Low-dose alcohol exacerbates hyperdynamic circulation and shunting in non-alcoholic cirrhotic rats.

BACKGROUND: Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. The present study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated. RESULTS: The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats; however, it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were up-regulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003). CONCLUSIONS: In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis.

Pulmonary Vascular Permeability and Extravascular Lung Water Index in Patients with Liver Cirrhosis and Septic Shock.

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

Compression and acceleration of ions by ultrashort, ultraintense azimuthally polarized light.

An efficient plasma compression scheme using azimuthally polarized light is proposed. Azimuthally polarized light possesses a donutlike intensity pattern, enabling it to compress and accelerate ions toward the optical axis across a wide range of parameters. When the light intensity reaches the relativistic regime of 10^{18}W/cm^{2}, and the plasma density is below the critical density, protons can be compressed and accelerated by the toroidal soliton formed by the light. The expansion process of the soliton can be well described by the snowplow model. Three-dimensional particle-in-cell simulations show that within the soliton regime, despite the ion density exceeding ten times the critical density, the ions' energy is insufficient for efficient neutron production. When the light intensity increases to 10^{22}W/cm^{2}, and the plasma density reaches several tens of times the critical density, deuterium ions can be compressed to thousands of times the critical density and simultaneously accelerated to the MeV level by tightly focused azimuthally polarized light during the hole-boring process. This process is far more dramatic compared to the soliton regime and can produce up to 10^{4} neutrons in a few light cycles. Moreover, in the subsequent beam-target stage, neutron yield is estimated to exceed 10^{8}. Finally, we present a comparison with the results obtained using a radially polarized light to examine the influence of light polarization.

Enhancing recombinant antibody yield in Chinese hamster ovary cells.

A range of recombinant monoclonal antibodies (rMAbs) have found application in treating diverse diseases, spanning various cancers and immune system disorders. Chinese hamster ovary (CHO) cells have emerged as the predominant choice for producing these rMAbs due to their robustness, ease of transfection, and capacity for posttranslational modifications akin to those in human cells. Transient transfection and/or stable expression could be conducted to express rMAbs in CHO cells. To bolster the yield of rMAbs in CHO cells, a multitude of approaches have been developed, encompassing vector optimization, medium formulation, cultivation parameters, and cell engineering. This review succinctly outlines these methodologies when also addressing challenges encountered in the production process, such as issues with aggregation and fucosylation.

Fructooligosaccharides reverses hepatic vascular dysfunction and dysbiosis in rats with liver cirrhosis and portal hypertension.

BACKGROUND: Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations. RESULTS: Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that Negativicutes, Selenomonadales and Lactobacillus salivarius reduced in the fructooligosaccharides-treated group. CONCLUSION: In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress.

Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes.

Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H2O2 exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.

Working Experiences of Care Aides in Long-Term Care Institutions Following the Relaxation of COVID-19 Regulations in Taiwan: A Qualitative Study.

Care aides in long-term care (LTC) institutions care for older disabled residents at high risk for COVID-19. However, they experienced many stressors during the COVID-19 pandemic. This study aims to explore the working experiences of care aides in LTC institutions following the relaxation of COVID-19 regulations in Taiwan. This qualitative descriptive study included 20 care aides who had cared for residents with COVID-19. Data were obtained via semi-structured interviews. Caring for residents with COVID-19 and the difficulties, resources and teamwork, and impact of care aides' work on their lives were discussed. Consequently, four themes were identified. First, difficulties in care, which included physical limitations by protection, workload, and impact of work schedule on the lives of the care aides. Second, psychological impact, such as worry, social isolation, and burnout. Third, interpersonal relationships with supervisors, colleagues, residents, and their families. Fourth, infection control policy from the institution and government. When infection control policies were relaxed, care aides had difficulties in caring for residents; furthermore, their family and social lives were also affected. They were required to learn knowledge of and skills for COVID-19 management. Institutions were required to provide support in materials, care processes, environment, and management.

Preparation of dearomatized p-coumaric acid derivatives as DNA damage response inhibitors with potent in vitro antitumor effect.

Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1-mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA-MB-231 than on MCF-7 cells. The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives.

Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes.

Outcomes with T-wave discordance of left bundle branch block and preserved or mildly reduced ejection fraction.

