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AIM: To investigate the activation of Cl- channels by sodium taurocholate （NaTC） in mouse pancreatic acinar cells. METHODS: The single isolated pancreatic acinar cells from FVB/N mice were prepared using collagenase digestion method. Whole-cell patch clamp technique was performed to record the currents. Intracellular adenosine triphosphate （ATP） dependence of the channels was examined via eliminating ATP from the pipette solution. Anion permeability of the channels was investigated with ion-exchange method. The pharmacological characteristics of the channels was confirmed by two Cl- channel blockers. The volume sensitivity of the channels was detected using 47% hypertonic bathing solution. Extracellular Ca2+ dependence of activating the channels was examined through eliminating Ca2+ from the bathing solution. Intracellular reactive oxygen species （ROS） level was detected by an oxidation-sensitive fluorescent probe, 2', 7'-dichlorofluorescin diacetate. The experiment was repeated 6 times in each group. RESULTS: Extracellular application of 5 mmol/L sodium taurocholate induced a Cl- current, exhibiting the properties of outward-rectification, a selectivity sequence of I- > Br- ≥ Cl- > gluconate- and intracellularATP dependence（ P<0. 01）. The currents were inhibited by chloride channel blocker 4, 4'-diisothiocyanatostilbene-2, 2'-disulfonic acid disodium salt hydrate （DIDS） and tamoxifen and by 47% hypertonicity stimulation （P<0. 01）. When ROS production was scavenged by N-acetyl-L-cysteine, the sodium taurocholate-induced Cl- currents were unaffected. The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS. Sodium taurocholate failed to induce Cl- currents when Ca2+ was absent in extracellular bathing solution （P>0. 05）. CONCLUSION: Sodium taurocholate activates Cl- channels in mouse pancreatic acinar cells, which is dependent on extracellular Ca2+ but not ROS pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Establishing a stable and reliable animal model of acute pancreatitis is of great significance for understanding its pathogenesis, pathophysiological characteristics, and clinical medication. Domestic and foreign studies have shown that cerulein, L-arginine, and sodium taurocholate can induce acute pancreatitis, but their pathophysiological characteristics and model characteristics are still unclear. OBJECTIVE: To establish an acute pancreatitis rat model using cerulein, L-arginine, and sodium taurocholate and to observe the changing patterns of model features at different time points. METHODS: Ninety-six healthy male Sprague-Dawley rats were randomly divided into normal group, cerulein group, L-arginine group, and sodium taurocholate group, with 24 rats in each group. Within each group, there were three subgroups (n=8 per group): 12-, 24-, and 48-hour subgroups. Cerulein was administered via intraperitoneal injection six times with a 1-hour interval. L-arginine was administered through two intraperitoneal injections with a 1-hour interval. Sodium taurocholate was injected for inducing acute pancreatitis models through retrograde injection into the bile-pancreatic duct. By examining the rat survival rate, gross morphology of the pancreas, calculating the pancreatic organ index, and measuring levels of amylase, lipase, alanine transaminase, aspartate transaminase, blood urea nitrogen, and creatinine, as well as observing pancreatic tissue pathological features through hematoxylin-eosin staining and conducting a pancreatic injury scoring, we evaluated the changing patterns of model features at different time points. RESULTS AND CONCLUSION: Compared with the normal group, the overall survival rate of rats was 100% in the cerulein group, 88% in the L-arginine group, and 96% in the sodium taurocholate group. The pancreatic organ index was increased in all groups. Gross observation indicated that, In the cerulein group, pancreatic edema, blurred lobes, and looseness were visible. In the L-arginine group, the pancreatic glands were enlarged and thickened with patchy bleeding. In the sodium taurocholate group, pancreatic tissue showed varying degrees of congestion and edema accompanied by scattered flakes of hemorrhage and necrosis. The levels of serum alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, amylase, and lipase in rats exhibited consistent changes. In the cerulein group, these parameters possibly peaked at 12 hours (P < 0.05) and then showed a declining trend. In the L-arginine group, they reached the highest levels at 24 hours (P < 0.05) and significantly decreased at 48 hours. In the sodium taurocholate group, serum amylase and lipase remained at higher levels at 12 hours with a slow decline trend (P < 0.05). Compared with the normal group, microscopic examination revealed mild acinar edema and widened interlobular spaces in the cerulein group, with a higher presence of inflammatory cells. In the L-arginine group, there was widening of interlobular spaces, extensive infiltration of inflammatory cells, and patchy necrotic areas. In the sodium taurocholate group, significant pancreatic edema, structural disarray, extensive necrotic foci, and inflammatory cell infiltration were observed. Compared with the normal group, the pathological scores of induced acute pancreatitis in all three models were significantly different at each time point (P < 0.05). Moreover, the pathological scores in each group increased over time, indicating a gradual worsening of pancreatic tissue damage. When comparing different models at the same time, there were differences in pathological scores, with the sodium taurocholate group having the highest scores, followed by the L-arginine group, and the cerulein group having the lowest scores. Analyzing the three models at the same time point, the most severe condition was in the sodium taurocholate group, which was characterized by pancreatic hemorrhage and necrosis, followed by the L-arginine group, which was characterized by necrosis, and the least severe condition was in the cerulein group, mainly characterized by edema. The serum biochemical index levels of the cerulein and L-arginine groups decreased at 48 hours, indicating that these two models may have a tendency to self-heal and belong to a self-limiting disease course. The serum biochemical index levels of the sodium taurocholate group decreased slowly after 12 hours. Therefore, pancreatic injury in the sodium taurocholate group might not be relieved after 48 hours or longer. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are a class of cholesterol-derived amphipathic molecules approved as new animal feed additives. However, the functional researches mainly focused on BAs mixture, and the influence of the individual BA on fishes was still limited. In the present study, Nile tilapia were fed basal diet with three levels of sodium taurocholate at 0 mg/kg (CON), 300 mg/kg (TCAL), and 600 mg/kg (TCAH) for 8 weeks. The results indicated that addition of sodium taurocholate did not significantly influence the growth performance. Instead, TCAH group had higher cholesterol accumulation with liver fibrosis. In TCAH group, the level of nuclear factor E2-related factor 2 (nrf2) signaling-associated oxidative stress factors significantly increased in the liver. Additionally, fish in TCAH group had the highest expression level of genes encoding endoplasmic reticulum (ER) stress and inflammatory cytokines in the liver. In conclusion, 300 mg/kg of sodium taurocholate did not significantly influence the growth performance of fish, while 600 mg/kg of sodium taurocholate markedly induced cholesterol accumulation and liver injury, suggesting that the application of taurocholic acid in aquafeed should be re-evaluated. [ABSTRACT FROM AUTHOR]

