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ABSTRACT The marine bacterium Vibrio parahaemolyticus is a major cause of seafood-borne gastroenteritis in humans and of acute hepatopancreatic necrosis disease in shrimp. Bile acids, produced by the host and modified into secondary bile acids by commensal bacteria in the gastrointestinal tract, induce the virulence factors leading to disease in humans and shrimp. Here, we show that secondary bile acids also activate this pathogen’s type VI secretion system 1, a toxin delivery apparatus mediating interbacterial competition. This finding implies that Vibrio parahaemolyticus exploits secondary bile acids to activate its virulence factors and identify the presence of commensal bacteria that it needs to outcompete in order to colonize the host.IMPORTANCEBacterial pathogens often manipulate their host and cause disease by secreting toxic proteins. However, to successfully colonize a host, they must also remove commensal bacteria that reside in it and may compete with them over resources. Here, we find that the same host-derived molecules that activate the secreted virulence toxins in a gut bacterial pathogen, Vibrio parahaemolyticus, also activate an antibacterial toxin delivery system that targets such commensal bacteria. These findings suggest that a pathogen can use one cue to launch a coordinated, trans-kingdom attack that enables it to colonize a host.

The global pathogen Clostridioides difficile is a well-studied organism, and researchers work on unraveling its fundamental virulence mechanisms and biology. Prophages have been demonstrated to influence C. difficile toxin expression and contribute to the distribution of advantageous genes. All these underline the importance of prophages in C. difficile virulence. Although several C. difficile prophages were sequenced and characterized, investigations on the entire active virome of a strain are still missing. Phages were mainly isolated after mitomycin C-induction, which does not resemble a natural stressor for C. difficile. We examined active prophages from different C. difficile strains after cultivation in the absence of mitomycin C by sequencing and characterization of particleprotected DNA. Phage particles were collected after standard cultivation, or after cultivation in the presence of the secondary bile salt deoxycholate (DCA). DCA is a natural stressor for C. difficile and a potential prophage-inducing agent. We also investigated differences in prophage activity between clinical and non-clinical C. difficile strains. Our experiments demonstrated that spontaneous prophage release is common in C. difficile and that DCA presence induces prophages. Fourteen different, active phages were identified by this experimental procedure. We could not identify a definitive connection between clinical background and phage activity. However, one phage exhibited distinctively higher activity upon DCA induction in the clinical strain than in the corresponding non-clinical strain, although the phage is identical in both strains. We recorded that enveloped DNA mapped to genome regions with characteristics of mobile genetic elements other than prophages. This pointed to mechanisms of DNA mobility that are not well-studied in C. difficile so far. We also detected phage-mediated lateral transduction of bacterial DNA, which is the first described case in C. difficile. This study significantly contributes to our knowledge of prophage activity in C. difficile and reveals novel aspects of C. difficile (phage) biology. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy and safety of four kinds of intravenous preparations of amphotericin B in the treatment of fungal infections based on network Meta-analysis. METHODS: PubMed, Scopus, Web of Science, the Cochrane Library, Embase, CNKI, Wanfang Data, VIP and CBM were retrieved to collect the randomized controlled trial (RCT) of amphotericin B with triazole or echinocandins in the treatment of fungal infections for network Meta-analysis. The retrieval time was from the establishment of the database to Aug. 5th, 2023. The quality of literature was evaluated according to GRADE. RESULTS: A total of 16 literature with 4 365 patients were included. In terms of efficacy, amphotericin B liposomes > amphotericin B deoxycholate > amphotericin B colloid dispersion, the difference was statistically significant (P <0. 05), while amphotericin B liposomes complex had no statistical significance compared with other amphotericin B (P>0. 05). There was no significant difference in the total incidence of adverse drug reactions among four kinds of intravenous preparations of amphotericin B (P > 0. 05). Subgroup analysis showed that amphotericin B deoxycholate had higher neurotoxicity than amphotericin B colloidal dispersion, with statistically significant differences (P<0. 05). CONCLUSIONS: Among the four kinds of intravenous preparations of amphotericin B, efficacy of liposome dosage form is better than that of traditional dosage form of deoxycholate. The efficacy of colloid dispersion dosage form is significantly lower than that of traditional dosage form, with lower toxicity of nervous system. Due to the limited number of literature included in the study, there may be publication bias, more clinical literature with large sample size and high quality are needed to confirm the results and conclusions of this study. [ABSTRACT FROM AUTHOR]

The interaction of nutrients and bacterial-derived products and their enteroendocrine effects are still enigmatic. We used the human enteroendocrine tumour cell line P-STS isolated from the terminal ileum as cellular sentinel. In this model, P-STS cells react to acetylcholine or histamine with an increase in intracellular calcium mediated by T-type voltage-gated calcium channels followed by serotonin secretion. Incubation with the secondary bile acid deoxycholate inhibited the calcium response to acetylcholine but not to histamine. No response to other nutrients or bacterial products tested (i.e. palmitate, lactate, acetate, proprionate, butyrate, the OR51E1 ligand isovalerate and the HCA2 ligand β-hydroxybutyrate) could be observed. The bile acid receptor TGR5 agonist CCDC did not inhibit the acetylcholine-induced calcium response, and the free fatty acid receptor 2 agonist 4-CMTB had no enhancing effect on the calcium response to acetylcholine. Only butyrate had an enhancing effect on the calcium response in P-STS cells when added for short-time pre-incubation before challenge with acetylcholine. From our data we propose i) an inhibitory effect of deoxycholate at the muscarinic acetylcholine receptor M3 without involvement of TGR5, and that ii) high butyrate concentrations derived from bacterial metabolism of carbohydrates might increase intestinal release of serotonin and potentially also other gut hormones and satiety-inducing peptides independently of known butyrate receptors, thereby influencing intestinal motility and ion secretion.