AIMS: Left bundle branch block (LBBB) is associated with an increased risk of adverse outcomes for patients with heart failure. The prognosis of LBBB in patients with a preserved ejection fraction (EF) remains controversial. This study investigated the predictive value of T-wave discordance for the prognosis of patients with LBBB and preserved or mildly reduced EF. METHODS AND RESULTS: We enrolled 707 patients with complete LBBB and left ventricular (LV) EF ≥ 40% observed using electrocardiograms (ECGs) and echocardiograms between January 2010 and December 2018. Their serial ECGs were reviewed during the follow-up period. The T-wave pattern was classified as discordant LBBB (dLBBB) or concordant LBBB (cLBBB) according to the 12-lead ECG T-wave morphology. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure during a median follow-up period of 3.1 years. A multivariable Cox regression analysis was used to evaluate the independent predictors of the primary outcome. Patients with dLBBB had more comorbidities, a higher heart rate, a longer QRS and QTc duration, a larger LV end-systolic volume and left atrial dimension, a lower LVEF, and a higher mitral E/A ratio and E/e', compared with those with cLBBB. Older age [hazard ratio (HR) = 1.023, 95% confidence interval (CI) = 1.001-1.046, P = 0.023], history of heart failure (HR = 2.440, 95% CI = 1.524-3.905, P = 0.001), chronic kidney disease (HR = 1.917, 95% CI = 1.182-3.110, P = 0.008), larger LV end-systolic volume (HR = 1.046, 95% CI = 1.017-1.075, P = 0.002), lower LVEF (HR = 0.916, 95% CI = 0.885-0.948, P = 0.001), and presence of dLBBB (HR = 1.63, 95% CI = 1.011-2.628, P = 0.032) were independent predictors of the primary outcome in patients with LBBB and LVEF ≥ 40%. The discordant or concordant T-wave morphology of LBBB could transform from one subtype to the other in up to 23% of the study population during the follow-up period, and individuals with persistent or transformed dLBBB faced an increased risk of cardiovascular death or non-fatal heart failure hospitalization. CONCLUSIONS: In patients with LBBB and EF ≥ 40%, dLBBB serves as an independent predictor of a higher risk of cardiovascular death or non-fatal heart failure hospitalization.

TRPV4 promotes HBV replication and capsid assembly via methylation modification of H3K4 and HBc ubiquitin.

Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.

Incidence, prevalence, and medical costs of pressure injuries in Taiwan from 2001 to 2015: Results of a retrospective cohort study.

AIMS AND OBJECTIVES: This study aims to analyse the trends in the incidence, prevalence and medical costs of pressure injuries (PIs) among genders in Taiwan. BACKGROUND: The treatment of PIs is complex and costly, often leading to complications and increased mortality. This issue significantly impacts healthcare quality and incurs substantial medical and social costs, warranting attention. METHODS: A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Database to obtain and calculate the incidence, prevalence, and medical costs of PIs in the country between 2001 and 2015 as well as to analyse high-risk groups and the medical care utilisation of patients following the STROBE reporting guidelines. RESULTS: Between 2001 and 2015, 15,327 incident case of PIs were diagnosed. During the study period, the prevalence rate of PIs per 100,000 population rose from 26.3 to 189.6, with approximately 11.5%-16.3% of patients undergoing surgical debridement. The PIs prevalence rate increased by 7.2-fold, and hospitalisation costs accounted for 91.7%-96.0% of the total medical costs. Patients with older age, comorbidities, poorer financial status and lower education levels were found to be likely to develop PIs. These predisposing factors differed between males and females. The prevalence of PIs was higher in patients ≥75 years old than in patients from other age groups. Moreover, PI-related medical expenses have been increasing annually. CONCLUSIONS: In Taiwan, the rising incidence of PIs is driving up medical costs. Effective care and prevention of PIs necessitate a comprehensive plan from the entire healthcare system. RELEVANCE TO CLINICAL PRACTICE: This research fills a gap in the available data on the incidence, prevalence, and medical costs of PIs in Taiwan and Asia. PATIENT OR PUBLIC CONTRIBUTION: The findings can be used to help develop clinical guidelines for preventive education and treatment of PIs.

Predicting impaired cardiopulmonary exercise capacity in patients with atrial fibrillation using a simple echocardiographic marker.

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy.