Sodium taurocholate (NaT) is a hydrophobic bile salt that exhibits varying toxicity and antimicrobial activity. The accumulation of BSs during their entero-hepatic cycle causes cytotoxicity in the liver and intestine and could also alter the intestinal microbiome leading to various diseases. In this research, the acute toxicity of sodium taurocholate in different concentrations (3000 mg/L, 1500 mg/L, 750 mg/L, 375 mg/L, and 0 mg/L) was investigated on four months old zebrafish by immersion in water for 96 h. The results were determined based on the fish mortality, behavioral response, and NMR metabolomics analysis which revealed LC50 of 1760.32 mg/L and 1050.42 mg/L after 72 and 96 h treatment, respectively. However, the non-lethal NaT concentrations of 750 mg/L and 375 mg/L at 96 h exposure significantly (p ≤ 0.05) decreased the total distance traveled and the activity duration, also caused surface respiration on the zebrafish. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) revealed that the metabolome of the fish treated with 750 mg/L was discriminated from that of the control by PC1. Major significantly downregulated metabolites by NaT-induction include valine, isoleucine, 2-hydroxyvalerate, glycine, glycerol, choline, glucose, pyruvate, anserine, threonine, carnitine and homoserine. On the contrary, taurine, creatine, lactate, acetate and 3-hydroxybutyrate were upregulated suggesting cellular consumption of lipids, glucose and amino acids for adenosine triphosphate (ATP) generation during immune and inflammatory response. whereby these metabolites were released in the process. In conclusion, the research revealed the toxic effect of NaT and its potential to trigger changes in zebrafish metabolism. [ABSTRACT FROM AUTHOR]