The global pathogen Clostridioides difficile is a well-studied organism, and researchers work on unraveling its fundamental virulence mechanisms and biology. Prophages have been demonstrated to influence C. difficile toxin expression and contribute to the distribution of advantageous genes. All these underline the importance of prophages in C. difficile virulence. Although several C. difficile prophages were sequenced and characterized, investigations on the entire active virome of a strain are still missing. Phages were mainly isolated after mitomycin C-induction, which does not resemble a natural stressor for C. difficile. We examined active prophages from different C. difficile strains after cultivation in the absence of mitomycin C by sequencing and characterization of particle-protected DNA. Phage particles were collected after standard cultivation, or after cultivation in the presence of the secondary bile salt deoxycholate (DCA). DCA is a natural stressor for C. difficile and a potential prophage-inducing agent. We also investigated differences in prophage activity between clinical and non-clinical C. difficile strains. Our experiments demonstrated that spontaneous prophage release is common in C. difficile and that DCA presence induces prophages. Fourteen different, active phages were identified by this experimental procedure. We could not identify a definitive connection between clinical background and phage activity. However, one phage exhibited distinctively higher activity upon DCA induction in the clinical strain than in the corresponding non-clinical strain, although the phage is identical in both strains. We recorded that enveloped DNA mapped to genome regions with characteristics of mobile genetic elements other than prophages. This pointed to mechanisms of DNA mobility that are not well-studied in C. difficile so far. We also detected phage-mediated lateral transduction of bacterial DNA, which is the first described case in C. difficile. This study significantly contributes to our knowledge of prophage activity in C. difficile and reveals novel aspects of C. difficile (phage) biology.

ABSTRACTBacteroides fragilis comprises 1%–5% of the gut microbiota in healthy humans but can expand to >50% of the population in ulcerative colitis (UC) patients experiencing inflammation. The mechanisms underlying such microbial blooms are poorly understood, but the gut of UC patients has physicochemical features that differ from healthy patients and likely impact microbial physiology. For example, levels of the secondary bile acid deoxycholate (DC) are highly reduced in the ileoanal J-pouch of UC colectomy patients. We isolated a B. fragilis strain from a UC patient with pouch inflammation (i.e., pouchitis) and developed it as a genetic model system to identify genes and pathways that are regulated by DC and that impact B. fragilis fitness in DC and crude bile. Treatment of B. fragilis with a physiologically relevant concentration of DC reduced cell growth and remodeled transcription of one-quarter of the genome. DC strongly induced expression of chaperones and select transcriptional regulators and efflux systems, and down-regulated protein synthesis genes. Using a barcoded collection of ≈50,000 unique insertional mutants, we further defined B. fragilis genes that contribute to fitness in media containing DC or crude bile. Genes impacting cell envelope functions including cardiolipin synthesis, cell surface glycosylation, and systems implicated in sodium-dependent bioenergetics were major bile acid fitness factors. As expected, there was limited overlap between transcriptionally regulated genes and genes that impacted fitness in bile when disrupted. Our study provides a genome-scale view of a B. fragilis bile response and genetic determinants of its fitness in DC and crude bile.IMPORTANCEThe Gram-negative bacterium Bacteroides fragilis is a common member of the human gut microbiota that colonizes multiple host niches and can influence human physiology through a variety of mechanisms. Identification of genes that enable B. fragilis to grow across a range of host environments has been impeded in part by the relatively limited genetic tractability of this species. We have developed a high-throughput genetic resource for a B. fragilis strain isolated from a UC pouchitis patient. Bile acids limit microbial growth and are altered in abundance in UC pouches, where B. fragilis often blooms. Using this resource, we uncovered pathways and processes that impact B. fragilis fitness in bile and that may contribute to population expansions during bouts of gut inflammation.

ABSTRACTEnteric bacteria need to adapt to endure the antibacterial activities of bile salts in the gut. Phospholipase A (PldA) is a key enzyme in the maintenance of bacterial membrane homeostasis. Bacteria respond to stress by modulating their membrane composition. Campylobacter jejuni is the most common cause of human worldwide. However, the mechanism by which C. jejuni adapts and survives in the gut environment is not fully understood. In this study, we investigated the roles of PldA, bile salt sodium deoxycholate (DOC), and oxygen availability in C. jejuni biology, mimicking an in vivo situation. Growth curves were used to determine the adaptation of C. jejuni to bile salts. RNA-seq and functional assays were employed to investigate the PldA-dependent and DOC-induced changes in gene expression that influence bacterial physiology. Survival studies were performed to address oxidative stress defense in C. jejuni. Here, we discovered that PldA of C. jejuni is required for optimal growth in the presence of bile salt DOC. Under high oxygen conditions, DOC is toxic to C. jejuni, but under low oxygen conditions, as is present in the lumen of the gut, C. jejuni benefits from DOC. C. jejuni PldA seems to enable the use of iron needed for optimal growth in the presence of DOC but makes the bacterium more vulnerable to oxidative stress. In conclusion, DOC stimulates C. jejuni growth under low oxygen conditions and alters colony morphology in a PldA-dependent manner. C. jejuni benefits from DOC by upregulating iron metabolism in a PldA-dependent manner.

Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers.

