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1.
J Exerc Sci Fit ; 22(4): 297-304, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38706951

ABSTRACT

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P<0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P<0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P<0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P<0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

2.
ACS Catal ; 14(9): 6650-6658, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38721379

ABSTRACT

Arginine phosphorylation plays numerous roles throughout biology. Arginine kinase (AK) catalyzes the delivery of an anionic phosphoryl group (PO3-) from ATP to a planar, trigonal nitrogen in a guanidinium cation. Density functional theory (DFT) calculations have yielded a model of the transition state (TS) for the AK-catalyzed reaction. They reveal a network of over 50 hydrogen bonds that delivers unprecedented pyramidalization and out-of-plane polarization of the arginine guanidinium nitrogen (Nη2) and aligns the electron density on Nη2 with the scissile P-O bond, leading to in-line phosphoryl transfer via an associative mechanism. In the reverse reaction, the hydrogen-bonding network enforces the conformational distortion of a bound phosphoarginine substrate to increase the basicity of Nη2. This enables Nη2 protonation, which triggers PO3- migration to generate ATP. This polarization-pyramidalization of nitrogen in the arginine side chain is likely a general phenomenon that is exploited by many classes of enzymes mediating the post-translational modification of arginine.

3.
Biomed Environ Sci ; 37(4): 399-405, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38727162

ABSTRACT

Objective: This study aimed to determine the current epidemiological status of PLWHA aged ≥ 50 years in China from 2018 to 2021. It also aimed to recommend targeted interventions for the prevention and treatment of HIV/AIDS in elderly patients. Methods: Data on newly reported cases of PLWHA, aged ≥ 50 years in China from 2018 to 2021, were collected using the CRIMS. Trend tests and spatial analyses were also conducted. Results: Between 2018 and 2021, 237,724 HIV/AIDS cases were reported among patients aged ≥ 50 years in China. The main transmission route was heterosexual transmission (91.24%). Commercial heterosexual transmission (CHC) was the primary mode of transmission among males, while non-marital non-CHC ([NMNCHC]; 60.59%) was the prevalent route in women. The proportion of patients with CHC decreased over time ( Z = 67.716, P < 0.01), while that of patients with NMNCHC increased ( Z = 153.05, P < 0.01). The sex ratio varied among the different modes of infection, and it peaked at 17.65 for CHC. The spatial analysis indicated spatial clustering, and the high-high clustering areas were mainly distributed in the southwestern and central-southern provinces. Conclusion: In China, PLWHA, aged ≥ 50 years, were predominantly infected through heterosexual transmission. The primary modes of infection were CHC and NMNCHC. There were variations in the sex ratio among different age groups, infected through various sexual behaviors. HIV/AIDS cases exhibited spatial clustering. Based on these results, the expansion of HIV testing, treatment, and integrated behavioral interventions in high-risk populations is recommended to enhance disease detection in key regions.


Subject(s)
Acquired Immunodeficiency Syndrome , Epidemics , HIV Infections , Humans , China/epidemiology , Male , Female , Middle Aged , Aged , HIV Infections/epidemiology , HIV Infections/transmission , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/transmission , Aged, 80 and over , Prevalence
4.
Expert Rev Clin Immunol ; : 1-14, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38690749

ABSTRACT

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal five-year survival rate of less than 10%. Neutrophils are key components of the innate immune system, playing a pivotal role in the PDAC immune microenvironment. AREAS COVERED: This review provides a comprehensive survey of the pivotal involvement of neutrophils in the tumorigenesis and progression of PDAC. Furthermore, it synthesizes preclinical and clinical explorations aimed at targeting neutrophils within the milieu of PDAC, subsequently proposing a conceptual framework to propel further inquiry focused on enhancing the therapeutic efficacy of PDAC through neutrophil-targeted strategies. PubMed and Web of Science databases were utilized for researching neutrophils in pancreatic cancer publications prior to 2024. EXPERT OPINION: Neutrophils play roles in promoting tumor growth and metastasis in PDAC and are associated with poor prognosis. However, the heterogeneity and plasticity of neutrophils and their complex relationships with other immune cells and extracellular matrix also provide new insights for immunotherapy targeting neutrophils to achieve a better prognosis for PDAC.