Background: Bilosomes are lipid vesicles that exhibit flexibility and deformability. They consist of phospholipids and amphiphilic bile salts. Compared to the normal vesicular systems such as liposomes and niosomes, bilosomes provide several notable advantages, including simplified manufacturing, cost-effectiveness, and enhanced stability. Aim: The main objective of the present work was to evaluate the effect of different bile salts on the physical properties that include entrapment efficiency, vesicle size, and polydispersity index(PDI). In addition, in vitro drug release for nisoldipine (NSD) loaded bilosomes was evaluated. Methods: Nisoldipine-loaded bilosomes were made using a thin film hydration technique. Cholesterol along with surfactant (span 60) was employed, and the formulation also contained several different bile salts, including sodium deoxycholate (SDC), sodium glycocholate (SGC), and sodium taurocholate (STC). Results: The developed NSD bilosomes exhibited an entrapment efficiency ranging from 44.2 ± 0.3 to 82.36 ± 0.80% and a vesicle size diameter in the nanometric dimensions (166 ± 1.83 to 237.8 ± 3.3 nm). An in-vitro release study revealed that formulas prepared with SDC bile salts showed higher drug release than SGC and STC formulas. Increasing the bile salt amount from 5 mg to 10 mg increases entrapment efficiency with increasing vesicle size. Further increase in bile salt led to decreased entrapment efficiency with increased vesicle size. SDC gives the best result in terms of entrapment efficiency and acceptable size. STC provides the largest particle size due to its high molecular weight compared to SGC and SDC. Conclusion: The SDC bile salt component is better suited for manufacturing NSD bilosomes. This is because this component yields the best results regarding high entrapment efficiency, nano size, and prolonged drug release. [ABSTRACT FROM AUTHOR]

Zehui Qin,1 Minhua Li,1,2 Juanjuan Cheng,1,2 Ziwei Huang,1,2 Gaoxiang Ai,1,2 Chang Qu,3 Youliang Xie,1 Yucui Li,1 Huijun Liao,4 Jianhui Xie,5– 7 Ziren Su1,2 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China; 3College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510006, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of ChinaCorrespondence: Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China, Dongguan Institute of Guangzhou University of Chinese Medicine, Dongguan, 523808, People’s Republic of China, Email suziren@gzucm.edu.cn Huijun Liao, Department of Clinical Pharmacy and Pharmaceutical Services, Huazhong University of Science and Technology Union Shenzhen Hospital (the 6th affiliated hospital of Shenzhen University), Shenzhen, People’s Republic of China, Email liaohuijun1016@163.comPropose: Berberine (BBR) is extensively studied as an outstanding anti-hyperuricemia drug. However, the clinical application of BBR was limited due to its poor absorption and low bioavailability. Therefore, there is an urgent necessity to find a novel drug formulation to address the issues of BBR in clinical application.Methods: Herein, we conducted the solubility, characterization experiments to verify whether BBR and sodium taurocholate (STC) self-assembled nanoparticles (STC@BBR-SANPs) could form. Furthermore, we proceeded the release experiment in vitro and in vivo to investigate the drug release effect. Finally, we explored the therapeutic effect of STC@BBR-SANPs on hyperuricemia (HUA) through morphological observation of organs and measurement of related indicators.Results: The solubility, particle size, scanning electron microscopy (SEM), and stability studies showed that the stable STC@BBR-SANPs could be formed in the BBR-STC system at ratio of 1:4. Meanwhile, the tissue distribution experiments revealed that the STC@BBR-SANPs could accelerate the absorption and distribution of BBR. In addition, the pharmacology study demonstrated that both BBR and STC@BBR-SANPs exhibited favorable anti-HUA effects and nephroprotective effects, while STC@BBR-SANPs showed better therapeutic action than that of BBR.Conclusion: This work indicated that STC@BBR-SANPs can be self-assembly formed, and exerts excellent uric acid-lowering effect. STC@BBR-SANPs can help to solve the problems of poor solubility and low absorption rate of BBR in clinical use, and provide a new perspective for the future development of BBR.Graphical Abstract: Keywords: berberine, sodium taurocholate, intermolecular interactions, self-assembled, nanoparticles, hyperuricemia

Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules. [ABSTRACT FROM AUTHOR]

