Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Characterization of the intestinal transport mechanism of polystyrene microplastics (MPs) and the potential inhibitory effect of green tea extracts on MPs intestinal absorption.

The aims of the current study included characterizing the intestinal transport mechanism of polystyrene microplastics (MPs) with different charges and sizes in the intestinal epithelial cell model and determining the inhibitory effect of green tea extracts (GTEs) on the intestinal absorption of MPs in Caco-2 cells. The smaller sizes, which included diameters of 0.2 µm, of amine-modified MPs compared to either larger size (1 µm diameter, or carboxylate-MPs (0.2 and 1 µm diameter) significantly lowered the cell viability of caco-2 cells that were measured by MTT assay (p < 0.05). The transported amount (particles/mL of the cell media) of amine-modified MPs by the Caco-2 cell, was not dependent according to the concentrations, energy, or temperature, but it was higher than the carboxylate-modified MPs. The co-treatment of GTEs with the amine-modified MPs inhibited Caco-2 cell cytotoxicity as well as reduced the production of intracellular reactive oxygen species (ROS) in HepG2 generated by the exposure of amine-modified MPs. The GTEs co-treatment also increased trans-epithelial electrical resistances (TEER) and reduced the transportation of Lucifer Yellow via the Caco-2 monolayer compared to only the amine-modified MPs exposure. The GTEs treatment led to a decrease in the number of amine-modified MPs transported to the basal side of the Caco-2 monolayer. The results from our study suggest that the consumption of GTEs could enhance the intestinal barrier function by recovering intestinal epithelial cell damage induced by MPs, which resulted in a decrease of the intestinal absorption of MPs.

Self-adjuvanted L-arginine-modified dextran-based nanogels for sustained local antigenic protein delivery to antigen-presenting cells and enhanced cellular and humoral immune responses.

In the development of cancer vaccines, antigens are delivered to elicit potent and specific T-cell responses to eradicate tumour cells. Nonetheless, successful vaccines are often hampered by the poor immunogenicity of tumour antigens, rapid clearance by the innate immunity, and limited cross-presentation on MHC-I to activate CD8+ T-cells arm. To address these issues, we developed dextran-based nanogels to promote antigen uptake, storage, and cross-presentation on MHC-I, while directing immunogenic maturation of the antigen-presenting cells (APCs). To promote the nanocarriers interaction with cells, we modified DX with L-arginine (Arg), whose immunomodulatory activities have been well documented. The ArgDX nanogel performance was compared with the nanogel modified with L-histidine (His) and L-glutamate (Glut). Moreover, we introduced pH-sensitive hydrazone crosslinking during the nanogel formation for the conjugation and controlled release of antigen ovalbumin (OVA). The OVA-laden nanogels have an average size of 325 nm. We demonstrated that the nanogels could rapidly release cargoes upon a pH change from 7 to 5 within 8 days, indicating the controlled release of antigens in the acidic cellular compartments upon internalization. Our results revealed that the ArgDX nanogel could promote greater antigen uptake and storage in DCs in vitro and promoted a stronger immunogenic maturation of DCs and M1 polarization of the macrophages. The OVA signals were co-localized with lysosomal compartments up till 96 hours post-treatment and washing, suggesting the nanogels could facilitate prolonged antigen storage and supply from endo-lysosomal compartments. Furthermore, all the tested nanogel formulations retained antigens at the skin injection sites until day 21. Such delayed clearance could be due to the formation of micron-sized aggregates of OVA-laden nanogels, extending the interactions with the resident DCs. Amongst the amino acid modifications, ArgDX nanogels promoted the highest level of lymph node homing signal CCR7 on DCs. The nanogels also showed higher antigen presentation on both MHC-I and II than DX in vitro. In the in vivo immune studies, ArgDX nanogels were more superior in inducing cellular and humoral immunity than the other treatment groups on day 21 post-treatment. These results suggested that ArgDX nanogel is a promising self-adjuvanted nanocarrier for vaccine delivery.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

Bidirectional Interactions between Green Tea (GT) Polyphenols and Human Gut Bacteria.