6.
Biomed Environ Sci ; 37(4): 341-353, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38727157

ABSTRACT

Objective: Hydroquinone (HQ), one of the phenolic metabolites of benzene, is widely recognized as an important participant in benzene-induced hematotoxicity. However, there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods: In this study, we treated K562 cells with 40 µmol/L HQ for 72 h, examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring (PRM), and performed bioinformatics analysis to identify interaction networks. Results: One hundred and eighty-seven upregulated differentially expressed proteins (DEPs) and 279 downregulated DEPs were identified in HQ-exposed K562 cells, which were involved in neutrophil-mediated immunity, blood microparticle, and other GO terms, as well as the lysosome, metabolic, cell cycle, and cellular senescence-related pathways. Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways, we constructed the network of protein interactions and determined 6 DEPs (STAT1, STAT3, CASP3, KIT, STAT5B, and VEGFA) as main hub proteins with the most interactions, among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion: Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.


Subject(s)
Benzene , Hemolytic Agents , Proteome , Proteome/metabolism , Proteomics , Benzene/toxicity , K562 Cells , Humans , Toxicity Tests/methods , Hemolytic Agents/toxicity
7.
Zhongguo Zhong Yao Za Zhi ; 49(4): 884-893, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621895

ABSTRACT

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Drugs, Chinese Herbal , Sepsis , Humans , Medicine, Chinese Traditional , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Sepsis/complications , Sepsis/drug therapy , Apoptosis , Signal Transduction , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology
8.
Front Pharmacol ; 15: 1282480, 2024.
Article in English | MEDLINE | ID: mdl-38666023

ABSTRACT

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model. Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline. Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem. Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection.

9.
Environ Sci Technol ; 58(18): 7838-7848, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38656157

ABSTRACT

Large volumes of water are used in energy production for both primary (e.g., fuel extraction) and secondary energy (e.g., electricity). In countries such as China, with a large internal trade in fuels and long-distance transmission grids, this can result in considerable water inequalities. Previous research focused on the water impacts of energy production at the national and provincial levels, which is too coarse to identify the spatial differences and make specific case studies. Here, we take the next step toward a spatially explicit economically integrated water-use for energy assessment by combining a bottom-up assessment approach with a city-level multiregional input-output model. Specifically, we examine the water consumption of energy production in China, distinguishing between water for primary and secondary energy at the level of coal mines, oil and gas fields, and power plants for the first time. Of the total energy-related freshwater consumption of 4.9 Gm3 in 2017, primary energy accounted for 19% (940 Mm3) and secondary energy accounted for 81% (3955 Mm3). Coal was the largest water consumer for both primary and secondary energy (540 and 3880 Mm3, respectively), with both oil (361, and 0.5 Mm3, respectively) and gas (7 and 69 Mm3, respectively) also consuming large amounts. Intercity virtual water, that is, water embodied in energy trade across cities, reached 54% (2.6 Gm3) of energy-related freshwater consumption. Across China, 32% of cities see a bilateral trade in secondary- and primary-energy-related virtual water (e.g., Daqing city exports virtual water embodied in primary fuel to other cities that is then used to produce electricity in those cities, part of which is used back in Daqing via transmission). For these 32% of cities, 73% export more virtual water than import and 27% import more virtual water than export. This study reveals significant differences in city-level virtual water patterns (e.g., scale and direction) between primary and secondary energy to provide information for cities about their virtual water inflow and outflow and the potential collaboration partners for water management.


Subject(s)
Cities , China , Power Plants , Water
10.
Sci Rep ; 14(1): 8892, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38632335

ABSTRACT

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions.


Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , Adult , Humans , Holidays , Taiwan , Time Factors , Risk Factors , Hospital Mortality , Patient Admission , Retrospective Studies
11.
Cardiovasc Endocrinol Metab ; 13(2): e0300, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38633361

ABSTRACT

Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.

12.
Front Pharmacol ; 15: 1337633, 2024.
Article in English | MEDLINE | ID: mdl-38650630

ABSTRACT

Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.

13.
FEBS J ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38652546

ABSTRACT

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils. Knockout of tdh causes a decrease in neutrophil number and slightly suppresses their acute injury-induced migration, but, unlike the mESCs, the level of H3K4me3 is not evidently reduced in neutrophils sorted from the kidney marrow of adult tdh-null zebrafish. These phenotypes are dependent on the enzymatic activity of Tdh. Importantly, a soluble supplement of nutrients that are able to fuel the acetyl-CoA pool, such as pyruvate, glucose and branched-chain amino acids, is sufficient to rescue the reduction in neutrophils caused by tdh deletion. In summary, our study presents evidence for the functional requirement of Tdh-mediated threonine metabolism in a developmental process in vivo. It also provides an animal model for investigating the nutritional regulation of myelopoiesis and immune response, as well as a useful tool for high-throughput drug/nutrition screening.