Since discovery, the halophilic archaeal and bacterial strains were studied for their unique compounds such as pigments, proton pumps, compatible solutes and enzymes. Due to their tolerance to extreme salinities several research on using these organisms in various fields is conducted worldwide. Though sequencing is an efficient way of identifying an organism, the difficulty of selecting an optimal archaea primer for identification of archaea is tedious. Therefore, it is essential to discriminate them as bacteria or archaea before going for sequencing studies. There are several conventional and analytical techniques followed in discriminating and identifying the halophilic archaea and bacteria. The present study is an investigation of various conventional and analytical techniques such as morphological observations, biochemical tests, salinity optima, chloramphenicol susceptibility, growth in sodium taurocholate, lipid profiling by FAME analysis, FTIR and sequencing technique used in identifying halophilic community. This study also explains the disadvantages of each analysis and confirms the tests that can be used in the preliminary confirmation of halophilic archaea or bacteria. In the present study, halophilic archaeal and bacterial community from Solar salterns of Kelambakkam, Chennai, Tamilnadu and Tuticorin, Tamilnadu and Salt evaporation tank of tannery, Vellore, Tamilnadu were isolated and studied by various above-mentioned techniques. From the study, it was identified that FAME analysis out of other analyses can be used as preliminary method to identify and also distinguish the halophilic archaea and bacterial community. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aggregation behavior of choline taurocholate studied by Surface tension, ITC, and Fluorescence. • ITC and Fluorescence measurements indicated a sequential aggregation process. • CC, CDC, and CTC biosurfactants were investigated as contact dissolution agents for cholesterol. • Biosurfactants seem to have potential applications in cholesterol gallstone dissolution therapy. Bile salts belong to the category of biosurfactants naturally present in our system and are capable of excreting excess cholesterol and potentially toxic compounds. A major component of bile salts consists of cholic acids in humans, while sodium salt of taurocholic acid is the chief ingredient of the bile of carnivorous animals. The current work reports the synthesis of choline taurocholate (CTC) obtained by the replacement of sodium ions with a biocompatible and bulky counterion, choline through a salt metathesis reaction. The exchange of sodium ions with more hydrophobic biocompatible choline cation decreased the CMC values. The aggregation behavior of the newly synthesized biosurfactant was studied using surface tension (ST), isothermal titration calorimetry (ITC), and fluorescence measurements. All three methods show similar trends and convergence of the primary aggregates CMC values for both sodium taurocholate (NaTC) (7.3 mM by ST, 9.3 mM by ITC, and 9.6 mM by fluorescence) and CTC (5.8 mM by ST, 8.8 mM by ITC and 8.1 mM by fluorescence). However, ITC and fluorescence provided evidence of secondary aggregation at 37 mM by ITC, 42 mM by fluorescence, and 33 mM by ITC, 19 mM by fluorescence for NaTC and CTC respectively. Further in a simulated study, CTC and a previously reported choline salt of cholic acid (CC) and deoxycholic acid (CDC) were tested for their ability to solubilize cholesterol. The results were compared with those of ursodeoxycholic acid (UDCA), which is used as an approved therapy for the dissolution of gallstones. The order of cholesterol solubilization in the micelles was found to be in the following order CDC>CC>UDCA>CTC especially above 400 mg/2mL surfactant concentration in water. These studies explore the potential of CC, CDC, and CTC as potential contact dissolution agents for cholesterol gallstones without the use of any cosolvents. [ABSTRACT FROM AUTHOR]

[Display omitted] Previously, we reported that the combined use of spermine (SPM) and sodium taurocholate (STC) (SPM–STC) significantly improves the oral absorption of rebamipide (BCS class IV) and pulmonary absorption of interferon-α without any harmful histopathological changes in the gastrointestinal tract and lungs, respectively. In the present study, we examined the effect of SPM–STC on the transport of fluorescein isothiocyanate-labeled dextrans (FDs) across Caco-2 cell monolayers and attempted to clarify the mechanisms underlying the transport enhancement caused by SPM–STC. SPM–STC were found to significantly enhance the transport of FDs, while the treatment with SPM–STC was not harmful, and the decrease in transepithelial electrical resistance was transient and reversible. The voltage-clamp study clearly indicated that the opening of the paracellular route could be mainly responsible for the enhanced transport of FD-4. As for the mechanisms, it was found that SPM–STC caused a significant increase in membrane fluidity, which would lead to the enhanced transport of small-molecule drugs such as rebamipide. Since SPM–STC increased intracellular Ca2+ via Ca2+ uptake through Ca2+ channels and Ca2+ release from the endoplasmic reticulum stimulated by the IP 3 pathway, the subsequent possible activation of the MLCK signaling pathway would have led to the contraction of the actin–myosin ring. The rearrangement of tight junction-constituting proteins induced through the MAPK pathway has also been suggested as a possible mechanism for opening tight junctions. Claudin-4, a key protein constituting the tight junction, merged with F-actin along with the plasma membrane, was significantly decreased, which would be at least partial structural evidence for the tight-junction opening. [ABSTRACT FROM AUTHOR]

