Ursodeoxycholic Acid Research Articles

Measuring bile acids: Are we all talking the same language?

In this paper, we discuss the Bile Acid Comparison and Harmonisation project, a sub-study of the Trial of URsodeoxycholic acid vs RIFampicin in early-onset severe Intrahepatic Cholestasis of pregnancy, giving an overview of the current state of affairs for total bile acid measurements.

Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea

BackgroundConflicting evidence exists regarding the effects of ursodeoxycholic acid (UDCA) on coronavirus disease 2019 (COVID-19). This study investigates the association between UDCA administration and COVID-19 infection and its related outcomes in individuals with chronic liver disease (CLD).MethodsA customized COVID-19 research database (n = 3,485,376) was created by integrating data from the National Health Insurance Service (NHIS) and the Korea Disease Control and Prevention Agency’s COVID-19 databases. The study focused on patients diagnosed with COVID-19 in 2021, using the NHIS data from 365 days before diagnosis. To create comparable groups with and without UDCA administration before COVID-19, we used propensity score matching. The primary endpoint was the first confirmed positive result for severe acute respiratory syndrome coronavirus-2. In addition, we identified severe COVID-19-related outcomes. Subgroup analysis were conducted based on the dose of UDCA exposure.ResultsData from 74,074 individuals with CLD was analyzed. The participants’ average age was 57.5 years, and 52.1% (19,277) of those in each group were male. Those with prior UDCA exposure had a significantly lower risk of COVID-19 infection (adjusted OR: 0.80, 95% CI [0.76–0.85]) compared to the non-UDCA group. Additionally, the UDCA group had a lower risk of severe COVID-19 outcomes (adjusted OR: 0.67, 95% CI [0.46–0.98]). Subgroup analyses indicated that there was a decrease in COVID-19 infection and its related outcomes with increasing UDCA exposure dose.ConclusionsOur large observational study highlights the potential use of readily available UDCA as an adjunctive therapy for COVID-19 in individuals with CLD.

Unresolved alterations in bile acid composition and dyslipidemia in maternal and cord blood after ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy.

This study uncovers that despite ursodeoxycholic acid treatment, intrahepatic cholestasis of pregnancy (ICP) is associated with increases in the ratio of cholic acid to chenodeoxycholic acid in both maternal and cord blood, suggesting ongoing dysregulation of bile acid metabolism. The high cholic to chenodeoxycholic acid ratio is correlated with maternal dyslipidemia and high cord blood lipids. These findings may inform more targeted approaches to managing ICP.

Alkaline phosphatase and liver fibrosis at diagnosis are associated with deep response to ursodeoxycholic acid in primary biliary cholangitis

ObjectivePrimary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40 % of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation. Patient and methodsData from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response, defined as normal alkaline phosphatase and bilirubin, after 1 year of UDCA treatment. Additionally, the performance of the UDCA response score in predicting deep response was evaluated. ResultsA total of 297 patients were analyzed, with 57.2 % achieving an adequate response according to the Toronto criteria, while 22.9 % reached deep response. Cirrhosis (OR 0.460; 95 % CI 0.225–0.942; p = 0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95 % CI 0.513–0.770; p < 0.001) were associated with reduced odds of deep response. The UDCA response score exhibited moderate discrimination power (AUROC = 0.769) but lacked calibration. ConclusionsBaseline ALP and liver fibrosis emerge as the most important prognostic factors to predict normalization of alkaline phosphatase and bilirubin after UDCA. The UDCA response score was inadequate for predicting deep response in the Brazilian PBC population.

Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice

ABSTRACT Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.

Evaluating Real-World Evidence of Effectiveness and Safety of Ursodeoxycholic Acid, Saroglitazar, and Vitamin E Monotherapies in Indian Patients with Non-Alcoholic Fatty Disease and Cholestasis: The ELITE Study

Evaluating Real-World Evidence of Effectiveness and Safety of Ursodeoxycholic Acid, Saroglitazar, and Vitamin E Monotherapies in Indian Patients with Non-Alcoholic Fatty Disease and Cholestasis: The ELITE Study

Effects of dietary protein level on liver lipid deposition, bile acid profile and gut microbiota composition of growing pullets