The marine bacterium Vibrio parahaemolyticus is a major cause of seafood-borne gastroenteritis in humans and of acute hepatopancreatic necrosis disease in shrimp. Bile acids, produced by the host and modified into secondary bile acids by commensal bacteria in the gastrointestinal tract, induce the virulence factors leading to disease in humans and shrimp. Here, we show that secondary bile acids also activate this pathogen's type VI secretion system 1, a toxin delivery apparatus mediating interbacterial competition. This finding implies that Vibrio parahaemolyticus exploits secondary bile acids to activate its virulence factors and identify the presence of commensal bacteria that it needs to outcompete in order to colonize the host.IMPORTANCEBacterial pathogens often manipulate their host and cause disease by secreting toxic proteins. However, to successfully colonize a host, they must also remove commensal bacteria that reside in it and may compete with them over resources. Here, we find that the same host-derived molecules that activate the secreted virulence toxins in a gut bacterial pathogen, Vibrio parahaemolyticus , also activate an antibacterial toxin delivery system that targets such commensal bacteria. These findings suggest that a pathogen can use one cue to launch a coordinated, trans -kingdom attack that enables it to colonize a host., Competing Interests: The authors declare no conflict of interest.

Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low‐grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO−)‐mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC‐ECM), which was obtained by deoxycholate (DOC)‐based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO−‐mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO− was found in the serum of AS mice, and ONOO− could stimulate the development of AS. SMC‐ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO−‐mediated oxidization destroyed the three‐dimensional structure of SMC‐ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation‐ and oxidative stress‐related genes was significantly increased in ECM subjected to ONOO−‐mediated oxidization, thereby contributing to AS progression. ONOO−‐mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs. [ABSTRACT FROM AUTHOR]

Background: The skin of the neck is often pinched during minimally invasive esthetic procedures for the double chin using a lipolytic agent in order to facilitate injecting into the subcutaneous fat layer rather than under the platysma muscle. However, how the neck tissue layers move during the pinch manipulation is not well understood. Aims: To determine which layer of the neck is lifted during pinching and to evaluate the usefulness of the pinch manipulation during injection therapy. Methods: The pinched submentum of a living person was scanned using MRI, and ultrasonography was also performed in the same area in both resting and pressed states. At four sites on a fresh cadaver, the skin of the neck was pinched and the elevated neck skin was excised. The exposed areas were grossly examined. Results: MRI scanning revealed that the pinch manipulation extended the subcutaneous fat layer and moved the platysma muscle to a deeper location. Ultrasonography revealed that the thickness of each layer of the neck was reduced when pressing the neck. In the cadaver examination, pinching resulted in part of the subcutaneous fat lifting, and this was removed when the lifted skin was cut, leaving the platysma muscle intact. Conclusions: When performing an esthetic procedure that involves injecting a lipolytic agent into the submental area, the pinch manipulation is a very useful technique for ensuring a safe procedure that avoids injecting into the deep layer under the platysma muscle. [ABSTRACT FROM AUTHOR]

In the mammalian's cells, a higher level of plasma cholesterol is a risk factor for cardiovascular disease. Human 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a regulatory cholesterol synthesis enzyme in the mevalonate pathway. Statins are the major synthetic drugs as inhibitor of HMGCR but it's associated with adverse effect so it is advisable to provide alternative therapeutic candidate for cholesterol homeostasis. The current investigation indicates the cholesterol-lowering effect of Pigeon pea by-product protein hydrolysate (PBPH) fraction by inhibition of HMGCR and cholesterol micelles. The PBPH fractions control the cholesterol levels by two ways, first, PBPH fractions (> 30 kDa and > 10 < 30 kDa) significantly block the recycling of bile salts to the hepatocyte cells with direct excretion via the digestive system. Second, PBPH fraction (< 10 kDa) exhibits inhibition of cholesterol micellar, as well as the catalytic domain of HMGCR in a dose dependant manner. The inhibition of HMGCR has been verified through HMGCR protein expression in the cholesterol synthesis pathway. The HMGCR protein shows significant up-regulation upon treatment with PBPH fraction < 10 kDa in HepG2 cells. The PBPH fraction shows potent inhibitory capacity on cholesterol homeostasis suggesting it to have hypocholesterolemic properties. It could find an admirable application for the development of functional foods. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of deoxycholic acid (DOC) for SMF reduction. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched PubMed/MEDLINE, EMBASE, and Cochrane databases until June 2020. Efficacy outcomes: Clinician-Reported Submental Fat Rating Scale; Patient-Reported Submental Fat Rating Scale; Subject Self-Rating Scale; SMF reduction measured using caliper and resonance magnetic imaging; Early therapeutic success. Safety outcomes: Withdrawals due to adverse events (AEs), Rates of AEs, Skin laxity. Results: Five studies were included, comprising 1,838 participants. DOC (1 or 2 mg/cm2) had greater improvement in all efficacy measures compared to placebo. No differences were seen between both doses of DOC. Withdrawals due to AEs were low with 1 and 2 mg/cm2 of DOC (6.8% vs. 9.9%, respectively), and there was no difference between the two doses (p = 0.22). AEs were usually associated with the injection site, were predominantly transient, and commonly resolved within the treatment session interval. Injection site pain, hematoma, anesthesia/numbness, erythema, and swelling/edema were the most common AEs. There was no difference in their prevalence between both doses of DOC. Conclusions: DOC is effective and safe for SMF reduction with no differences between doses of 1 and 2 mg/cm2. [ABSTRACT FROM AUTHOR]

Background: Lipomas are benign adipocytic tumours. Surgical excision is the gold standard for treating such lipomas, but it results in unaesthetic scarring. Methods: A total of 126 patients were randomised into two groups. The patients in Group A underwent mesotherapy (n = 66) and those in Group B underwent surgery (n = 60). The patients in Group A group received six sessions of mesotherapy treatment at 2-week intervals. Both groups were followed up for 12 weeks, during which they were assessed for complications arising from treatment, reduction of the size of the lipoma and cosmetic outcomes. Results: The overall mean age of the patients was 32.93 (± 10.1) years old and the mean volume of the lipomas was 2.29 (± 3.8) mL. A 55.86% (P = 0.0032) mean reduction in the volume of lipomas was noted in the patients who received mesotherapy, while one patient showed a gain of 16% by volume. The patients in Group A (cosmetic score ≥ 4: 63%) were happier with the treatment than those in Group B (cosmetic score ≥ 4: 21%). Conclusion: Our findings indicate that mesotherapy modestly reduces the volume of lipomas with very few and minor complications and excellent cosmetic outcomes. [ABSTRACT FROM AUTHOR]