Brick dust molecules are usually poorly soluble in water and lipoidal components, making it difficult to formulate them in dosage forms that provide efficient pharmacological effects. A co-amorphous system is an effective strategy to resolve these issues. However, their glass transition temperatures (Tg) are relatively lower than those of polymeric amorphous solid dispersions, suggesting the instability of the co-amorphous system. This study aimed to formulate a stable co-amorphous system for brick dust molecules by utilizing sodium taurocholate (NaTC) with a higher Tg. A novel neuropeptide Y5 receptor antagonist (AntiY5R) and NaTC with Tg of 155 °C were used as the brick dust model and coformer, respectively. Ball milling formed a co-amorphous system for AntiY5R and NaTC (AntiY5R-NaTC) at various molar ratios. Deviation from the theoretical Tg value and peak shifts in Fourier-transform infrared spectroscopy indicated intermolecular interactions between AntiY5R and NaTC. AntiY5R-NaTC at equal molar ratios resulting in an 8.5-fold increase in AntiY5R solubility over its crystalline form. The co-amorphous system remained amorphous for 1 month at 25 °C and 40 °C. These results suggest that the co-amorphous system formed by utilizing NaTC as a coformer could stably maintain the amorphous state and enhance the solubility of brick dust molecules.

The improvement effect of the combined use of spermine (SPM), a polyamine, with sodium taurocholate (STC) on the pulmonary drug absorption was investigated utilizing poorly absorbable drugs with various molecular sizes in rats. The pulmonary absorption of rebamipide, a low molecular but poorly absorbable drug after oral administration, was significantly improved by the combined use of SPM with STC (SPM-STC formulation), while poly- L-lysine did not show a significant change in rebamipide absorption from the lungs. Furthermore, the safety of the SPM-STC formulation for the lungs was assessed in rats by the histopathological study and any local toxicity was not observed while poly-L-lysine, a typical chemical causing the toxicity for the epithelial cells, provided several histopathological changes. In addition, the SPM-STC formulation significantly improved the pulmonary absorption of fluorescein isothiocyanate dextran 4 (FD-4, Mw ca 4000) and interferon-α (IFN-α, Mw ca 25,000) as well. Our present results clearly indicated that the SPM-STC formulation significantly improved the pulmonary absorption of poorly absorbable small and large molecular drugs without any harmful effects on the lungs. Therefore, the SPM-STC formulation would be a useful one for the pulmonary absorption of drugs, specifically macromolecular ones, which are very difficult to be absorbed after oral administration. [ABSTRACT FROM AUTHOR]

A primary risk factor of cardiovascular disease is referred to the high concentration of plasma cholesterol. The alleviation of plasma cholesterol and inhibition of the catalytic domain of human 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), provides an alternative therapeutic candidate for reducing cholesterol. The present study evaluates the impact of rice bran protein hydrolysate (RBPH) on cholesterol homeostasis. The RBPH was produced by in vitro digestion of the extracted protein using commercial pepsin and pancreatic enzymes under optimized conditions. The hydrolysate was subjected to RP-HPLC and LC–MS profiling indicating three major peaks having masses ranging from 120 to 903 m/z. The degree of hydrolysis for producing the bioactive peptides has been marked with 61.53 ± 0.36%. SDS-PAGE reveals resistance to digestion compared to the native protein extracted from rice bran. The RBPH regulates the cholesterol level in two ways, the first potential role is by restricting the recycling of bile salts to the liver via direct excretion, second by exhibiting maximum micellar cholesterol inhibitory capacity and HMGCR inhibition in a dose dependent manner. The modulatory effect of RBPH on cholesterol homeostasis suggests hypocholesterolaemic property which could find an excellent application in developing physiological functional foods. [ABSTRACT FROM AUTHOR]

Background and Objectives: Peptic ulcer disease is a chronic disease affecting up to 10% of the world’s population. Proton pump inhibitors, such as lansoprazole are the gold standard in the treatment of ulcer disease. However, various studies have shown the effectiveness of garlic oil extracts in the treatment of ulcer disease. A cellular model can be established in the human gastric cell line by sodium taurocholate. The aim of this study was to explore the effects of garlic oil extracts pretreatment and LPZ addition in the cell culture model of peptic ulcer disease by examining oxidative stress and F-actin distribution. Materials and Methods: Evaluation was performed by determination of glutathione and prostaglandin E2 concentrations by ELISA; human gastric cell line proliferation by cell counting; expression of ATP-binding cassette, sub-family G, member 2; nuclear factor kappa B subunit 2 by RT PCR; and F-actin cytoskeleton visualization by semi-quantification of Rhodamine Phalloidin stain. Results: Our results showed significant reduction of cell damage after sodium taurocholate incubation when the gastric cells were pretreated with lansoprazole (p < 0.001) and increasing concentrations of garlic oil extracts (p < 0.001). Pretreatment with lansoprazole and different concentrations of garlic oil extracts increased prostaglandin E2 and glutathione concentrations in the cell culture model of peptic ulcer disease (p < 0.001). Positive correlation of nuclear factor kappa B subunit 2 (p < 0.01) with lansoprazole and garlic oil extracts pretreatment was seen, while ATP-binding cassette, sub-family G, member 2 expression was not changed. Treatment with sodium taurocholate as oxidative stress on F actin structure was less pronounced, although the highest concentration of garlic oil extracts led to a statistically significant increase of total amount of F-actin (p < 0.001). Conclusions: Hence, pretreatment with garlic oil extracts had gastroprotective effect in the cell model of peptic ulcer disease. However, further experiments are needed to fully elucidate the mechanism of this protective role.