The current study investigated the effects of dietary crude protein (CP) level on the liver lipid metabolism, gut microbiota, and bile acids (BA) profiles of growing pullets. Roman growing pullets (N = 180, 13-wk-old) were divided into 3 treatments groups with 6 replicates in each group and 10 hens in each replicate and provided 3 different dietary CP level diet treatments. The diet treatments included: a high-protein diet (15.5% CP, HP group), a medium-protein diet (14.5% CP, MP group), and a low-protein diet (13.5% CP, LP group). Compared with HP group, LP group significantly increased the lipid contents in the body (such as Breast intramuscular fat [BIMF], Leg intramuscular fat [LIMF], Percentage of abdominal fat [PAF], liver triglyceride [TG] and liver cholesterol [TC]), and the lipid metabolism-related parameters in serum (such as cholesterol (TC), high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low density lipoprotein [VLDL]), and the mRNA expression of lipid metabolism-related genes (such as fatty acid synthase [FAS], CCAAT/enhancer binding protein β [C/EBPβ], and fatty acid translocase [FAT/CD6]) (P < 0.05). In addition, LP group significantly reduced the contents of lithocholic acid (LCA), isoLCA, and ursodesoxycholic acid (UDCA), and increased the deoxycholic acid (DCA) content compared with HP group (P < 0.05). The effects of LCA on lipid deposition were confirmed in chicken preadipocyte cell line (CPI), in which LCA supplementation significantly decreased the relative expression of PPARγ, FAS, acyl-CoA carboxylase (ACC) and SREBP-1c (P < 0.05). Correlation analysis further revealed a significant association between BA profiles and lipid metabolism-related parameters. Furthermore, 16S rRNA gene sequencing indicated that dietary protein level can significantly affect the richness, diversity, and composition of cecal microbiota in growing pullets. LP group significantly increased the abundance of Bacteroidetes and significantly decreased the abundance of Firmicutesa compared with the HP group. In summary, low protein diet in growing pullets influence the liver lipid metabolism through changing the gut microbiota and liver BA metabolism.

Biliary atresia with rare associations: a case report and literature review

Introduction and Importance: Biliary atresia is a rare, progressive cholangiopathy that affects newborns, causing jaundice and other manifestations of hyperbilirubinemia. The incidence is higher in Asia than in Europe. The only available treatment is a surgical operation called Kasai portoenterostomy. In our case, we highlighted rare congenital anomalies that came with biliary atresia. Case Presentation: A 10-day-old male infant was admitted to the hospital due to recurrent vomiting, yellowish skin, and scleral icterus. Laboratory investigations revealed elevated total serum and direct bilirubin levels. An atrophic gallbladder was observed on ultrasound. Intrahepatic cholangiography confirmed the diagnosis of biliary atresia, leading to the performance of a Kasai procedure. Additionally, the patient had intestinal malrotation and volvulus, which were managed with a Ladd’s procedure. Following surgery, there was notable improvement in liver enzymes and bilirubin levels, and the patient was discharged after 7 days. The infant has been initiated on oral vitamins, ursodeoxycholic acid, and antibiotics. Clinical Discussion: Biliary atresia is a challenging condition characterized by progressive narrowing and fibrosis of the biliary tree. It is rarely associated with rare congenital anomalies like situs inversus totalis, intestinal malrotation, and volvulus. Diagnosis involves abdominal ultrasound and MRCG. The biliary atresia was managed by the kasai procedure and the intestinal malrotation, and volvulus were managed by Ladd’s procedure. Conclusion: This case report highlights the importance of considering rare associations such as situs inversus, intestinal malrotation and volvulus in the diagnosis of biliary atresia in newborn. Early diagnosis and prompt intervention are crucial for optimal outcomes.

Elafibranor: First Approval.

Elafibranor (IQIRVO®) is a first-in-class peroxisome proliferator-activated receptor (PPAR) agonist being developed by Ipsen, under license from Genfit, for the treatment of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). On 10June 2024, elafibranor received accelerated approval based on reduction of alkaline phosphatase (ALP) in the USA for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Elafibranor has also received a positive opinion in the EU. This article summarizes the milestones in the development of elafibranor leading to this first approval for PBC.

Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

The External Validation of GLOBE and UK-PBC Risk Scores for Predicting Ursodeoxycholic Acid Treatment Response in a Large U.S. Cohort of Primary Biliary Cholangitis Patients.

Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p < 0.001). The area under the ROC curve was 0.87 (95% CI 0.83-0.95) for the GLOBE score and 0.94 (95% CI 0.86-0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies.

PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases.

Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), result from an impairment of bile flow that leads to the hepatic retention of bile acids, causing liver injury. Until recently, the only approved treatments for PBC were ursodeoxycholic acid (UDCA) and obeticholic acid (OCA). While these therapies slow the progression of PBC in the early stage of the disease, approximately 40% of patients respond incompletely to UDCA, and advanced cases do not respond. UDCA does not improve survival in patients with PSC, and patients often have dose-limiting pruritus reactions to OCA. Left untreated, these diseases can progress to fibrosis and cirrhosis, resulting in liver failure and the need for transplantation. These shortcomings emphasize the urgent need for alternative treatment strategies. Recently, nuclear hormone receptors have been explored as pharmacological targets for adjunct therapy because they regulate enzymes involved in bile acid metabolism and detoxification. In particular, the peroxisome proliferator-activated receptor (PPAR) has emerged as a therapeutic target for patients with PBC or PSC who experience an incomplete response to UDCA. PPARα is predominantly expressed in the liver, and it plays an essential role in the regulation of cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, both of which are critical enzyme families involved in the regulation of bile acid metabolism and glucuronidation, respectively. Importantly, PPARα agonists, e.g., fenofibrate, have shown therapeutic benefits in reducing elevated markers of cholestasis in patients with PBC and PSC, and elafibranor, the first PPAR (dual α, β/δ) agonist, has been FDA-approved for the second-line treatment of PBC. Additionally, newer PPAR agonists that target various PPAR isoforms (β/δ, γ) are under development as an adjunct therapy for PBC or PSC, although their impact on glucuronidation pathways are less characterized. This review will focus on PPAR-mediated bile acid glucuronidation as a therapeutic pathway to improve outcomes for patients with PBC and PSC.

In Vitro Studies to Evaluate the Intestinal Permeation of an Ursodeoxycholic Acid-Conjugated Oligonucleotide for Duchenne Muscular Dystrophy Treatment.

Delivery represents a major hurdle to the clinical advancement of oligonucleotide therapeutics for the treatment of disorders such as Duchenne muscular dystrophy (DMD). In this preliminary study, we explored the ability of 2'-O-methyl-phosphorothioate antisense oligonucleotides (ASOs) conjugated with lipophilic ursodeoxycholic acid (UDCA) to permeate across intestinal barriers in vitro by a co-culture system of non-contacting IEC-6 cells and DMD myotubes, either alone or encapsulated in exosomes. UDCA was used to enhance the lipophilicity and membrane permeability of ASOs, potentially improving oral bioavailability. Exosomes were employed due to their biocompatibility and ability to deliver therapeutic cargo across biological barriers. Exon skipping was evaluated in the DMD myotubes to reveal the targeting efficiency. Exosomes extracted from milk and wild-type myotubes loaded with 5'-UDC-3'Cy3-ASO and seeded directly on DMD myotubes appear able to fuse to myotubes and induce exon skipping, up to ~20%. Permeation studies using the co-culture system were performed with 5'-UDC-3'Cy3-ASO 51 alone or loaded in milk-derived exosomes. In this setting, only gymnotic delivery induced significant levels of exon skipping (almost 30%) implying a possible role of the intestinal cells in enhancing delivery of ASOs. These results warrant further investigations to elucidate the delivery of ASOs by gymnosis or exosomes.

Gallstones: Prevention, Diagnosis, and Treatment.

Gallstones are common and affect up to 20% of the general adult population and >20% of them will develop symptoms or complications of cholelithiasis. The high risk of gallbladder stone formation can be reduced by ursodeoxycholic acid in the case of significant weight reduction resulting from diet or bariatric surgery. Laparoscopic cholecystectomy is indicated for symptomatic gallstones, as the risk of recurrence or complications increases over the course of the disease. Biliary colic is treated with nonsteroidal anti-inflammatory drugs and spasmolytics; opioids can also be used in cases of severe acute pain. Acute cholecystitis represents a common complication of gallbladder stones and a cholecystectomy should be performed early electively, i.e., within 24 hours of admission to hospital. Symptomatic bile duct stones are primarily treated endoscopically. Immediate anti-infective therapy is mandatory in acute cholangitis. Although knowledge on the genetics and pathophysiology of gallstones has increased, current treatment algorithms remain predominantly invasive, based on interventional endoscopy and surgery. Future efforts should focus on novel strategies to prevent the development of gallstones.