Purpose: We report a case of rhino-orbital-cerebral mucormycosis (ROCM) with focal anterior cerebritis treated favorably with retrobulbar amphotericin B and systemic antifungals. Observations: A 55-year-old diabetic male presented to the emergency department with left sided proptosis, left temple headache, maxillary sinus pain, and diplopia of 3 days duration. Biopsy results from the left middle turbinate, ethmoid, and maxillary sinus revealed broad and irregular non-septate hyphae consistent with mucormycosis. Despite treatment with intravenous antifungals and endoscopic debridement of the sinuses, his condition did not improve. Disease progression included the development of left ophthalmoplegia and left-sided cerebritis. The patient received retrobulbar injection of deoxycholate amphotericin B with eventual disease resolution, without exenteration. Conclusions: We present a case of ROCM with associated cerebritis that responded to retrobulbar amphotericin B, without exenteration.

The antiinflammatory activity of purified oat 1-3,1-4-β-d-glucan against acute gastritis (sodium deoxycholate induced) model in rats was investigated as second part of experiment studying impact of oat β-glucan on inflammatory states in gastrointestinal tract (first part was related to enteritis). 48 rats (Spraque-Dawley males, two groups – control and gastritis) were fed high and low molecular weights (MW) β-glucan. Antioxidant defense parameters – SOD, TAS, GSH, GSSG and inflammation markers – TBARS, TNF-α, IL-10 and IL-12 were analyzed. Strong activity of both fractions was observed; high MW β-glucan caused high TNF-α decrease in both experimental groups while low MW β-glucan decreased the concentration of IL-10 in gastritis group. Both fractions significantly support innate antioxidant defense of stomach tissue not only in gastritis but in healthy state as well. The results reveal the potential therapeutic activity of purified oat β-glucan in acidic environment of stomach at acute gastritis states.

Importance: The Gram-negative bacterium Bacteroides fragilis is a common member of the human gut microbiota that colonizes multiple host niches and can influence human physiology through a variety of mechanisms. Identification of genes that enable B. fragilis to grow across a range of host environments has been impeded in part by the relatively limited genetic tractability of this species. We have developed a high-throughput genetic resource for a B. fragilis strain isolated from a UC pouchitis patient. Bile acids limit microbial growth and are altered in abundance in UC pouches, where B. fragilis often blooms. Using this resource, we uncovered pathways and processes that impact B. fragilis fitness in bile and that may contribute to population expansions during bouts of gut inflammation., Competing Interests: The authors declare no conflict of interest.

Background: Synthetic deoxycholic acid (DCA) has been approved as an injectable drug for the nonsurgical reduction of submental fat. Objective: In this study, we evaluated the fat-reducing effects of a new formula containing a low dose of DCA and fat dissolution by topical application of DCA. Methods: Sodium deoxycholate (99.1% pure) and the new formulation containing 10% DCA were injected or topically applied to the dorsa of obese mice (induced by a high-fat diet). The rate of change in body weight was evaluated, together with comparisons of micro-computed tomography images, body composition measurements, and histology findings. Results: The results showed that the new formula containing low-dose DCA was as effective as the older high-dose formulation with respect to the rate of change in body weight and reductions in subcutaneous fat pad area, body fat weight, and the thickness of the subcutaneous fat layer. Furthermore, topical application of the high-dose, but not the low-dose, formulation yielded promising effects. Conclusions: The development of a better protocol for the high-dose preparation, including dose optimization and application methods that minimize the adverse effects of DCA, merits further study. No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors - www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Abstract Quantitative Polymerase Chain Reaction (qPCR) is a molecular method commonly used to detect and quantify bacterial DNA on food but is limited by its inability to distinguish between live and dead cell DNA. To overcome this obstacle, propidium monoazide (PMA) alone or with deoxycholate (DC) was used to prevent dead cell detection in qPCR. qPCR methods were used to detect strains of Escherichia coli O157, which can cause infection in humans with an infectious dose of less than 10 cells. A 5 strain E. coli O157:H7 cocktail was inoculated onto beef steaks and treated with interventions used in meat facilities (lactic acid (5%), peroxyacetic acid (200 ppm) or hot water (80 °C for 10 s)). Treatment of PMA or PMA + DC was applied to samples followed by DNA extraction and quantification in qPCR. RNA was also quantified in addition to conventional plating. For lactic acid intervention, qPCR DNA quantification of E. coli O157:H7 yielded 6.59 ± 0.21 and 6.30 ± 0.11 log gene copy #/cm2 for control and lactic acid samples, respectively and after treatment with PMA or PMA + DC this was further reduced to 6.31 ± 0.21 and 5.58 ± 0.38, respectively. This trend was also observed for peroxyacetic acid and hot water interventions. In comparison, RNA quantification yielded 7.65 ± 0.13 and 7.02 ± 0.38 log reverse transcript/cm2 for rRNA control and lactic acid samples, respectively, and for plating (LB), 7.51 ± 0.06 and 6.86 ± 0.32 log CFU/cm2, respectively. Our research determined that treatment of PMA + DC in conjunction with qPCR prevented dead cell DNA detection. However, it also killed cells injured from intervention that may have otherwise recovered. RNA quantification was more laborious and results had higher variability. Overall, quantification with conventional plating proved to be the most robust and reliable method for live EHEC detection on beef. Highlights • The accuracy of 5 methods to quantify live cells of E. coli O157 on beef was compared. • PMA treatment alone did not prevent all dead cell DNA detection in qPCR. • PMA with deoxycholate prevented all dead and likely injured cell DNA detection in qPCR. • RNA quantification was more laborious and had more variability in live cell detection. • Of the 5 methods, conventional plating was the most robust and reliable method. [ABSTRACT FROM AUTHOR]