• Genetic diversity within NTCP , HNF1α , TDP2 has an impact on treatment responseand liver condition. • TDP2 and HNF1α polymorphism is associated with HBsAg seroclearance and liver fibrosis. • NTCP and HNF1α polymorphisms influence on HBeAg/anti-HBe presence. • Our study provided evidence for the importance of recently described genes in HBV pathogenesis. • Identified SNPs may serve as biomarkers of disease progression, individual's risk of developing liver injury and/or treatment response. Hepatitis B virus (HBV) utilizes proteins encoded by the host to infect hepatocytes and replicate. Recently, several novel host factors have been identified and described as important to the HBV lifecycle. The influence of host genetic background on chronic hepatitis B (CHB) pathogenesis is still poorly understood. Here, we aimed to investigate the association of NTCP, FXR α , HNF1 α , HNF4 α, and TDP2 genetic polymorphisms with the natural course of CHB and antiviral treatment response. We genotyped 18 single-nucleotide polymorphisms using MALDI-TOF mass spectrometry in 136 patients with CHB and 100 healthy individuals. We investigated associations of the selected polymorphisms with biochemical, serological and hepatic markers of disease progression and treatment response. No significant differences in genotypic or allelic distribution between CHB and control groups were observed. Within TDP2 , rs3087943 variations were associated with treatment response, and rs1047782 modified the risk of advanced liver inflammation. Rs7154439 within NTCP was associated with HBeAg seroconversion after 48 weeks of nucleos(t)ide analogue treatment. HNF1α genotypes were associated with treatment response, liver damage and baseline HBeAg presence. HNF4α rs1800961 predicted PEG-IFNα treatment-induced HBsAg clearance in long-term follow up. This study indicates host genetic background relevance in the course of CHB and confirms the role of recently described genes for HBV infection. The obtained results might serve as a starting point for validation studies on the clinical application of selected genetic variants to predict individual risks of CHB-induced liver failure and treatment response. [ABSTRACT FROM AUTHOR]

Interaction of anionic bile salt sodium taurocholate (NaTaC) and anionic anti-inflammatory drug sodium salt of ibuprofen (NaIBU) in aqueous solutions together with in occurrence of 100 mmmol kg −1 NaCl and 250 mmmol kg −1 urea (NH2CONH2) using tensiometric and fluorometric techniques at 298.15 K temperature has been studied. A tensiometry study disclosed decreasing in surface tension ( γ ) along with critical micelle concentration ( cmc ) of NaIBU and NaTaC mixture, signifying a noteworthy interaction between studied components. Salt decreases the cmc of amphiphiles whereas urea increases their cmc in comparison to the aqueous solution. The solution mixture of NaIBU and NaTaC shows lower cmc value as compared to ideal cmc ( cmc id ) value indicating the non-ideality in the current studied systems. Other parameters regarding tensiometric technique such as micellar mole fraction of mixed micelles/mixed interface ( X 1 m / X 1 σ ), micellar/surface interaction parameter ( β m / β σ ), activity coefficients ( f 1 m / f 1 σ and f 2 m / f 2 σ ) of the mixed micelles/mixed interface, surface excess concentration ( Γ max ), excess Gibbs energy of mixed monolayer/mixed micelle formation ( Δ G ex σ / Δ G ex m ) etc. were estimated. The non-ideality of mixing expressed in terms of the interaction parameter ( β m / β σ ). Various thermodynamic parameters for current systems in all different media were obtained and discussed in detail. The aggregation number ( N agg ), as well as other related parameters regarding fluorescence study, were also evaluated. The higher values of N agg show the being of hydrophobic interactions along with sustains synergism. [ABSTRACT FROM AUTHOR]

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determinedin vitroin simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed theCmaxand AUC0–24were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT. Schematic illustration of QT-loaded mixed micelles. ST, P123 and QT were dissolved in EtOH, then evaporated to obtain thin film, followed by hydration to form a uniform system. [ABSTRACT FROM PUBLISHER]

