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1.
Int Braz J Urol ; 50(6): 781-782, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39226447

RESUMEN

PURPOSE: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. MATERIALS AND METHODS: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. RESULTS: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. CONCLUSIONS: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.


Asunto(s)
Íleon , Procedimientos Quirúrgicos Robotizados , Uréter , Obstrucción Ureteral , Humanos , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Uréter/cirugía , Íleon/cirugía , Resultado del Tratamiento , Obstrucción Ureteral/cirugía , Constricción Patológica/cirugía , Tempo Operativo , Anastomosis Quirúrgica/métodos , Procedimientos Quirúrgicos Urológicos/métodos
2.
Cancer Med ; 13(17): e70229, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39267462

RESUMEN

BACKGROUND: Benign uretero-ileal anastomotic stricture (UIAS) is a potentially serious complication that can arise after radical cystectomy (RC) and subsequent urinary diversion. To preserve residual renal function and improve prognosis, it is crucial to derive insights from experience and tailor individualized treatment strategies for different patients. PATIENTS AND METHODS: From October 2014 to June 2021, a total of 47 patients with benign UIAS underwent endoscopic management (n = 19) or reimplantation surgery (n = 28). The basic data, perioperative conditions, and postoperative outcomes of the two groups were compared and analyzed to evaluate efficacy. RESULTS: Comparing preoperative and postoperative clinical efficacy within the same group, the endoscopic group showed no significant differences in creatinine and blood urea nitrogen (BUN) levels before surgery or after extubation (p > 0.05). However, significant differences were observed in glomerular filtration rate (GFR) levels on the affected side before surgery and after extubation (p < 0.05). In contrast, the laparoscopic reimplantation group did not exhibit significant differences in creatinine, BUN, or GFR levels of affected side before surgery and after extubation (p > 0.05). Postoperative clinical efficacy showed no significant difference in creatinine and BUN levels between the two groups (p > 0.05). However, GFR values of affected side in the endoscopic treatment group decreased more than those in the laparoscopic reimplantation group (p < 0.05). Additionally, the laparoscopic reimplantation group was able to remove the single-J tube earlier than the endoscopic treatment group (p < 0.05), had a lower recurrence rate of hydronephrosis after extubation (p < 0.05), and experienced a later onset of hydronephrosis compared to the endoscopic treatment group (p < 0.05). CONCLUSIONS: Based on our experience in treating UIAS following RC combined with urinary diversion, laparoscopic reimplantation effectively addresses the issue of UIAS, allowing for the removal of the ureteral stent relatively soon after surgery. This approach maintains long-term ureteral patency, preserves residual renal function, reduces the risk of ureteral restenosis and hydronephrosis, and has demonstrated superior therapeutic outcomes in this study.


Asunto(s)
Anastomosis Quirúrgica , Cistectomía , Complicaciones Posoperatorias , Uréter , Derivación Urinaria , Humanos , Derivación Urinaria/efectos adversos , Derivación Urinaria/métodos , Cistectomía/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Constricción Patológica/etiología , Constricción Patológica/cirugía , Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Uréter/cirugía , Tasa de Filtración Glomerular , Íleon/cirugía , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Resultado del Tratamiento , Creatinina/sangre , Laparoscopía/efectos adversos , Obstrucción Ureteral/cirugía , Obstrucción Ureteral/etiología
3.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39273567

RESUMEN

Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium, Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.


Asunto(s)
Biomarcadores , Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Medicina de Precisión , Humanos , Disbiosis/microbiología , Niño , Femenino , Masculino , Enfermedades Inflamatorias del Intestino/microbiología , Adolescente , Medicina de Precisión/métodos , ARN Ribosómico 16S/genética , Heces/microbiología , Preescolar , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Íleon/microbiología , Íleon/patología , Colitis Ulcerosa/microbiología
6.
Gut Microbes ; 16(1): 2390176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39205654

RESUMEN

Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.