Abstract Organic–inorganic layered double hydroxides (LDHs) were obtained by using a microwave-assisted method to intercalate cholate or deoxycholate ion into an Mg, Al mixed LDH. Based on the X-ray diffraction and Raman spectra for the resulting LDHs, a treatment time of only 1 h sufficed to ensure complete intercalation of the organic anions. This makes the proposed synthetic method more expeditious than existing alternatives for the same purpose. Based on the baseline spacing for the organo-LDHs, the organic anions were intercalated with no cross-over between their molecular chains. The interlayer distance of the solids was confirmed by high-resolution transmission electron micrographs (HR-TEM). As revealed by thermogravimetric monitoring measurements, and confirmed by Raman spectra, the decomposition temperature for the LDHs increased considerably upon intercalation of the organic anion. Graphical abstract Image 1045 Highlights • First synthesis of LDH containing cholate anions. • Synthetic method more expeditious than existing alternatives for the same purpose. • The resulting solids possess a high crystallinity. • More than 1 h of MW treatment have an adverse impact on crystallinity. [ABSTRACT FROM AUTHOR]

Plastein is a thixotropic product of protease-induced peptide aggregation. This study evaluated the effects of the modified peptide structure of plastein on its affinity for a secondary bile acid. Casein plastein formation resulted in decreased free amino nitrogen and increased mean particle size, surface hydrophobicity and hydrophobic-to-hydrophilic amino acid ratio of the peptides. The net negative surface charge of casein hydrolysate (CH) was decreased (P

Enteric bacteria need to adapt to endure the antibacterial activities of bile salts in the gut. Phospholipase A (PldA) is a key enzyme in the maintenance of bacterial membrane homeostasis. Bacteria respond to stress by modulating their membrane composition. Campylobacter jejuni is the most common cause of human worldwide. However, the mechanism by which C. jejuni adapts and survives in the gut environment is not fully understood. In this study, we investigated the roles of PldA, bile salt sodium deoxycholate (DOC), and oxygen availability in C. jejuni biology, mimicking an in vivo situation. Growth curves were used to determine the adaptation of C. jejuni to bile salts. RNA-seq and functional assays were employed to investigate the PldA-dependent and DOC-induced changes in gene expression that influence bacterial physiology. Survival studies were performed to address oxidative stress defense in C. jejuni . Here, we discovered that PldA of C. jejuni is required for optimal growth in the presence of bile salt DOC. Under high oxygen conditions, DOC is toxic to C. jejuni , but under low oxygen conditions, as is present in the lumen of the gut, C. jejuni benefits from DOC. C. jejuni PldA seems to enable the use of iron needed for optimal growth in the presence of DOC but makes the bacterium more vulnerable to oxidative stress. In conclusion, DOC stimulates C. jejuni growth under low oxygen conditions and alters colony morphology in a PldA-dependent manner. C. jejuni benefits from DOC by upregulating iron metabolism in a PldA-dependent manner.

Deoxycholate (deoxycholic acid) and collagenase are naturally occurring substances whose ability to degrade adipose tissue and collagen respectively has given rise to a variety of therapeutic applications. This article will discuss the indications for the use of deoxycholic acid, primarily its well-established role in the non-surgical reduction of submental fat, with a focus on patient assessment, procedural technique, risks, pitfalls, and key clinical tips. It will also review the indications for collagenase as a degradation therapy, its mechanism of action, and benefits in the management of wound healing, scarring, and adipose tissue modification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Lipolytic substance injections to reduce localized fat have been extensively used because it is a low-invasive method. This review aimed to evaluate the efficacy and safety of deoxycholic acid in submental fat reduction compared to a placebo and investigate the potential industry sponsorship bias in the results of randomized clinical trials on this topic. Ten electronic databases were extensively searched for randomized clinical trials without restriction on language and year of publication. Two reviewers extracted the data and assessed the individual risk of bias in the studies with the RoB 2.0 tool. The industry sponsorship bias was evaluated according to citations in the articles regarding industry funding/sponsorship throughout the texts. Fixed and random effects meta-analyses were performed, and the results were reported in Risk Ratio (RR) at a 95% Confidence Interval (95% CI). The initial search provided 5756 results, of which only five were included. Only two studies had a low risk of bias. All studies showed a potential industry bias. The meta-analysis showed that patients treated with deoxycholic acid had significant positive results for all efficacy outcomes and a higher risk of fibrosis, pain, erythema, numbness, swelling, edema, pruritus, nodules, headache, and paresthesia. The low to moderate certainty of evidence found allows concluding that deoxycholic acid is effective in submental fat reduction, causing well-tolerated adverse effects. However, all eligible studies showed a potential industry bias., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Phosphatidylcholine and deoxycholate (PC-DC) injections have been used as nonsurgical alternatives to liposuction. DC as a constituent for lipolysis has recently been approved by the US Food and Drug Administration. Aim: PC and DC have independently been used in lipolysis. We hereby present a systematic review of literature on injection lipolysis and share our experience of using DC in combination with PC for injection lipolysis. We have retrospectively evaluated the effects of PC-DC treatments in varied age groups, both sexes, and over different target areas. Materials and Methods: This study spans over 14 years wherein 1269 patients of different age groups and sex were treated with injection lipolysis with PC-DC combination. The PC-DC cocktail injection was given to all patients for an average four sessions every 4 weeks, and the results were assessed after 8 weeks from the last session. Results: The effects were best appreciated over the face (malar, jawline, and submental areas) and upper arm, whereas average effect was observed on the thighs and around the knees. We have also used lipolysis as a primary modality as well as a touch-up modality following liposuction. The results are better appreciated in primary lipolysis. The need for follow-up sessions (1-2 sessions) of lipolysis and the quantification of results in subsequent sessions reveal that maximal improvement is achieved in the first session. Conclusion: PC-DC cocktail used for lipolysis as a local administration is effective for reducing unwanted fat. It shows great efficacy in treating localized fat, especially over the face and bra roll in the women of younger age group (20-30 years). [ABSTRACT FROM AUTHOR]