BACKGROUND: Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment, the feasibility and safety of this approach for laparoscopic pancreaticoduodenectomy (LPD) require further clinical evaluation and investigation. AIM: To explore the application value of the "five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD patients. METHODS: A total of 52 patients who underwent LPD via the "five steps four quadrants" modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed retrospectively. The patients' body mass index (BMI), preoperative laboratory indices, intraoperative variables and postoperative complications were recorded. The relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also analyzed. RESULTS: Among the 52 patients, 36 were males and 16 were females, and the average age was 62.2 ± 11.0 years. There were 26 patients with pancreatic head cancer, 16 patients with periampullary cancer, and 10 patients with distal bile duct cancer. The BMI was 22.3 ± 3.3 kg/m², and the median total bilirubin (TBIL) concentration was 57.7 (16.0-155.7) µmol/L. All patients successfully underwent the "five steps four quadrants" modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic leakage. Correlation analysis revealed significant associations between preoperative BMI (r = 0.3581, P = 0.0091), TBIL level (r = 0.2988, P = 0.0341), prothrombin time (r = 0.3018, P = 0.0297) and lymph node dissection time. Moreover, dissection time was significantly correlated with intraoperative blood loss (r = 0.7744, P < 0.0001). Further stratified analysis demonstrated that patients with a preoperative BMI ≥ 21.9 kg/m² and a TIBL concentration ≥ 57.7 µmol/L had significantly longer lymph node dissection times (both P < 0.05). CONCLUSION: The "five steps four quadrants" modularized en bloc dissection technique for accessing the hepatic hilum lymph node is safe and feasible for LPD. This technique is expected to improve the efficiency of hepatic hilum lymph node dissection and shorten the learning curve; thus, it is worthy of further clinical promotion and application.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

The Predictive Value of Gut Microbiota Composition for Sustained Immunogenicity following Two Doses of CoronaVac.

CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. Bacteroides uniformis (log10LDA score = 4.39) and Bacteroides eggerthii (log10LDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with B. eggerthii (OR: 5.73; 95% CI: 1.32-29.55; p = 0.022) and B. uniformis with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; p = 0.110). Additionally, B. uniformis was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (log10LDA score = 2.88) and II (log10LDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species (B. eggerthii and B. uniformis) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.

Ezetimibe treatment reduces oxidized low-density lipoprotein in biliary cirrhotic rats.

BACKGROUND: In liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats. METHODS: Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/d) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, and oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment. RESULTS: The BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia, and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry, or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL, and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like ox-LDL rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis. CONCLUSION: Ezetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats.

Caffeic acid ethanolamide induces antifibrosis, anti-inflammatory, and antioxidant effects protects against bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease; its cause is unknown, and it leads to notable health problems. Currently, only two drugs are recommended for IPF treatment. Although these drugs can mitigate lung function decline, neither can improve nor stabilize IPF or the symptoms perceived by patients. Therefore, the development of novel treatment options for pulmonary fibrosis is required. The present study investigated the effects of a novel compound, caffeic acid ethanolamide (CAEA), on human pulmonary fibroblasts and evaluated its potential to mitigate bleomycin-induced pulmonary fibrosis in mice. CAEA inhibited TGF-ß-induced α-SMA and collagen expression in human pulmonary fibroblasts, indicating that CAEA prevents fibroblasts from differentiating into myofibroblasts following TGF-ß exposure. In animal studies, CAEA treatment efficiently suppressed immune cell infiltration and the elevation of TNF-α and IL-6 in bronchoalveolar lavage fluid in mice with bleomycin-induced pulmonary fibrosis. Additionally, CAEA exerted antioxidant effects by recovering the enzymatic activities of oxidant scavengers. CAEA directly inhibited activation of TGF-ß receptors and protected against bleomycin-induced pulmonary fibrosis through inhibition of the TGF-ß/SMAD/CTGF signaling pathway. The protective effect of CAEA was comparable to that of pirfenidone, a clinically available drug. Our findings support the potential of CAEA as a viable method for preventing the progression of pulmonary fibrosis.

Effectiveness of a Digital Decision Aid for Nutrition Support in Women with Gynaecological Cancer: A Comparative Study.

This study aimed to examine the effects of an animated Patient Decision Aid (PtDA) about dietary choices on decisional conflict and decision regret. A prospective, observational, two-group comparative effectiveness study was conducted with patients (n = 90) from a southern Taiwan oncology inpatient unit. Data included the Malnutrition Universal Screening Tool (MUST), laboratory results, 16-item Decisional Conflict Scale (sf-DCS), and 5-item Decision Regret Scale (DRSc). Data were collected at admission (T0), after the first-cycle of chemotherapy but before discharge (T1), and after the six-cycle chemotherapy protocol (T2) (around 3 months). Group A received standardized nutrition education and a printed brochure, while Group B watched a 10-minute information video during a one-on-one inpatient consultation and engaged in a values clarification exercise between T0 and T1. The percentage of women with a MUST score ≧1 in Group A sharply increased over time, but not in Group B. Decision aid usage significantly increased patients' hemoglobin and lymphocyte values over time (p < 0.05). The digital PtDA contributed to less decisional conflict and decision regret in at-risk patients and improved their nutritional well-being. Decision-aids help patients make healthcare decisions in line with their values, and are sustainable for use by busy clinicians.