Asunto(s)
Ácidos y Sales Biliares , Colestasis , Microbioma Gastrointestinal , Lactobacillus acidophilus , Hígado , Ratones Endogámicos C57BL , Probióticos , Ácidos y Sales Biliares/metabolismo , Animales , Colestasis/metabolismo , Colestasis/microbiología , Ratones , Humanos , Masculino , Probióticos/farmacología , Probióticos/administración & dosificación , Hígado/metabolismo , Heces/microbiología , Colesterol 7-alfa-Hidroxilasa/metabolismo , Colesterol 7-alfa-Hidroxilasa/genética , Femenino , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Trasplante de Microbiota Fecal , Disbiosis/microbiología , Disbiosis/terapia , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Adulto , Modelos Animales de Enfermedad , Íleon/microbiología , Íleon/metabolismo
7.
Int J Mol Sci ; 25(16)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39201512

RESUMEN

Crohn's disease (CD) is frequently complicated by strictures that can be either inflammatory or fibrostenotic. This distinction is important for deciding the best treatment course, but it can be difficult to determine clinically, sometimes even by advanced imaging techniques. We performed miRNA PCR panel screening on pooled samples of ileum with CD fibrostenosis or inflammatory stenosis. Eight miRNAs with profibrotic (miR-93-5p, miR-376c-3p and miR-424-5p), or fibroprotective (miR-133a-3p, miR-133b, miR-193a-5p, miR-335-5p and miR-378a-3p) functions described in the literature were selected for validation on 20 samples each of CD with fibrostenosis or inflammatory stenosis, with a separate sampling of the submucosa and subserosa. The results showed significant differences between the groups in subserosal samples, with upregulation of profibrotic miRNAs and downregulation of fibroprotective miRNAs in fibrostenosis compared to inflammatory stenosis. Only miR-424-5p showed a significant difference in the submucosa. There were significant differences in miRNA expression between subserosa and submucosa. Our results provide further evidence that the major differences between fibrostenosis and inflammatory stenosis are located in the subserosa, which is inaccessible to endoscopic sampling, highlighting the need for cross-sectional imaging or serological markers. We identify several miRNAs previously not connected to fibrosis in CD, which could potentially serve as biomarkers of fibrostenosis.


Asunto(s)
Enfermedad de Crohn , Fibrosis , MicroARNs , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Enfermedad de Crohn/metabolismo , Humanos , MicroARNs/genética , Fibrosis/genética , Masculino , Constricción Patológica/genética , Adulto , Femenino , Persona de Mediana Edad , Íleon/metabolismo , Íleon/patología , Regulación de la Expresión Génica , Perfilación de la Expresión Génica
8.
Ann Ital Chir ; 95(4): 603-608, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39186356

RESUMEN

AIM: This work investigated the effect of an abdominal corset on the colonoscopy completion rate, as well as cecum and ileum intubation time, total colonoscopy time, and pain score in centrally obese patients. METHODS: Patients were randomized into two groups, with 50 patients in each group. A colonoscopy was performed using the abdominal corset in Group 1 and the standard method in Group 2. The comparison between the groups evaluated demographic data, procedure details, circulatory dynamics, anesthesia data, and visual analogue scale (VAS). RESULTS: Of the patients included in the study, 60 were female, and 40 were male, with a mean age of 57.3 ± 13.6 years. Cecal intubation time (Z: -2.66 p: 0.008), total colonoscopy time (Z: -2.180 p: 0.029), number of maneuvers (χ2: 8.391 p: 0.039), and VAS (Z: -3.087 p: 0.002) were significantly lower in the abdominal corset group. CONCLUSIONS: An abdominal corset that applies external abdominal compression reduces the cecal intubation time, the total colonoscopy time, the number of maneuvers, and the pain level. CLINICAL TRIAL REGISTRATION: NCT03128645 (https://clinicaltrials.gov/study/NCT03128645?tab=results).