In the present study pain/discomfort reduction in submental fullness treatment with the injections of a DC based drug (ATX-101, Allergan, Dublin, Ireland) premixed with lidocaine 2% on a sample of 12 patients retrospectively evaluated has been performed All patients indicated improvement in skin tightening from the 2nd month postinjection. Three patients had minor ecchymoses at the injection sites, which resolved spontaneously within 10 days posttreatment. One patient experienced dysesthesia of the treated area, which lasted approximately 40 days and resolved spontaneously. No other complications--such as nerve paresis or alopecia--were recorded. No patient required analgesic drugs postinjection. [ABSTRACT FROM AUTHOR]

Madelung’s disease is characterised by multiple symmetric abnormal fat masses in the head, neck and upper limbs. Surgical excision or liposuction is the only realistic available option, although palliative in nature. The serial intralipotherapy with phosphatidylcholine/deoxycholate has been proposed as a non-invasive treatment of Madelung’s disease. The authors used serial intralipotherapy with phosphatidylcholine/deoxycholate in two patients affected by Madelung’s disease. Three injections per lesion per patient were performed with 1 month’s interval. Pre- and 6 months’ post-treatment dimensions were assessed with ultrasound scan and patients were observed along a 5 years’ clinical follow-up. A 42.5% average size reduction was reported in all treated lesions. About 33% recurrence rate was observed in the 5 years’ follow-up. We confirm the efficacy of intralipotherapy in the non-invasive palliative treatment of Madelung’s disease, as a valid option to reduce the volume and limit the growth of the pathological adipose masses.

Background: candidiasis is the primary fungal infection encountered in patients undergoing prolonged hospitalization, and the fourth leading cause of nosocomial bloodstream infections. One of the most important Candida spp. virulence factors is the ability to form biofilms, which are extremely refractory to antimicrobial therapy and very difficult to treat with the traditional antifungal therapies. It is known that the prophylaxis or treatment of a systemic candidiasis are recurrently taken without considering the possibility of a Candida spp. biofilm-related infections. Therefore, it is important to assess the effectiveness of the available drugs and which formulations have the best performance in these specific infections. Methods: 24-h-biofilms of four Candida spp. and their response to two amphotericin B (AmB) pharmaceutical formulations (liposomal and deoxycholate) were evaluated. Results: generally, Candida glabrata was the less susceptible yeast species to both AmBs. MBECs revealed that it is therapeutically more appealing to use AmB-L than AmB-Deox for all Candida spp. biofilms, since none of the determined concentrations of AmB-L reached 10% of the maximum daily dose, but both formulations showed a very good capacity in the biomass reduction. Conclusions: the liposomal formulation presents better performance in the eradication of the biofilm cells for all the species in comparison with the deoxycholate formulation. [ABSTRACT FROM AUTHOR]

ATX-101 (deoxycholic acid) is the first pharmaceutical therapy approved by the FDA for the reduction in submental fat. Deoxycholic acid is an endogenous secondary bile acid that normally solubilizes dietary fat, contributing to its breakdown and absorption within the gut. This article reviews the identification of deoxycholic acid as a lipolytic agent, and the mechanism of action, pharmacokinetics, and pharmacodynamics of ATX-101. In addition to phase I/II trials, four Phase III clinical trials have evaluated safety and efficacy of ATX-101. These studies helped establish the appropriate dosage, administration techniques, warnings, and side effects of ATX-101. ATX-101 is effective in treating submental fat. Adverse events, although common, are mild and transient. [ABSTRACT FROM AUTHOR]

The antiinflammatory activity of purified oat 1-3,1-4-β-d-glucan against acute gastritis (sodium deoxycholate induced) model in rats was investigated as second part of experiment studying impact of oat β-glucan on inflammatory states in gastrointestinal tract (first part was related to enteritis). 48 rats (Spraque-Dawley males, two groups – control and gastritis) were fed high and low molecular weights (MW) β-glucan. Antioxidant defense parameters – SOD, TAS, GSH, GSSG and inflammation markers – TBARS, TNF-α, IL-10 and IL-12 were analyzed. Strong activity of both fractions was observed; high MW β-glucan caused high TNF-α decrease in both experimental groups while low MW β-glucan decreased the concentration of IL-10 in gastritis group. Both fractions significantly support innate antioxidant defense of stomach tissue not only in gastritis but in healthy state as well. The results reveal the potential therapeutic activity of purified oat β-glucan in acidic environment of stomach at acute gastritis states. [ABSTRACT FROM AUTHOR]

Shigella flexneri is the primary causative agent of worldwide shigellosis. As the pathogen transverses the distinct niches of the gastrointestinal tract it necessitates dynamic adaptation strategies to mitigate host antimicrobials such as dietary fatty acids (FAs) and the bile salt, deoxycholate (DOC). This study investigates the dynamics of the S. flexneri cell envelope, by interrogating adaptations following FA or DOC exposure. We deciphered the effects of FAs and DOC on bacterial membrane fatty acid and lipopolysaccharide (LPS) compositions. We identified novel LPS-based strategies by the pathogen to support resistance to these host compounds. In particular, expression of S. flexneri very-long O antigen (VL-Oag) LPS was found to play a central role in stress mitigation, as VL-Oag protects against antimicrobial FAs, but its presence rendered S. flexneri susceptible to DOC stress. Collectively, this work underpins the importance for S. flexneri to maintain appropriate regulation of cell envelope constituents, in particular VL-Oag LPS, to adequately adapt to diverse stresses during infection.

