathways, for controlling BA synthesis under hydrophobic BA composition. From our results, we hypothesize that these KO mice can be novel and useful models for investigating the roles of hydrophobic BAs in various human diseases.

Postprandial Responses of Serum Bile Acids in Healthy Humans after Ingestion of Turmeric before Medium/High-Fat Breakfasts.

Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aims to investigate whether a single dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects. Twelve healthy subjects are assigned to a randomized crossover single-blind study. The subjects receive isocaloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least 1-week wash-out period between the treatments. Postprandial BAs are measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis. The concentration of BAs is generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increases the serum concentrations of free and conjugated forms of cholic (CA) and ursodeoxycholic acids (UDCA), as well as the concentrations of chenodeoxycholic acid (CDCA) and its taurine-conjugated forms. However, the concentration of conjugated forms of deoxycholic acid (DCA) decreases when TUR is taken before HF breakfast. TUR ingestion before MF and HF breakfasts improve BA profiles and may therefore have potential health-promoting effects on BA metabolism.