Green tea (GT) polyphenols undergo extensive metabolism within gastrointestinal tract (GIT), where their derivatives compounds potentially modulate the gut microbiome. This biotransformation process involves a cascade of exclusive gut microbial enzymes which chemically modify the GT polyphenols influencing both their bioactivity and bioavailability in host. Herein, we examined the in vitro interactions between 37 different human gut microbiota and the GT polyphenols. UHPLC-LTQ-Orbitrap-MS/MS analysis of the culture broth extracts unravel that genera Adlercreutzia, Eggerthella and Lactiplantibacillus plantarum KACC11451 promoted C-ring opening reaction in GT catechins. In addition, L. plantarum also hydrolyzed catechin galloyl esters to produce gallic acid and pyrogallol, and also converted flavonoid glycosides to their aglycone derivatives. Biotransformation of GT polyphenols into derivative compounds enhanced their antioxidant bioactivities in culture broth extracts. Considering the effects of GT polyphenols on specific growth rates of gut bacteria, we noted that GT polyphenols and their derivate compounds inhibited most species in phylum Actinobacteria, Bacteroides, and Firmicutes except genus Lactobacillus. The present study delineates the likely mechanisms involved in the metabolism and bioavailability of GT polyphenols upon exposure to gut microbiota. Further, widening this workflow to understand the metabolism of various other dietary polyphenols can unravel their biotransformation mechanisms and associated functions in human GIT.

1,5-Dicaffeoylquinic acid from Pseudognaphalium affine ameliorates dry eye disease via suppression of inflammation and protection of the ocular surface.

PURPOSE: Pseudognaphalium affine (P. affine), a medicinal plant, has long been used to treat various diseases due to its astringent and vulnerary effects. These therapeutic benefits are largely attributed to high contents of phytochemicals, such as flavonoids and polyphenols, that have anti-inflammatory and tissue-protective activities. Herein, we investigated the potential of dicaffeoylquinic acids (diCQAs), polyphenols from P. affine, as a novel treatment for dry eye disease (DED). METHODS: We isolated 1,5-, 3,4-, 3,5- and 4,5-diCQAs from the P. affine methanol extract, and tested the effects of diCQA isomers in cultures of human corneal epithelial cells (CECs) under desiccating hyperosmolar stress and in two mouse models for DED: desiccating environmental stress-induced DED and the NOD.B10-H2b mouse model of ocular Sjögren's syndrome. RESULTS: Initial screening showed that, among the diCQAs, 1,5-diCQA significantly inhibited apoptosis and enhanced viability in cultures of CECs under hyperosmolar stress. Moreover, 1,5-diCQA protected CECs by promoting proliferation and downregulating inflammatory activation. Subsequent studies with two mouse models of DED revealed that topical 1,5-diCQA administration dose-dependently decreased corneal epithelial defects and increased tear production while repressing inflammatory cytokines and T cell infiltration on the ocular surface and in the lacrimal gland. 1,5-diCQA was more effective in alleviating DED, as compared with two commercially-available dry eye treatments, 0.05% cyclosporine and 0.1% sodium hyaluronate eye drops. CONCLUSIONS: Together, our results demonstrate that 1,5-diCQA isolated from P. affine ameliorates DED through protection of corneal epithelial cells and suppression of inflammation, thus suggesting a novel DED therapeutic strategy based on natural compounds.

Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion.

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs.

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE).

Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) "selectively targetable" and "accessible to supraselective catheterization." The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5-2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the "drop test." Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

Summary of key guidelines for locoregional treatment of HCC in Asia, Europe, South and North America.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.

Silymarin Prevents High-Fat Diet-Induced Muscle Atrophy by Regulating Protein Degradation and Synthesis in Mice.

Silymarin is found in Silybum marianum. We investigated the effect of silymarin on muscle atrophy in obese mice. The experimental mice were divided into three groups: CON, normal diet; HFD, 60% high-fat diet (HF); and SILY: 50 mg silymarin +60% HF. It was confirmed that increases in body weight and fat mass in the SILY group were significantly inhibited. Moreover, the muscle mass in SILY mice was significantly higher than that in the HFD group. The grip strength in HFD group was significantly reduced, whereas in the SILY group it was higher than that in HFD group. In HFD mice, the mRNA levels of protein degradation factors (muscle ring-finger protein 1 [MuRF-1] and Atrogin-1) were increased and protein synthesis factors (phosphoinositide 3-kinase [PI3K] and Akt) were decreased. However, silymarin was found to elevate the degradation factors as compared with HFD group, whereas it reduced the synthesis factors. The results suggest that silymarin could prevent not only obesity but also muscle atrophy.

Iron overload and impaired iron handling contribute to the dystrophic pathology in models of Duchenne muscular dystrophy.