Asunto(s)
Ciego , Colonoscopía , Obesidad Abdominal , Humanos , Femenino , Masculino , Persona de Mediana Edad , Colonoscopía/métodos , Estudios Prospectivos , Obesidad Abdominal/complicaciones , Íleon , Anciano , Factores de Tiempo , Intubación Gastrointestinal , Adulto , Dimensión del Dolor , Tempo Operativo
9.
J Anim Sci ; 1022024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-39113375

RESUMEN

A total of 480 newly weaned pigs (PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ±â€…0.61 kg were used in a dose-response study to investigate the impact of increasing standardized ileal digestible (SID) Arg:Lys on nursery pig growth performance. At weaning, pigs were placed into 48 pens with 5 barrows and 5 gilts per pen. Pens were randomly assigned to 1 of 6 dietary treatments. The experimental diets were formulated with increasing SID Arg:Lys, achieved by substituting corn starch, glycine, and l-alanine with l-arginine, resulting in SID Arg:Lys ranging from 45% to 145%. Diets were sublimiting in SID Lys and exceeded all other essential amino acid requirements. The experimental diets were fed across two feeding phases from days 0 to 10 and 10 to 27, with adjustments made to account for the Lys requirement of the pigs. All pens were placed on a common diet for the remaining 14 d of the study to evaluate carryover effects. Pigs and feeders were weighed at the start and end of each phase to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed according to a linear regression model, which included the linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.50 < P ≤ 0.10. From days 0 to 27, Arg:Lys tended to have a quadratic effect on ADFI (P = 0.058), where 97.00 ±â€…7.631% SID Arg:Lys maximized feed intake. Similarly, Arg:Lys had a quadratic impact on ADG (P = 0.046), where ADG was maximized at a SID Arg:Lys of 95.65 ±â€…7.165. Correspondingly, Arg:Lys had a quadratic effect on pig BW on day 27 (P = 0.014). These effects were carried through the end of the study, where Arg:Lys quadratically impacted days 0 to 41 ADFI (P = 0.006), ADG (P = 0.077), and day 41 BW (P = 0.028). There was no evidence of an effect of SID Arg:Lys on G:F throughout the study (P ≥ 0.315). In conclusion, SID Arg:Lys quadratically impacted ADFI and ADG in 6- to 13-kg nursery pigs, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]), and ADG was maximized at a SID Arg:Lys of 95.65% (95% CI [81.2%, 110.1%]). Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is at least 81%, based on the lower bounds of the 95% CI for maximum ADG and ADFI, and excessive Arg supplementation may negatively affect growth performance.


Arginine is considered a conditionally essential amino acid (EAA) in swine, meaning that under certain circumstances, the rate of Arg utilization is greater than endogenous synthesis, resulting in a dietary Arg requirement to meet the pig's needs for growth and other biological functions. Our group and others have shown benefits to feeding Arg levels above the NRC (2012) estimated requirement; however, there has been a lack of research to determine the SID Arg requirement relative to lysine in young pigs. Therefore, the objective of this study was to determine the optimal dietary SID Arg:Lys to maximize growth performance in 6- to 13-kg nursery pigs. In the current trial, average daily gain (ADG) and average daily feed intake (ADFI) responded quadratically to increasing SID Arg:Lys from 45% to 145%, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]) and ADG was maximized at 95.65% (95% CI [81.2%, 110.1%]). Together, the results of this study suggest the SID Arg:Lys requirement of 6- to 13-kg nursery pigs is at least 81%, based on the lower bounds of the 95% confidence intervals for maximum ADG and ADFI, but excess supplementation may reduce performance.


Asunto(s)
Alimentación Animal , Fenómenos Fisiológicos Nutricionales de los Animales , Arginina , Dieta , Lisina , Animales , Arginina/farmacología , Arginina/administración & dosificación , Dieta/veterinaria , Alimentación Animal/análisis , Lisina/administración & dosificación , Lisina/farmacología , Masculino , Femenino , Porcinos/crecimiento & desarrollo , Porcinos/fisiología , Íleon/fisiología , Íleon/efectos de los fármacos , Digestión/efectos de los fármacos , Distribución Aleatoria , Suplementos Dietéticos/análisis , Aumento de Peso/efectos de los fármacos
10.
FEMS Microbiol Ecol ; 100(9)2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39169462

RESUMEN

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.