14.
Sci Rep ; 14(1): 9564, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671037

ABSTRACT

Clarifying the relationship between the man-machine environment and its impact on the tunnel wall drilling task performance (TWDTP) is crucial for enhancing the task performance. Based on a questionnaire survey, indicators of the man-machine environment that affect the TWDTP were proposed in this study, and exploratory factor analysis and a structural equation model were employed to examine the potential factors influencing the task performance and their degrees of influence. By comparing the discrepancy between the perceived performance and importance, the satisfaction of potential factors was evaluated, and the priority order for optimizing these factors was determined by considering the degree of influence and dissatisfaction. The results of survey data analysis based on actual tunnel drilling operation scenarios indicated that tools had the greatest impact on the TWDTP, followed by the quality of the physical environment, while human factors had the least influence on the task performance. Convenient functional maintenance is the key to improving the TWDTP, along with enhancing the quality of the working environment. Once these main aspects are optimized, it is important to consider additional factors such as availability of spare tools, efficient personnel organization, man-tool matching, and safety and health assurance. This research approach provides significant guidance in understanding the relationships between the man-machine environmental factors affecting the performance of complex engineering tasks and identifying key influencing factors, thus providing essential insights for optimizing the TWDTP.

15.
J Clin Med ; 13(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38673691

ABSTRACT

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

16.
Gut ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38621924

ABSTRACT

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

17.
Cardiovasc Diabetol ; 23(1): 138, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664801

ABSTRACT

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.


Subject(s)
Caveolin 1 , Diet, High-Fat , Endothelial Cells , Endothelium, Vascular , Mice, Inbred C57BL , Nitric Oxide Synthase Type III , Vasodilation , Animals , Male , Mice , Aorta/enzymology , Aorta/physiopathology , Aorta/metabolism , Aorta/drug effects , Aorta/pathology , Caveolin 1/metabolism , Caveolin 1/deficiency , Caveolin 1/genetics , Cells, Cultured , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/physiopathology , Endothelial Cells/enzymology , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Endothelium, Vascular/physiopathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/enzymology , Endothelium, Vascular/drug effects , Mice, Knockout , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Obesity/enzymology , Obesity/physiopathology , Obesity/metabolism , Signal Transduction , Sterol Esterase/metabolism , Sterol Esterase/genetics , Ubiquitination , Vasodilation/drug effects
18.
QJM ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38603614
19.
World J Gastroenterol ; 30(10): 1420-1430, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38596496

ABSTRACT

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.


Subject(s)
Choledochal Cyst , Humans , Female , Rats , Animals , Choledochal Cyst/surgery , Reproducibility of Results , Rats, Sprague-Dawley , Models, Animal , Dilatation, Pathologic , Bilirubin , Disease Models, Animal
20.
Ann Surg Treat Res ; 106(4): 225-230, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38586557

ABSTRACT

Purpose: Whether a dilated intrahepatic bile duct (IHBD) has any effect on the prognosis of choledochal cyst (CC) remains controversial. We aimed to summarize the clinical characteristics and prognosis of CC with IHBD dilatation. Methods: One hundred ninety-two children diagnosed with CC were identified, including 127 without IHBD dilatation (group A) and 65 with IHBD dilatation (group B). A retrospective analysis was performed to explore the clinical characteristics and prognosis of CC with IHBD dilatation based on clinical indices, symptoms, and complications. Results: Compared with group A, incidences of jaundice and fever were higher in group B (P = 0.010 and P = 0.033). Preoperative total bilirubin, direct bilirubin, and indirect bilirubin were increased in group B compared to group A (P = 0.005, P < 0.001, and P = 0.014), as were preoperative ALT, AST, γ-GT, and total bile acid (P = 0.006, P = 0.025, P < 0.001, and P = 0.024). The risk of liver fibrosis or cirrhosis was significantly increased for group B compared with group A (P = 0.012) and also occurred earlier in group B (P = 0.006). In the dilated IHBDs, 95.4% (62 of 65) recovered to normal, and more than half of dilated IHBDs (37 of 65) recovered to normal in 1 week. Conclusion: Most IHBDs can recover to normal postoperatively in a short time, and proactive treatment is recommended for CC patients with IHBD dilatation for significant abnormal liver functions.

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