BACKGROUND: Oxidative stress is implicated in the pathophysiology of Duchenne muscular dystrophy (DMD, caused by mutations in the dystrophin gene), which is the most common and severe of the muscular dystrophies. To our knowledge, the distribution of iron, an important modulator of oxidative stress, has not been assessed in DMD. We tested the hypotheses that iron accumulation occurs in mouse models of DMD and that modulation of iron through the diet or chelation could modify disease severity. METHODS: We assessed iron distribution and total elemental iron using LA-ICP-MS on skeletal muscle cross-sections of 8-week-old Bl10 control mice and dystrophic mdx mice (with moderate dystrophy) and dystrophin/utrophin-null mice (dko, with severe dystrophy). In addition, mdx mice (4 weeks) were treated with either an iron chelator (deferiprone 150 mg/kg/day) or iron-enriched feed (containing 1% added iron as carbonyl iron). Immunoblotting was used to determine the abundance of iron- and mitochondria-related proteins. (Immuno)histochemical and mRNA assessments of fibrosis and inflammation were also performed. RESULTS: We observed a significant increase in total elemental iron in hindlimb muscles of dko mice (+50%, P < 0.05) and in the diaphragm of mdx mice (+80%, P < 0.05), with both tissues exhibiting severe pathology. Iron dyshomeostasis was further evidenced by an increase in the storage protein ferritin (dko: +39%, P < 0.05) and ferroportin compared with Bl10 control mice (mdx: +152% and dko: +175%, P < 0.05). Despite having features of iron overload, dystrophic muscles had lower protein expression of ALAS-1, the rate-limiting enzyme for haem synthesis (dko -44%, P < 0.05), and the haem-containing protein myoglobin (dko -54%, P < 0.05). Deferiprone treatment tended to decrease muscle iron levels in mdx mice (-30%, P < 0.1), which was associated with lower oxidative stress and fibrosis, but suppressed haem-containing proteins and mitochondrial content. Increasing iron via dietary intervention elevated total muscle iron (+25%, P < 0.05) but did not aggravate the pathology. CONCLUSIONS: Muscles from dystrophic mice have increased iron levels and dysregulated iron-related proteins that are associated with dystrophic pathology. Muscle iron levels were manipulated by iron chelation and iron enriched feed. Iron chelation reduced fibrosis and reactive oxygen species (ROS) but also suppressed haem-containing proteins and mitochondrial activity. Conversely, iron supplementation increased ferritin and haem-containing proteins but did not alter ROS, fibrosis, or mitochondrial activity. Further studies are required to investigate the contribution of impaired ferritin breakdown in the dysregulation of iron homeostasis in DMD.

Impact of flavonol extracts derived from green tea or targeted flavonols as secondary ingredients on intestinal glucose transport.

The purpose of the current study was to examine the effect of adding secondary ingredients such as green tea derived water-soluble polysaccharides (GTP) and flavonol aglycone rich fractions derived from cellulase treated green tea extract (FVN) into catechin rich green tea extracts (GTE) on wheat starch digestion and intestinal glucose transport using in vitro digestion with Caco-2 cells. Co-digestion of wheat starch with GTE (16.88 g L-1) or GTE + GTP + FVN (16.69 g L-1) appeared to promote starch hydrolysis compared to control (15.49 g L-1). In case of major flavonoids, addition of epigallocatechin gallate (EGCG), EGCG + myricetin (M) into wheat starch significantly increased the digestion of starch into glucose. Glucose transport rate decreased by 22.35% in wheat starch + GTE + GTP + FVN (1.39%), while the least amount of glucose (1.70%) was transported in EGCG mixed with M (1% of EGCG) as secondary ingredients among individual flavonoids formulation. It indicated that inhibitory effect on glucose transport was higher in addition of GTE, GTP, and FVN as excipients ingredients rather than targeted major flavonoids. Results from the current study suggest that whole green tea including flavonoid rich fractions could enhance hypoglycemic potential of GTE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05140-2.

Effect of Characterized Green Tea Extraction Methods and Formulations on Enzymatic Starch Hydrolysis and Intestinal Glucose Transport.