Asunto(s)
Candida , Disbiosis , Microbioma Gastrointestinal , Íleon , Humanos , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Íleon/microbiología , Íleon/efectos de los fármacos , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/microbiología , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Modelos Biológicos , Mucosa Intestinal/microbiología
11.
Phytomedicine ; 133: 155924, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39098169

RESUMEN

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a critical stage in the progression of non-alcoholic fatty liver disease (NAFLD), characterized by obvious inflammation and fibrosis. Because of its high incidence rate and serious consequences, NASH is becoming a global health problem. The influence of endotoxin translocation on NASH is receiving attention. As a traditional Chinese herb that effectively improves hepatic inflammation, Fructus Aurantii (Quzhou origin, FAQ) is widely used in the clinical treatment of NASH. However, the intervention mechanism of FAQ on reg3g and related endotoxin translocation remains unclear. AIM: To study the mechanism of the impact by which ileal regenerating family member 3 gamma (reg3g) deficiency and subsequent endotoxin translocation impact the progression of NASH; To elucidate the efficacy and mechanism of FAQ in the treatment of NASH. METHODS: Clinical serum, ileal tissue, and dynamic NASH model-related analyses collectively confirmed that reg3g is a pivotal gene associated with NASH. Reg3g-/- mice were used to assess the impact of reg3g on liver injury, inflammation, and fibrosis, as well as the underlying mechanism involved. In vitro studies elucidated the regulatory effects of FAQ on reg3g, intestinal barrier function, and intestinal permeability. Subsequently, the efficacy of FAQ was investigated in NASH mouse models. Pathological examinations combined with Western blotting (WB), immunohistochemistry (IHC), and multiplex immunohistochemical (mIHC) analyses were used to evaluate the effects of FAQ on mucosal repair and barrier function. Transepithelial electrical resistance (TEER), fluorescein isothiocyanate-dextran 4 (FD-4) experiments, coupled with enzyme linked immunosorbent assay (ELISA) and chromogenic LAL endotoxin assay were used to confirm intestinal permeability and endotoxin translocation. The results of WB and mIHC reflected the levels of endotoxin recruitment and M1 macrophage polarization in the liver. Parameters such as body weight, transaminases, and cholesterol were utilized to assess the metabolic effects of FAQ. RESULTS: Decreased expression of reg3g was associated with the progression of NASH. Ileal deficiency in reg3g resulted in damage to the intestinal barrier and permeability, leading to the recruitment of endotoxins via the 'gut-liver' axis to the liver, causing the polarization of M1 macrophages, release of inflammatory factors, excessive inflammation, and activation of hepatic stellate cells (HSCs), leading to fibrosis. FAQ significantly upregulated ileal reg3g expression and the expression of intestinal barrier-related proteins tight junction protein 1 (ZO-1) and occludin (OLCN) in mice (p < 0.05), thereby improving intestinal barrier function and permeability. Reduced intestinal permeability led to decreases in endotoxins entering the bloodstream and accumulating in the liver (p < 0.05). The expression of CD68 suggested reduced polarization of M1 macrophages. Expression levels of actin alpha 2, smooth muscle actin (α-SMA) and extracellular matrix (ECM)-related proteins also decreased, indicating improved liver fibrosis. CONCLUSION: FAQ ameliorates NASH by upregulating the expression of reg3g. The upregulation of reg3g contributes to the repair of the intestinal barrier and permeability, reducing the recruitment of endotoxins and subsequent polarization of M1 macrophages, excessive inflammation, and fibrosis.