BackgroundPhosphatidylcholine (PPC) and deoxycholate (DCA) compound has been recently used for the purpose of partial lipolysis and is valued for its efficacy and lower invasiveness compared to liposuction and dermolipectomy used previously. In this article, the authors discuss the efficacy of the PPC dissolved in DCA via an experimental rat study model, along with suggesting a useful animal experimental model for the study of adipose tissue and lipolysis.MethodsBilateral inguinal fat pads of an experimental rat were elevated with the deep inferior epigastric vessel as the sole vascular pedicle. Normal saline was injected on one side as a control group and a PPC and DCA compound was injected on the other side. After 4 days, the rats were euthanized for microscopic tissue examination. The pathology was scored by a semiquantitative system in 4 categories: normal fat amount, fat necrosis, inflammatory activity, and stage of fibrosis. A Wilcoxon signed-rank test powered by SPSS packet program was used for statistical analysis and to determine significance.ResultsMicroscopic examination was performed on the obtained samples, and the experimental data of all four categories showed significant histologic differences compared to the control group. All of the data also showed statistical significance by the Wilcoxon signedrank test (P

The dichlorvos-ammonia (DV-AM) method is a simple but sensitive visual method for detecting aflatoxigenic fungi. Here we sought to develop a selective medium that is appropriate for the growth of aflatoxigenic fungi among soil mycoflora. We examined the effects of different concentrations of carbon sources (sucrose and glucose) and detergents (deoxycholate (DOC), Triton X-100, and Tween 80) on microorganisms in soils, using agar medium supplemented with chloramphenicol. The results demonstrated that 5⁻10% sucrose concentrations and 0.1⁻0.15% DOC concentrations were appropriate for the selective detection of aflatoxigenic fungi in soil. We also identified the optimal constituents of the medium on which the normal rapid growth of Rhizopus sp. was completely inhibited. By using the new medium along with the DV-AM method, we succeeded in the isolation of aflatoxigenic fungi from non-agricultural fields in Fukui city, Japan. The fungi were identified as Aspergillus nomius based on their calmodulin gene sequences. These results indicate that the new medium will be useful in practice for the detection of aflatoxigenic fungi in soil samples including those from non-agricultural environments.

[Display omitted] • Fecal bile acid (BA) analysis is an emerging area of gut microbiome research. • Sample preparation procedures for fecal BA analysis are not standardized. • After correcting for water loss fecal BA analysis from original and lyophilized results were comparable. • A single aliquot or original or lyophilized sample can be used for fecal BA analysis. Fecal bile acid (BA) analysis is an emerging area of gut microbiome research. However, sample preparation procedures for fecal BA analysis are not standardized. Current fecal BA analysis often utilizes either original or lyophilized aliquot, and fecal BA result difference between these two processing steps remains not systematically investigated. Moreover, the distribution pattern of fecal BA in the collected stool sample also remains unclear but affects interpretation of fecal BA for downstream experiments. To address these two questions regarding effect of lyophilization on fecal BA and fecal heterogeneity, fourteen separate BAs were quantified from 60 aliquots obtained from 10 clinical fecal samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). BA concentrations in the lyophilized sample were typically 2–4 folds higher than those in the original sample, but were almost identical using a water-adjusted lyophilized BA concentration. The fecal BA compositional profile and four BA ratios were similar utilizing either the original or lyophilized samples. BA concentrations were similar among different aliquots of differing starting mass except for the relatively trace-level BA. Therefore, it is suggested that fecal BA concentrations should be presented as the original sample concentration or water-adjusted lyophilization concentration to allow comparisons between studies. A single aliquot (20–100 mg) of stool can be used to reflect the concentrations in the entire sample. These results help to standardize analyses in this emerging field. [ABSTRACT FROM AUTHOR]

Phosphatidylcholine/deoxycholate (PC/DC) combination is frequently used for injection lipolysis in body contouring and size reduction of subcutaneous lipomas. Nonetheless, studies that assess possible injurious effects of PC/DC combination on tissues at injection sites are inadequate. The current work attempts to evaluate the effects of repeated PC/DC injection on skeletal muscles and neural tissues at the injection site. For this purpose, female Wistar rats were randomly assigned into 2 groups, 10 rats each, and injected percutaneously via either normal saline (control group) or PC/DC (treated group) in the groin area for 4 consecutive days. Biopsies were harvested on the 4 th day for histopathological studies. The results of the present work demonstrated that repeated injection of PC/DC caused neural damage and intense inflammation at the injection site leading to skeletal muscle degeneration, necrosis and fibrosis. Electron microscopic examination of the neural tissues in the injected area showed intra-neural fibroblasts, deposition of intra-neural collagen fibers and marked myelin degeneration. In addition, PC/DC injection caused thickening of intra-neural blood vessel walls and evident endo-neural mast cells. The current data highlight the attendant risk of neuromuscular injury associated with repeated PC/DC injection during the treatment of undesirable fat deposits and lipomas. [ABSTRACT FROM AUTHOR]

Congenital hemihyperplasia is a rare developmental disorder characterized by unilateral overgrowth of one or more body parts resulting in marked asymmetry. We are reporting here, a case of true hemifacial hypertrophy in a young female adult highlighting the clinical features and possible treatment options. [ABSTRACT FROM AUTHOR]

Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium, suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell self-propel its migration and metastasis to the bone.