The purpose of the current study was to investigate the effect of various characterized green tea extracts (GTEs) according to extraction methods on enzymatic starch hydrolysis and intestinal glucose transport. Codigestion of wheat starch with water extract (WGT) or ethanol extract formulated with green tea polysaccharides and flavonols (CATEPLUS) produced 3.4-3.5 times higher resistant starch (RS) than wheat starch only. Its microstructures were changed to spherical shapes and smooth surfaces as shown by scanning electron microscopy (SEM) results. According to Fourier transform infrared (FT-IR) spectra, the absorption peak of O-H stretching was red-shifted in WGT or CATEPLUS. The results confirmed that hydrogen bonds were formed between starch granules and polysaccharides in WGT or CATEPLUS. Intestinal glucose transport subsequently measured after in vitro digestion was mostly suppressed in CATEPLUS. Gene expression of the glucose transporter protein, particularly SGLT1, was significantly inhibited by addition of CATEPLUS (p < 0.05). Results from the current study suggest that co-intake of green tea extracts formulated with green tea polysaccharides and flavonols could be a potentially useful means to delay blood glucose absorption when consuming starchy foods.

Characterized Polysaccharides from Green Tea Inhibited Starch Hydrolysis and Glucose Intestinal Uptake by Inducing Microstructural Changes of Wheat Starch.

The purpose of the current study was to investigate the effect of green tea ethanol extract (GTE) and polysaccharide fractions from green tea (PFGs) on the hydrolysis of wheat starch, microstructural changes, and intestinal transport of glucose. The amount of resistant starch (RS) was significantly lowered in the water-soluble polysaccharide (WSP), water-soluble polysaccharide-pectinase (WSP-P), and water-insoluble polysaccharide-alkali soluble (WISP-Alk-Soluble; p < 0.05). The microstructures of gelatinized wheat starch granules with WSP, WSP-P, and WISP-Alk-Soluble were spherical with small cracks. The amount of intestinal transported glucose from digested wheat starch was 2.12-3.50 times lower than the control group. The results from the current study suggest that water- and alkali-soluble PFGs could be potential ingredients to lower starch hydrolysis as well as to control the postprandial blood glucose level when foods that contain starch are consumed.

Ablation of persistent atrial fibrillation based on high density voltage mapping and complex fractionated atrial electrograms: A randomized controlled trial.

INTRODUCTION: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. However, a PVI alone has been considered insufficient for persistent AF. This study aimed to evaluate the efficacy of persistent AF ablation targeting complex fractionated atrial electrogram (CFAE) areas within low voltage zones identified by high-resolution mapping in addition to the PVI. METHODS: We randomized 50 patients (mean age 58.4 ±â€Š9.5 years old, 86.0% males) with persistent AF to a PVI + CFAE group and PVI only group in a 1:1 ratio. CFAE and voltage mapping was performed simultaneously using a Pentaray Catheter with the CARTO3 CONFIDENSE module (Biosense Webster, CA, USA). The PVI + CFAE group, in addition to the PVI, underwent ablation targeting low voltage areas (<0.5 mV during AF) containing CFAEs. RESULTS: The mean persistent AF duration was 24.0 ±â€Š23.1 months and mean left atrial dimension 4.9 ±â€Š0.5 cm. In the PVI + CFAE group, AF converted to atrial tachycardia (AT) or sinus rhythm in 15 patients (60%) during the procedure. The PVI + CFAE group had a higher 1-year AF free survival (84.0% PVI + CFAE vs 44.0 PVI only, P = .006) without antiarrhythmic drugs. However, there was no difference in the AF/AT free survival (60.0% PVI + CFAE vs 40.0% PVI only, P = .329). CONCLUSION: Persistent AF ablation targeting CFAE areas within low voltage zones using high-density voltage mapping had a higher AF free survival than a PVI only. Although recurrence with AT was frequent in the PVI+CFAE group, the sinus rhythm maintenance rate after redo procedures was 76%.

Simultaneous Pretreatment of Aspirin and Omega-3 Fatty Acid Attenuates Nuclear Factor-κB Activation in a Murine Model with Ventilator-Induced Lung Injury.

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

Profiling of In Vitro Bioaccessibility and Intestinal Uptake of Flavonoids after Consumption of Commonly Available Green Tea Types.