Asunto(s)
Medicamentos Herbarios Chinos , Íleon , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Proteínas Asociadas a Pancreatitis , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Ratones , Masculino , Humanos , Íleon/efectos de los fármacos , Íleon/metabolismo , Medicamentos Herbarios Chinos/farmacología , Modelos Animales de Enfermedad , Ratones Noqueados , Hígado/efectos de los fármacos , Hígado/metabolismo , Endotoxinas
12.
Gene ; 931: 148872, 2024 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-39159791

RESUMEN

BACKGROUND: Crohn's disease (CD) is marked by disruption of intestinal epithelial barrier, with unclear underlying molecular mechanisms. This study aimed to investigate key genes regulating the intestinal barrier in CD patients. METHODS: Differential gene expression analysis and gene set enrichment analysis were conducted to identify potential key genes involved in CD within the GEO database. Single-cell RNA sequencing from ileum samples in GSE134809 of 59,831 inflamed and uninflamed cells from 11 CD patients and microarray data from ileal tissues in GSE69762 (3 controls and 4 CD patients) and GSE75214 (11 controls and 51 CD patients) with GSE179285 (49 uninflamed and 33 inflamed from CD patients) as the validation set. Protein-protein interaction and logistic regression analyses identified key downregulated genes in CD. A key gene was then investigated through immunohistochemistry of ileal tissues from 5 CD patients and in the Caco-2 cell line with RNA interference and treatment with IFN-γ and TNF-α to stimulate inflammation. RESULTS: Single-cell RNA-seq identified 33 genes and microarray identified 167 genes with significant downregulation in inflamed CD samples. PCK1 was identified and validated as one of the most promising candidate genes. Reduced PCK1 expression was evident in inflamed ileal tissues. In vitro, knockdown of PCK1 resulted in decreased cell viability, increased apoptosis, and reduced nectin-2 production, while combination of IFN-γ and TNF-α significantly reduced PCK1. CONCLUSIONS: PCK1 is downregulated in inflamed ileal tissues of CD patients and may be a key factor in maintaining epithelial integrity during inflammation in Crohn's disease.


Asunto(s)
Enfermedad de Crohn , Íleon , Mucosa Intestinal , Humanos , Enfermedad de Crohn/genética , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Íleon/metabolismo , Íleon/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Células CACO-2 , Masculino , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Femenino , Adulto , Apoptosis/genética , Regulación hacia Abajo , Análisis de la Célula Individual , Perfilación de la Expresión Génica
13.
Food Funct ; 15(17): 8775-8787, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39105499

RESUMEN

The consumption of complementary foods can bring about diarrhea and intestinal barrier dysfunction in infants. In this study, three different Lactobacillus strains combined with L-tryptophan (Trp) were administered to rat pups with complementary foods. Complementary food feeding caused inflammatory cell infiltration, crypt structure irregularity and goblet cell reduction in the colon tissues of the rat pups. However, the oral administration of Trp combined with Lactiplantibacillus plantarum DPUL-S164 or Limosilactobacillus reuteri DPUL-M94 significantly restored the pathological changes in the colon tissues and inhibited the expression of pro-inflammatory cytokines in the colon and ileum of the rat pups. M94 or S164 combined with Trp intervention could promote the expression of cell differentiation genes and tight junction proteins, and restore the intestinal barrier damage caused by complementary foods in rat pups by activating the aryl hydrocarbon receptors (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In addition, the indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), or indole-3-carbaldehyde (I3C) level in the cecal contents of the rat pups increased after intervention of Trp combined with S164 or M94, which may account for the amelioration of intestinal barrier damage in rat pups administered with complementary foods. Furthermore, S164 or M94 combined with Trp intervention up-regulated the relative abundance of f_Lactobacillaceae, f_Akkermansiaceae, g_Lactobacillus, and g_Akkermansia in the intestinal tract of the rat pups. In conclusion, S164 or M94 combined with Trp intervention can ameliorate complementary food-induced intestinal barrier damage and gut flora disorder in rat pups by producing ILA, IPA, or I3C, which are AhR ligands.