Unsymmetric Chiral Ligands for Large Metallo‐Macrocycles: Selectivity of Orientational Self‐Sorting

AbstractNature uses various chiral and unsymmetric building blocks to form substantial and complex supramolecular assemblies. In contrast, the majority of organic ligands used in metallosupramolecular chemistry are symmetric and achiral. Here we extend the group of unsymmetric chiral bile acids used as a scaffold for organic bispyridyl ligands by employing chenodeoxycholic acid (CDCA), an epimer of the previously used ursodeoxycholic acid (UDCA). The epimerism, flexibility, and bulkiness of the ligands leads to large structural differences in coordination products upon reaction with Pd(NO3)2. The UDCA‐bispyridyl ligand self‐assembles quantitatively into a single crown‐like Pd3L6 complex, whereas the CDCA ligand provides a mixture of coordination complexes of general formula PdnL2n, i.e., Pd2L4, Pd3L6, Pd4L8, Pd5L10, and even Pd6L12 containing an impressive 120 chiral centers. The coordination products were studied by a combination of analytical methods, with ion‐mobility mass spectrometry (IM‐MS) providing valuable details on their structure and allowed an effective separation of m/z 1461 to individual signals according to the arrival time distribution, thereby revealing four different ions of [Pd3L6(NO3)3]3+, [Pd4L8(NO3)4]4+, [Pd5L10(NO3)5]5+, and [Pd6L12(NO3)6]6+. The structures of all the complexes were modelled using DFT calculations. Finally, the challenges and conclusions in determining the specific structural identity of these unsymmetric species are discussed.

Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid

BackgroundBile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA).ResultsHere, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo.ConclusionsThe distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

Unraveling the molecular regulation of biofilm underlying effect of chronic disease medications.

A biofilm is a complex microbial structure that promotes the progression of persistent infections, particularly in nosocomial settings via indwelling medical devices. Conventional antibiotics are often ineffective treatments for biofilms; hence, it is crucial to investigate or design non-antibiotic antibiofilm compounds that can successfully reduce and eradicate biofilm-related infections. This study was an attempt to repurpose chronic disease medications of the antihypertensive and antilipidemic drug classes, including candesartan cilexetil (CC) and ursodeoxycholic acid (UDCA), respectively, to be used as antibiofilm agents against the two infectious pathogens Staphylococcus aureus and Enterococcus faecalis. Crystal violet (CV) staining assay was used to evaluate the antibiofilm activity of the drugs. Real-time polymerase chain reaction (RT-PCR) was performed to determine the transcription levels of the biofilm-related genes (icaA and icaR in S. aureus and fsrC and gelE in E. faecalis) following treatment with different concentrations of CC and UDCA. we found that a concentration of greater than 1.5 µg/ml of CC significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates, and a concentration of greater than 50 µg/ml of UDCA significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates. Interestingly, the mRNA expression levels of biofilm-related genes were decreased in the two bacterial isolates at concentrations that were lower than the human pharmaceutical daily doses.

Ursodeoxycholic acid and COVID-19 infection in people with liver transplantation.

Ursodeoxycholic acid and COVID-19 infection in people with liver transplantation.

The effect of intrahepatic cholestasis of pregnancy and ursodeoxycholic acid treatment on Doppler parameters of fetal and maternal circulation.

We aimed to evaluate feto-maternal blood flow parameters using Doppler ultrasonography (USG) in pregnant women with intrahepatic cholestasis of pregnancy (ICP) and the effect of ursodeoxycholic acid (UDCA) treatment on these parameters. This prospective cohort study was performed at Dr. Sami Ulus Women's and Children's Health Teaching and Research Hospital, in Turkey between September 2022 and February 2023. Sixty pregnant women, 30 with ICP disease and 30 healthy women were included in the study. Obstetric Doppler parameters were measured by USG at diagnosis and after 48 hours of UDCA treatment for the ICP group. The obstetric Doppler parameters did not significantly differ in the ICP group and the healthy control group. The Doppler findings were similar after UDCA treatment in the ICP group. Gestational week at delivery and birth weight were lower in the ICP group in our study. We demonstrated that pregnant women with ICP had similar obstetric Doppler parameters when compared with healthy pregnant women and that the UDCA agent used for treatment of ICP disease did not affect these parameters.