The intestinal microbiota is closely associated with the development of obesity and nonalcoholic fatty liver disease (NAFLD). This study investigated the effects of probiotic treatment on visceral ...fat area (VFA) and intrahepatic fat (IHF) fraction in NAFLD. Sixty-eight obese NAFLD patients (>5% proton density fat fraction PDFF on magnetic resonance imaging MRI) were randomized to probiotic and placebo groups for 12 weeks. The probiotic mixture included 6 bacterial species. VFA and IHF were measured using the MRI-PDFF technique. Body weight and total body fat were reduced in the probiotic group but not in the placebo group. The mean IHF fraction was reduced after 12 weeks of treatment in the probiotic group compared to that at baseline (from 16.3 ± 15.0% to 14.1 ± 7.7%, p = 0.032) but was not reduced in the placebo group. The decrease in IHF (mean difference: -2.61%, p = 0.012) was also greater in the probiotic group than in the placebo group. Reduction of triglyceride was greater in the probiotic treatment group than in the placebo group (mean difference: -34.0 mg/dl, p = 0.0033). However, the changes in IHF percentage and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight. Treatment with probiotics for 12 weeks resulted in significant reduction in IHF and body weight in obese NAFLD patients.
Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it ...displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.
Background & Aims
Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is ...necessary to investigate the safety and efficacy of Ate/Bev in real settings.
Methods
This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first‐line treatment for advanced HCC from 11 institutions. We excluded patients with Child‐Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis.
Results
According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow‐up duration was 5.9 months (95% confidence interval CI, 5.4‐6.4), the median progression‐free survival (PFS) was 6.5 months (95% CI, 4.1‐9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3‐4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil‐to‐lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P < .001) were significantly associated with worse OS.
Conclusions
Ate/Bev showed real‐life efficacy and safety in Korean patients with advanced HCC, in line with results from phase III trial. Considering unfavourable survival outcomes of Ate/Bev in patients with elevated NLR, careful assessment of treatment response needs to be performed in this group.
The diagnostic yield of endomyocardial biopsy in cardiac sarcoidosis (CS) is quite low because of the patchy involvement, and for the diagnosis of CS, existing guidelines required histological ...confirmation. Therefore, especially for isolated CS, diagnosis consistent with the guidelines cannot be made in a large number of patients. With recent developments in imaging modalities such as cardiac magnetic resonance and 18-fluorodeoxyglucose positron emission tomography, diagnosing CS has become easier and diagnostic criteria for CS not compulsorily requiring histological confirmation have been suggested. Despite significant advances in diagnostic tools, large-scale studies that can guide treatment plans are still lacking, and treatment has relied on the experience accumulated over the past years and the consensus of experts. However, opinions vary, depending on the situation, which is quite puzzling for the physician treating CS. Moreover, with the advent of new immunosuppressant agents, these new drugs have been applied under the assumption that the effect of immunosuppression is not much different from that of other well-known autoimmune diseases that require immunosuppression. However, we should wait to see the beneficial effects of these new immunosuppressants before we attempt to apply these agents in our clinical practice. This review summarises the widely used diagnostic criteria, current diagnostic modalities and recommended treatments for sarcoidosis. We have added our opinions on selecting or modifying diagnostic and treatment plans from the diverse current recommendations.
Background
There is a close link between
Fusobacterium nucleatum
and colorectal cancer (CRC) tumorigenesis and chemoresistance. However, the genetic characteristics and clinical significance of CRC ...related with
F. nucleatum
remains unclear. This study evaluated the relationship between
F. nucleatum
, pathway mutation, and patient prognosis.
Methods
Fusobacterium nucleatum
amount in the tumor tissue and adjacent normal tissue were measured by quantitative polymerase chain reaction in adjuvant (
N
= 128) and metastatic (
N
= 118) cohorts. Patients were divided into binary (
F. nucleatum
-high and
F. nucleatum
-low) according to
F. nucleatum
amount. Targeted next-generation sequencing of 40 genes included in the 5 critical pathways (WNT, P53, RTK-RAS, PI3 K, and TGF-β) was performed in the adjuvant cohort.
Results
Patients with MSI-H and CIMP-H had higher amount of
F. nucleatum
in tumor tissue.
Fusobacterium nucleatum
-high patients had higher rates of transition mutation and C to T (G to A) nucleotide change regardless of MSI status. In addition, mutation rate of
AMER1
and
ATM
genes, and TGF-β pathway was higher in
F. nucleatum
-high patients.
Fusobacterium nucleatum
-high was associated with poor overall survival (OS) in the palliative cohort (26.4 vs. 30.7 months,
p
= 0.042). Multivariate analysis revealed
F. nucleatum
-high as an independent negative prognostic factor for OS adjusted hazard ratio of 1.69 (95% confidence interval 1.04–2.75),
p
= 0.034. However,
F. nucleatum
amount was not associated with recurrence in the adjuvant cohort.
Conclusions
F. nucleatum
-high was associated with poor survival in metastatic CRC. In addition, we identified mutational characteristics of colorectal cancer according to
F. nucleatum
amount.
Although statins are an effective strategy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population, the benefits for dialysis patients are ...controversial. We sought to assess trends of statin use and evaluate outcomes of statin therapy in dialysis patients with different types of ASCVD.