Asunto(s)
Indoles , Mucosa Intestinal , Ratas Sprague-Dawley , Triptófano , Animales , Ratas , Indoles/farmacología , Triptófano/farmacología , Triptófano/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Lactobacillus , Probióticos/farmacología , Probióticos/administración & dosificación , Colon/metabolismo , Colon/microbiología , Colon/patología , Masculino , Limosilactobacillus reuteri , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Receptores de Hidrocarburo de Aril/metabolismo , Íleon/metabolismo , Íleon/microbiología , Íleon/efectos de los fármacos
14.
J Med Case Rep ; 18(1): 357, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39103938

RESUMEN

BACKGROUND: Heterotopic gastric mucosa (HGM) can be located in various parts of the gastrointestinal tract. As a rare anomaly in the small intestine, it can become complicated by intussusception, obstruction, gastrointestinal bleeding, and even peritonitis, leading to death. CASE PRESENTATION: This case report focuses on a 12-year-old Middle Eastern boy who presented with hematochezia and abdominal pain for a couple of days. A tagged Red blood cell (RBC) scan and Technetium scan revealed gastrointestinal bleeding at the lower abdomen, highly suggestive of the diagnosis of Meckel's diverticulum. Subsequently, exploratory laparotomy revealed contiguous and scattered mucosal lesions with multiple polyps of various sizes in the terminal ileum. Meckel's diverticulum was absent, and the patient was treated with resection and primary anastomosis. The resected tissue revealed extensive ectopic gastric mucosa and polypoid tissues. The patient recovered uneventfully and was discharged four days after the surgery. The symptoms did not recur within six months after his surgery. CONCLUSION: Our case demonstrated that despite the rarity of multiple polypoid gastric heterotopias in the terminal ileum, it should be considered as one of the differential diagnoses of gastrointestinal tract bleeding.


Asunto(s)
Coristoma , Mucosa Gástrica , Hemorragia Gastrointestinal , Divertículo Ileal , Humanos , Masculino , Hemorragia Gastrointestinal/etiología , Mucosa Gástrica/patología , Coristoma/complicaciones , Coristoma/cirugía , Coristoma/patología , Divertículo Ileal/complicaciones , Divertículo Ileal/cirugía , Niño , Enfermedades del Íleon/cirugía , Enfermedades del Íleon/etiología , Diagnóstico Diferencial , Íleon/patología , Íleon/cirugía , Íleon/diagnóstico por imagen , Dolor Abdominal/etiología , Resultado del Tratamiento
15.
Microb Pathog ; 195: 106852, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39147213

RESUMEN

The purpose of this study was to evaluate the ability of Bacillus subtilis JATP3 to stimulate immune response and improve intestinal health in piglets during the critical weaning period. Twelve 28-day-old weaned piglets were randomly divided into two groups. One group was fed a basal diet, while the other group was fed a basal diet supplemented with B. subtilis JATP3 (1 × 109 CFU/mL; 10 mL) for 28 days. The results revealed a significant increase in the intestinal villus gland ratio of weaned piglets following the inclusion of B. subtilis JATP3 (P < 0.05). Inclusion of a probiotic supplement improve the intestinal flora of jejunum and ileum of weaned piglets. Metabolomics analysis demonstrated a notable rise in citalopram levels in the jejunum and ileum, along with elevated levels of isobutyric acid and isocitric acid in the ileum. The results of correlation analysis show that indicated a positive correlation between citalopram and microbial changes. Furthermore, the probiotic-treated group exhibited a significant upregulation in the relative expression of Claudin, Zonula Occludens 1 (ZO-1), and Interleukin 10 (IL-10) in the jejunum and ileum, while displaying a noteworthy reduction in the relative expression of Interleukin 1ß (IL-1ß). Overall, these findings suggest that B. subtilis JATP3 can safeguard intestinal health by modulating the structure of the intestinal microbiota and their metabolites, wherein citalopram might be a key component contributing to the therapeutic effects of B. subtilis JATP3.