A total of 210 European seabass fry with an average body weight of 0.51 ± 0.03 g were divided into seven experimental treatments (three replicates per treatment). The seven experimental diets (45.64% CP) were formulated to contain synthetic astaxanthin ( SA; 0.1 g kg−1), marigold flower meal ( MFM; 0.2 g kg−1) or crab waste meal ( CM; 10 g kg−1), with or without sodium taurocholate ( ST; 0.4 g kg−1); the control diet contained no supplementation. The experiment was conducted for 8 weeks. The results show that seabass fry fed the diets containing different sources of carotenoids, especially with ST, demonstrated higher growth efficiency, survival (%), feed efficiency, protein and ether extract contents of fish body. The best results were found with Diet MFM+ ST. Whole-body carotenoid levels increased significantly with all supplementation treatments; the highest level was observed with SA, followed by fish fed Diet MFM and Diet CM, especially with ST co-supplementation. Moreover, thiobarbituric acid-reactive substances were significantly reduced in fish fed the diets containing different sources of carotenoids compared to the control diet. The total antioxidant status significantly increased in fish fed Diet SA and Diet CM alone or with ST compared to the control group. In conclusion, these results reveal that Diet MFM+ ST is the most suitable treatment for improving growth, feed efficiency, and the protein and ether extract contents of seabass fry compared to other sources of carotenoids. The best oxidant/antioxidant balance and carotenoid content were achieved using SA, CM and MFM with ST supplementation. [ABSTRACT FROM AUTHOR]

For many years, there has been a search for a set of biochemical parameters that could facilitate the assessment of severity, prognosis, and administration of early and appropriate treatment in acute pancreatitis. Administration of treatment within the first 48 hours since admission is associated with many problems of distinguishing patients with a mild form of acute pancreatitis (AP) from those with a severe form of acute pancreatitis. Study aim: To assess the relationship between the extent of change in the concentration of 10 selected biochemical indicators: amylase, lipase, total bilirubin, creatinine, uric acid, aspartate transaminase, alanine transaminase, glucose, magnesium, and iron and histopathological lesions in the pancreas within 2 and 6 hours since induction of AP. The selected time periods correspond to the first and the second day of the disease in people, respectively. Material and methods: The experiments were conducted in 110 male Wistar rats weighing from 250 to 300 g. Experimental animals were divided into three groups: Z - a group in which the ranges of the studied factors and histological structure were established; K - a group of animals operated on which were injected with 0.9% NaCl into the biliary-pancreatic duct; E - a group of animals operated on in which acute pancreatitis was induced by an injection of 5% sodium taurocholate into the biliary-pancreatic duct. Animals from the K and E groups were randomly assigned to one of five subgroups from which the material for biochemical and histological examinations was collected at 2 h and 6 h since the induction of AP. Whole pancreases were dissected for histological examinations, and the samples were dyed with hematoxylin and saturated alcoholic eosin solution. The degree of pancreatic lesions was assessed according to the Spormann score. Quantitative variables were characterized by arithmetic means, standard deviations, medians, minimum and maximum values, and 95% CIs. Results: In histological preparations from rats from the E group, after 2 hours, edematous lesions, neutrophilic infiltrations in the pancreatic parenchyma, together with single petechiae started to appear and were observed. After 6 hours, the lesions became more intense, and minor foci of coagulation necrosis and minor foci of purulent inflammation in the fatty tissue appeared. Within 2 hours, statistically significant differences in the amount of four markers: creatinine, ALT, amylase, and magnesium were observed. After six hours, statistically significant differences in the amount of two markers: AST and glucose were seen. The correlations between histological assessments according to the Spormann scale and biochemical indicators were investigated, and it was observed that within 2 hours the intensity of pancreatitis increased together with an increase in AST. In group K, within 6 hours, the intensity of inflammatory infiltration increased together with an increase in creatinine concentration (correlation coefficient 0.95; p=0.0138). In group E, in the period of 2 hours, lesion intensity in the form of inflammatory infiltration increased together with an increase in the AST level (correlation coefficient 0.90; p=0.0063) and an increase in the iron level (correlation coefficient 0.78; p=0.0399). In the same group and in the same period, an increase in the AST level (correlation coefficient 0.79; p=0.0343) was associated with an increase in lesion intensity in the form of ecchymoses. Inflammatory infiltration increased (correlation coefficient -0.87; p=0.0117) within 6 hours, whereas the creatinine level decreased. Interesting results were obtained with the use of regression analysis - forward stepwise regression. In the period of 2 hours, if the creatinine level increased by 1, the intensity of lesions in acute pancreatitis decreased by 9.02, according to the Spormann score, while the other variables remained at a stable level. However, if ALT level increased by 1, the intensity of lesions in acute pancreatitis increased by 0.02, according to the Spormann score; and if the amylase level increased by 1, the intensity of lesions in acute pancreatitis increased by 0.01, according to the Spormann score, while the other variables remained at a stable level. Conclusions: Histopathological lesions occurred prior to changes in laboratory test results, whereas significant correlations with Spormann scores were seen in the case of changes in AST and creatinine levels. The study results confirm the fact that diagnostics in acute pancreatitis is very difficult and requires monitoring of many laboratory parameters. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phytosterol glycosyl derivatives inhibit the ability of bile salts to solubilize cholesterol. • Phytosterol glycosyl derivatives interact with sodium taurocholate via hydrogen bonds. • Phytosterol glycosyl derivatives have remarkable impacts on the changes of micelle structure. Hydrophilic phytosterol glycosyl derivatives are synthetic phytosterol analogues by coupling with the glycosyl moiety to improve the water solubility and bioaccessibility of free phytosterols. The aim of this study is to clarify the molecular interaction of phytosterol glycosyl derivatives with bile salts and the consequent impact on cholesterol solubilization. Sharp nonlinear decrease in the micellar solubility of cholesterol and accompanying changes in particle size, zeta potential and microtopography of mixed micelles were observed when phytosterol glycosyl derivatives were introduced in cholesterol-loaded bile salt micelles. These results suggested that β -sitosterol glycosyl derivatives molecules indeed participated in the formation of mixed micelles. Further, nuclear magnetic resonance showed that the structural change of mixed micelles was caused by the insertion of β -sitosterol glycosyl derivatives via hydrogen bonds with sodium taurocholate, which resulted in the low cholesterol solubilization. Moreover, the hydrogen-bond interactions were apparently influenced by the glycosyl moiety of β -sitosterol glycosyl derivatives. These molecular mechanisms may contribute to the development of cholesterol-absorption inhibitors. [ABSTRACT FROM AUTHOR]