The aim of this study was to profile the bioaccessibility and intestinal absorption of epicatechins and flavonols in different forms of green tea and its formulation: loose leaf tea, powdered tea, 35% catechins containing GTE, and GTE formulated with green tea-derived polysaccharide and flavonols (CATEPLUS™). The bioaccessibillity and intestinal absorption of epicatechins and flavonols was investigated by using an in vitro digestion model system with Caco-2 cells. The bioaccessibility of total epicatechins in loose leaf tea, powdered tea, GTE, and CATEPLUS™ was 1.27%, 2.30%, 22.05%, and 18.72%, respectively, showing that GTE and CATEPLUS™ had significantly higher bioaccessibility than powdered tea and loose leaf tea. None of the flavonols were detected in powdered tea and loose leaf tea, but the bioaccessibility of the total flavonols in GTE and CATEPLUS™ was 85.74% and 66.98%, respectively. The highest intestinal absorption of epicatechins was found in CATEPLUS™ (171.39 ± 5.39 ng/mg protein) followed by GTE (57.38 ± 9.31), powdered tea (3.60 ± 0.67), and loose leaf tea (2.94 ± 1.03). The results from the study suggest that formulating green tea extracts rich in catechins with second components obtained from green tea processing could enhance the bioavailability of epicatechins.

Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.

Glue Embolization of Lymphopseudoaneurysm for Chylous Ascites after Retroperitoneal Surgery.

OBJECTIVE: To assess the safety and efficacy of lymphopseudoaneurysm (LPA) glue (n-butyl cyanoacrylate [NBCA]) embolization in the management of chylous ascites after retroperitoneal surgery. MATERIALS AND METHODS: A retrospective analysis from January 2014 to October 2018 was performed in six patients (4 females and 2 males; mean age, 45.3 ± 14.2 years; range, 26-61 years) who underwent LPA embolization for chylous ascites developing after retroperitoneal surgery involving the perirenal space (four donor nephrectomies, one partial nephrectomy, and one retroperitoneal lymphadenectomy). After placing a percutaneous drainage catheter into the LPA or adjacent lymphocele, embolization was performed by filling the LPA itself with a mixture of glue and Lipiodol (Guerbet). RESULTS: Daily drainage from percutaneously placed drains exceeded 300 mL/day despite medical and surgical treatment (volume: mean, 1173 ± 1098 mL; range, 305-2800 mL). Intranodal lymphangiography was performed in four of the six patients and revealed leakage in 2 patients. Percutaneous embolization of the LPA was successful in all patients using an NBCA and Lipiodol mixture in a ratio of 1:1-1:2 (volume: mean, 4.3 ± 1.1 mL; range, 3-6 mL). Chylous ascites was resolved and the drainage catheter was removed in all patients within 4 days after the procedure (mean, 2.0 ± 1.8 days; range, 0-4 days). No procedure-related complications or recurrence of chylous ascites occurred during a mean follow-up period of 37.3 months (range, 21.1-48.4 months). CONCLUSION: Glue embolization of LPA has the potential to be a feasible and effective treatment method for the management of chylous ascites after retroperitoneal surgery.

Spectral CT-Based Iodized Oil Quantification to Predict Tumor Response Following Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To quantify iodized oil retention in tumors after transarterial chemoembolization using spectral computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC) and evaluate its performance in predicting 12-month tumor responses. MATERIALS AND METHODS: From September 2017 to December 2018, 111 patients with HCC underwent initial conventional transarterial chemoembolization. Immediately after the procedure, unenhanced CT was performed using a spectral CT scanner, and the iodized oil densities in index tumors were measured. In tumor-level analyses, a threshold level of iodized oil density in the tumors was calculated using clustered receiver operating characteristic curve analyses to predict the 12-month tumor responses. In patient-level analyses, significant factors associated with a 12-month complete response, including the presence of tumors below the threshold value (ie, suspected residual tumors), were evaluated by logistic regression. RESULTS: Forty-eight HCCs in 39 patients were included in the analyses. The lower 10th percentile of the iodine density was identified as the threshold for determining the 12-month nonviable responses. The area under the curve of the iodine density measurements in predicting the 12-month nonviable responses was 0.893 (95% confidence interval, 0.797-0.989). The threshold value of the iodine density of 10.68 mg/mL yielded a sensitivity of 82.76% and specificity of 94.74% (P < .001). In the patient-level analysis, the 12-month complete response was significantly associated with the presence of a suspected residual tumor, with an odds ratio of 72.0 (95% confidence interval, 7.273-712.770). CONCLUSIONS: Spectral CT imaging using quantitative analysis of the iodized oil retention in target HCCs can predict tumor responses after a conventional transarterial chemoembolization procedure.