Asunto(s)
Bacillus subtilis , Citalopram , Microbioma Gastrointestinal , Íleon , Yeyuno , Probióticos , Destete , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Bacillus subtilis/metabolismo , Porcinos , Probióticos/administración & dosificación , Probióticos/farmacología , Íleon/microbiología , Íleon/inmunología , Citalopram/farmacología , Yeyuno/microbiología , Yeyuno/inmunología , Yeyuno/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Metabolómica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Proteína de la Zonula Occludens-1/metabolismo , Suplementos Dietéticos
16.
Expert Opin Pharmacother ; 25(12): 1647-1655, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39155775

RESUMEN

INTRODUCTION: Alagille syndrome (ALGS) is a rare, genetic, multisystem disorder commonly associated with cholestatic liver disease; patients with ALGS may experience elevated serum bile acids and severe pruritus with associated impaired sleep. The ileal bile acid transporter (IBAT) is located on the luminal surface of enterocytes in the terminal ileum; this transport protein mediates resorption of conjugated bile acids for recirculation back to the liver. Inhibition of IBAT disrupts the enterohepatic circulation and leads to fecal elimination of bile acids. AREAS COVERED: Here, the role of odevixibat as a novel, nonsurgical approach to interrupting the enterohepatic circulation from the intestine by inhibition of IBAT is reviewed, specifically in reference to currently available data on pharmacologic IBAT inhibition. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of cholestatic liver diseases in children including ALGS. EXPERT OPINION: Odevixibat or IBAT inhibitor should be considered as a first-line treatment for ALGS to improve pruritis, quality of life and liver-related outcomes including absence of liver transplant, surgical biliary diversion, hepatic decompensation, and death.


Asunto(s)
Síndrome de Alagille , Ácidos y Sales Biliares , Humanos , Síndrome de Alagille/tratamiento farmacológico , Ácidos y Sales Biliares/metabolismo , Prurito/tratamiento farmacológico , Prurito/etiología , Animales , Niño , Íleon/efectos de los fármacos , Íleon/metabolismo , Metilaminas , Tiazepinas
17.
Biol Pharm Bull ; 47(8): 1429-1436, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135238

RESUMEN

Farnesoid X receptor (FXR) is a nuclear receptor that regulates the synthesis and enterohepatic circulation of bile acids (BAs). It also regulates lipid and carbohydrate metabolism, making FXR ligands potential therapeutic agents for systemic and/or hepatic metabolic disorders. We previously synthesized a series of FXR antagonists and showed that oral administration of FLG249 reduced the expression of several FXR target genes in the mouse ileum. Here, we investigated the effects of FLG249 on lipid metabolism in mice fed a high-fat diet (HFD). When FLG249 was administered for 4 weeks to HFD-induced obese mice, it altered the expression of genes related to BA metabolism, ceramide synthesis and fatty acid ß-oxidation, improving lipid metabolism in the liver and ileum without decreasing body weight. These findings suggest that FLG249 has the potential to be a low toxicity pharmaceutical compound and likely acts as a nonsteroidal FXR antagonist to improve lipid metabolism disorders.


Asunto(s)
Colesterol , Dieta Alta en Grasa , Hígado , Ratones Endogámicos C57BL , Obesidad , Receptores Citoplasmáticos y Nucleares , Triglicéridos , Animales , Dieta Alta en Grasa/efectos adversos , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Receptores Citoplasmáticos y Nucleares/metabolismo , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/sangre , Colesterol/sangre , Triglicéridos/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Ácidos y Sales Biliares/metabolismo , Ratones , Ratones Obesos , Íleon/metabolismo , Íleon/efectos de los fármacos
18.
Turk J Gastroenterol ; 35(8): 609-617, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-39150326