This nationwide retrospective population-based cohort study using data from the Korean National Health Insurance Service included adult patients (aged ≥ 18 years) undergoing chronic dialysis who had an initial ASCVD event in the time period of 2013 to 2018. Annual trends of statin use according to age, sex, and ASCVD types were analyzed. The association between 1-year mortality and statin use was examined using multivariable Cox proportional hazards regression analyses.
Among 17,242 subjects, 9,611(55.7%) patients were statin users. The overall prevalence of statin use increased from 52.9% in 2013 to 57.7% in 2018; the majority (77%) of dialysis patients were prescribed moderate-intensity statins. The proportions of low- or moderate-intensity statin use were similar, but high-intensity statin use increased from 5.7% in 2013 to 10.5% in 2018. The use of the statin/ezetimibe combination has gradually increased since 2016. Statin use was independently associated with the reduced 1-year all-cause mortality after adjusting for confounding factors (hazard ratio HR 0.89, 95% confidence interval CI 0.80-0.96, P = 0.004).
The prevalence of statin prescriptions in dialysis patients after ASCVD event increased from 2013 to 2018. Most patients received moderate-intensity statin. However, high-intensity statin and statin/ezetimibe combination therapy has remarkably increased. Statin use was associated with decreased 1-year all-cause mortality in dialysis patients with ASCVD.
In the United States, non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and associated with higher mortality according to data from earlier National Health and Nutrition ...Examination Survey (NHANES) 1988-1994. Our goal was to determine the NAFLD prevalence in the recent 1999-2012 NHANES, risk factors for advanced fibrosis (stage 3-4) and mortality. NAFLD was defined as having a United States Fatty Liver Index (USFLI) > 30 in the absence of heavy alcohol use and other known liver diseases. The probability of low/high risk of having advanced fibrosis was determined by the NAFLD Fibrosis Score (NFS). In total, 6000 persons were included; of which, 30.0% had NAFLD and 10.3% of these had advanced fibrosis. Five and eight-year overall mortality in NAFLD subjects with advanced fibrosis was significantly higher than subjects without NAFLD ((18% and 35% vs. 2.6% and 5.5%, respectively) but not NAFLD subjects without advanced fibrosis (1.1% and 2.8%, respectively). NAFLD with advanced fibrosis (but not those without) is an independent predictor for mortality on multivariate analysis (HR = 3.13, 95% CI 1.93-5.08, p<0.001). In conclusion, in this most recent NHANES, NAFLD prevalence remains at 30% with 10.3% of these having advanced fibrosis. NAFLD per se was not a risk factor for increased mortality, but NAFLD with advanced fibrosis was. Mexican American ethnicity was a significant risk factor for NAFLD but not for advanced fibrosis or increased mortality.
Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant ...activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.
•Isolation of rutin from Dendropanax morbifera Leveille with anti-thrombotic activity.•Rutin was found to inhibit fibrin clotting and thrombin activity effectively.•Rutin inhibited thrombosis and acute thromboembolism.•Rutin exhibited anticoagulant and anti-platelet properties.
Nakai root contains decursin which exerts beneficial properties such as anti-amnesic and anti-inflammatory activities. Until now, however, the neuroprotective effects of decursin against transient ...ischemic injury in the forebrain have been insufficiently investigated. Here, we revealed that post-treatment with decursin and the root extract saved pyramidal neurons in the hippocampus following transient ischemia for 5 min in gerbil forebrain. Through high-performance liquid chromatography, we defined that decursin was contained in the extract as 7.3 ± 0.2%. Based on this, we post-treated with 350 mg/kg of extract, which is the corresponding dosage of 25 mg/kg of decursin that exerted neuroprotection in gerbil hippocampus against the ischemia. In addition, behavioral tests were conducted to evaluate ischemia-induced dysfunctions via tests of spatial memory (by the 8-arm radial maze test) and learning memory (by the passive avoidance test), and post-treatment with the extract and decursin attenuated ischemia-induced memory impairments. Furthermore, we carried out histochemistry, immunohistochemistry, and double immunohistofluorescence. Pyramidal neurons located in the subfield cornu ammonis 1 (CA1) among the hippocampal subfields were dead at 5 days after the ischemia; however, treatment with the extract and decursin saved the pyramidal neurons after ischemia. Immunoglobulin G (IgG, an indicator of extravasation), which is not found in the parenchyma in normal brain tissue, was apparently shown in CA1 parenchyma from 2 days after the ischemia, but IgG leakage was dramatically attenuated in the CA1 parenchyma treated with the extract and decursin. Furthermore, astrocyte endfeet, which are a component of the blood-brain barrier (BBB), were severely damaged at 5 days after the ischemia; however, post-treatment with the extract and decursin dramatically attenuated the damage of the endfeet. In brief, therapeutic treatment of the extract of
Nakai root and decursin after 5 min transient forebrain ischemia protected hippocampal neurons from the ischemia, showing that ischemia-induced BBB leakage and damage of astrocyte endfeet was significantly attenuated by the extract and decursin. Based on these findings, we suggest that
Nakai root containing decursin can be employed as a pharmaceutical composition to develop a therapeutic strategy for brain ischemic injury.
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