Liposome (spherical vesicles) and cochleate (multilayer crystalline, spiral structure) formulations containing raloxifene have been developed having dimethyl-β-cyclodextrin (DM-β-CD) or sodium taurocholate (NaTC). Raloxifene was approved initially for the treatment of osteoporosis but it is also effective on breast tissue and endometrial cells. Raloxifene inhibits matrix metalloproteinase-2 (MMP-2) enzyme, which is known to be responsible for tumor invasion and the initiation of angiogenesis during the tumor growth. Therefore, raloxifene was selected as a model drug. A series of raloxifene-loaded liposome and cochleate formulations were prepared. In vitro release studies and in vivo tests were performed. Breast cancer cell lines (MCF-7) were also used to find the most effective formulation. Highest antitumor activity was observed, and MMP-2 enzyme was also found to be inhibited with raloxifene-loaded cochleates containing DM-β-CD. These developed formulations can be helpful for further treatment alternatives and new strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase in CXB solubility leads to a subsequent increase in permeability across intestinal barrier and (2) the presence of bile salts affects the solubility and permeability behavior of CXB formulations. By formulating CXB solid phospholipid (PL) dispersions with various PL-to-drug ratios using freeze drying, the present study illustrated that the enhancement of CXB solubility was not proportionally translated into enhanced permeability; both parameters were highly dependent on the PL-to-drug ratios as well as the dispersion media (i.e., the presence of 3-mM sodium taurocholate). This study highlights the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed. [ABSTRACT FROM AUTHOR]

The objective of the research was to detect the enhancement effect of sodium taurocholate on the absorption of cefquinome both in Caco-2 cells and rats. The absorption efficiency of cefquinome was determined by high performance liquid chromatography and calculated with apparent permeability coefficients (Papp) after Caco-2 cell monolayers treated odium taurocholate (2 mmol/L) and cefquinome. The results showed that the absorption of cefquinome in Caco-2 cell monolayers was significantly increased with the sodium taurocholate (2mmol/L). Similar results were also detected in the rats orally administrated with 1 mL PBS of cefquinome (20mg/mL) containing different concentration of sodium taurocholate (5 mmol/L, 10mmol/L and 20mmol/L) respectively. Compared with control group, sodium taurocholate at 10 and 20 mmol/L increased the absorption of cefquinome in rats from 0.26±0.04μg/mL to 0.57±0.03μg/mL, 0.78 ±0.07μg/mL respectively. These results indicated that sodium taurocholate could increase the intestinal permeability in a concentration-dependent mode, which will be useful for clinical treatment. [ABSTRACT FROM AUTHOR]