RESUMEN

Terminal ileal ulcers can have various etiologies, including Crohn's disease (CD), infections, and medication-related causes. This study aims to investigate the incidence of terminal ileal ulcers detected during colonoscopies, explore their underlying causes, and analyze their clinical, endoscopic, and histopathological characteristics. Additionally, the study aims to identify predictive factors that indicate the need for follow-up. Medical records of all patients who underwent colonoscopies, between 2009 and 2019 were retrospectively reviewed. Patients with terminal ileal ulcers, with or without ileocecal valve involvement, were included in the study. Demographic information, medication usage, symptoms, colonoscopy findings, and histopathological data of these patients were analyzed. A total of 398 patients were included in the study. Histopathological examination revealed that 243 patients (61%) had active ileitis, and 69 patients (17.4%) had chronic active ileitis. The final diagnoses for ulcers were: nonspecific ulcers in 212 patients (53.3%), CD in 66 patients (16.6%), and non-steroidal anti-inflammatory drug-induced ulcers in 58 patients (14.6%). In the multivariate analysis, the parameters predicting CD included the presence of 10 or more ulcers (odds ratio (OR) = 7.305), deep ulcers (OR = 7.431), and edematous surrounding tissue (OR = 5.174), all of which were statistically significant (P < .001). Upon final evaluation, only 66 patients (16.6%) were diagnosed with CD, while 212 patients (53.3%) had nonspecific ulcers. The majority of patients with healed ulcers exhibited pathological findings consistent with active ileitis. Therefore, it can be concluded that not all terminal ileal ulcers are indicative of CD. In those cases with active ileitis, repetitive colonoscopies should be reconsidered.


Asunto(s)
Colonoscopía , Enfermedad de Crohn , Enfermedades del Íleon , Ileítis , Úlcera , Humanos , Estudios Retrospectivos , Femenino , Masculino , Úlcera/etiología , Úlcera/patología , Adulto , Persona de Mediana Edad , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/patología , Enfermedades del Íleon/etiología , Enfermedades del Íleon/patología , Ileítis/etiología , Ileítis/patología , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Adulto Joven , Íleon/patología , Incidencia , Adolescente
20.
Tech Coloproctol ; 28(1): 116, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198315

RESUMEN

BACKGROUND: Surgery for Crohn's disease (CD) is considered to have more complications due to the underlying inflammation, immunosuppression, and malnutrition. We sought to study the outcomes of right-sided colonic resection in patients with CD and patients with cancer at a high-volume tertiary center utilizing a standardized perioperative protocol. METHODS: This is a retrospective study of outcomes for all patients with CD or patients undergoing ileocolic resection or right hemicolectomy with ileocolic anastomosis at a single institution from 2013 to 2022. Patients were excluded if they simultaneously underwent another procedure or ostomy creation. Data were analyzed using Wilcoxon rank-sum and chi-squared tests for univariate analyses, and logistic and linear regressions for multivariate analyses. RESULTS: In total 141 patients with CD and 589 patients with cancer were included. Patients with CD were significantly younger with lower body mass index and less likely to have comorbidities, including diabetes and hypertension. Patients with CD were less likely to have a smoking history or prior abdominal surgery, but more likely to be on steroids. Both groups had similar rates of laparoscopy, intraoperative complications, and blood loss. Despite the preoperative and intraoperative differences, both patients with CD and patients with cancer had similar lengths of stay (LOS), readmission, reoperation, and mortality rates. None of the surgical outcomes differed significantly between the two groups. On multivariate analysis, CD diagnosis was not associated with reoperation, readmission, mortality, or LOS while controlling for other characteristics. CONCLUSIONS: With the use of standardized perioperative protocols, surgery for CD at a high-volume center with expertise in CD can be performed with comparable results to other indications like cancer.


Asunto(s)
Colectomía , Enfermedad de Crohn , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Colectomía/efectos adversos , Colectomía/métodos , Adulto , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anciano , Colon/cirugía , Neoplasias del Colon/cirugía , Neoplasias del Colon/mortalidad , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Readmisión del Paciente/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Íleon/cirugía , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Laparoscopía/efectos adversos , Complicaciones Intraoperatorias/etiología
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