Background: candidiasis is the primary fungal infection encountered in patients undergoing prolonged hospitalization, and the fourth leading cause of nosocomial bloodstream infections. One of the most important Candida spp. virulence factors is the ability to form biofilms, which are extremely refractory to antimicrobial therapy and very difficult to treat with the traditional antifungal therapies. It is known that the prophylaxis or treatment of a systemic candidiasis are recurrently taken without considering the possibility of a Candida spp. biofilm-related infections. Therefore, it is important to assess the effectiveness of the available drugs and which formulations have the best performance in these specific infections. Methods: 24-h-biofilms of four Candida spp. and their response to two amphotericin B (AmB) pharmaceutical formulations (liposomal and deoxycholate) were evaluated. Results: generally, Candida glabrata was the less susceptible yeast species to both AmBs. MBECs revealed that it is therapeutically more appealing to use AmB-L than AmB-Deox for all Candida spp. biofilms, since none of the determined concentrations of AmB-L reached 10% of the maximum daily dose, but both formulations showed a very good capacity in the biomass reduction. Conclusions: the liposomal formulation presents better performance in the eradication of the biofilm cells for all the species in comparison with the deoxycholate formulation.

'Manda Koso' is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (-88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet. [ABSTRACT FROM AUTHOR]

Plastein is a thixotropic product of protease-induced peptide aggregation. This study evaluated the effects of the modified peptide structure of plastein on its affinity for a secondary bile acid. Casein plastein formation resulted in decreased free amino nitrogen and increased mean particle size, surface hydrophobicity and hydrophobic-to-hydrophilic amino acid ratio of the peptides. The net negative surface charge of casein hydrolysate (CH) was decreased ( P  < 0.05) in crude plastein (CPc) and completely lost in the isolated plastein (CPi) resulting in the formation of insoluble aggregates. The surface and structural changes in CPi were associated with 38.5 ± 0.0% binding of physiological level of sodium deoxycholate, higher ( P  < 0.05) than the activities of CPc (23.1 ± 0.0%) and CH (12.8 ± 4.4%). Maximum specific ligand binding (B max ) was higher ( P  < 0.05) for CPc (0.391 ± 0.021 mM/mg protein) than CH (0.246 ± 0.043 mM/mg protein) and CPi (0.234 ± 0.005 mM/mg protein). However, CPi had the strongest affinity for sodium deoxycholate with the lowest dissociation constant (K d ) of 2.719 ± 0.146 mM, which was 2.5- and 3-folds lower ( P  < 0.05) than those of CH and CPc, respectively. Understanding deoxycholate-binding affinity of peptides can facilitate the design of potent food-based BA sequestrants for managing hypercholesterolaemia (dyslipidaemia) and associated health conditions. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is a hydrophobic polyene antibiotic used in the therapy of systemic fungal infections. Due to its poor water solubility, it is formulated as a colloidal suspension for intravenous administration using deoxycholate as the solubilizing agent (Fungizone). However, severe toxicity of the formulation has prompted the development of more efficient and safer delivery agents. Gemini amino acid-based surfactants constitute a promising alternative to the biological bile salt surfactant(s), as both biocompatible and biodegradable drug carriers. The supramolecular behaviour of an anionic gemini surfactant derived from cysteine, (C 8 Cys) 2 , was characterized by tensiometry and its solubilization capability towards the hydrophobic drug AmB was evaluated under biomimetic conditions (phosphate buffered-saline, pH 7.4). Important aggregation parameters, such as critical micelle concentration (CMC), surface tension at the CMC ( γ cmc ), maximum surface excess concentration ( Γ max ) and minimum area occupied per molecule at the water/air interface ( A min ) were determined. Solubilization power was quantified in terms of molar solubilization ratio ( χ ), micelle-water partition coefficient ( K p ) and Gibbs energy of solubilization ( Δ G s 0 ) . The aggregation state of AmB in the micellar media was assayed by UV–Vis spectroscopy and in vitro antifungal activity was evaluated. Results were compared with the ones obtained for sodium deoxycholate (NaDC) and discussed in terms of drug loading, efficacy and efficiency. Complementary rheological measurements were performed as NaDC solutions formed a shear-thinning gel at concentrations of 0.01 mol L −1 and higher, in the experimental conditions employed. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the leading causes of cancer deaths. It correlates to a high fat diet, which causes an increase of the secondary bile acids including deoxycholate (DOC) in the intestine. We aimed to determine the effects of DOC on intestinal carcinogenesis in Apc mice, a model of spontaneous intestinal adenomas. Four-week old Apc mice were treated with 0.2 % DOC in drinking water for 12 weeks. The number and size of tumors were measured, and tissue sections were prepared for the evaluation of intestinal carcinogenesis, cell proliferation, and apoptosis. The activation of Wnt signaling was detected in the intestinal tumor cells of the Apc mice, and also in the human colon samples. DOC increased the number of intestine tumors by 165.1 % compared with that in untreated Apc mice mainly in the middle and distal segments of the small intestine and colon. The numbers of all sizes of tumors in the small intestine were increased. Intestinal carcinogenesis was confirmed in 75 % mice in DOC treated- Apc mice compared with 0 % in untreated mice. This was accompanied by promoting tumor cell proliferation and decreasing apoptosis, and increasing the percentage of β-catenin positive cells and its nuclear expression in intestinal tumor cells of Apc mice, and also up-regulating the expression of cyclin D1. In addition, the activation of Wnt signaling also played in modulating human colon carcinogenesis. Our studies suggest that DOC enhances the multiplicity of intestinal tumor, and accelerates intestinal adenoma-adenocarcinoma sequence in Apc mice mediated by stimulating tumor cell proliferation and decreasing apoptosis through enhancing Wnt signaling. [ABSTRACT FROM AUTHOR]