Feasibility of intraoperative pathologic examination for sentinel lymph nodes during sentinel node navigation surgery in early gastric cancer: results of pathologic protocol for SENORITA trial.

BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.

Association between dietary carotenoid intake and breast cancer risk: a case-control study among Korean women.

The association between dietary carotenoids and breast cancer (BC) risks were inconsistent. Therefore, this study investigated the association between dietary carotenoid and BC risks among Korean women. We recruited participants from the National Cancer Centre of Korea. Odds ratios and 95% confidence intervals were calculated with a logistic regression model. There was an inverse association between dietary carotenoid subclasses and BC risks; in particular, a higher intake of ß-carotene and lutein/zeaxanthin was associated with reduced BC risks. After subgroup analysis with estrogen receptor (ER)/progesterone receptor (PR) status, there was similar trend among ER-/PR- women. We further investigated which foods contribute to the carotenoid intake. A higher intake of radish leaves, kale, and bracken was associated with lowered BC risks. Accordingly, dietary carotenoid, particularly ß-carotene and lutein/zeaxanthin, appears to be associated with a lower risk of BC among Korean women.

Standard follow-up after curative surgery for advanced gastric cancer: secondary analysis of a multicentre randomized clinical trial (KLASS-02).

BACKGROUND: The benefit of regular follow-up after curative resection for gastric cancer is controversial as there is no evidence that it will improve survival. This study assessed whether regular follow-up leads to improved survival in patients after surgery for gastric cancer. METHODS: A secondary analysis was undertaken of patients who participated in an RCT of laparoscopic versus open distal gastrectomy for advanced gastric cancer between November 2011 and April 2015. Depending on whether patients were compliant with the initial trial follow-up protocol or not, they were analysed as having had either regular or irregular follow-up. Clinicopathological characteristics, recurrence patterns, detection, treatments, and survival were compared between the groups. RESULTS: The regular and irregular follow-up groups comprised 712 and 263 patients respectively. Disease recurrence within 36 months was more common in the regular group than in the irregular group (17.0 versus 11.4 per cent; P = 0.041). Recurrence patterns did not differ between the groups. The 3-year recurrence-free survival rate was worse in the regular than in the irregular group (81.2 versus 86.5 per cent; P = 0.031). However, the 5-year overall survival rate was comparable (84.5 versus 87.5 per cent respectively; P = 0.160). Multivariable analysis revealed that type of follow-up was not an independent factor affecting 5-year overall survival. CONCLUSION: Regular follow-up after radical gastrectomy was not associated with improved overall survival.

Cirsium Setidens Water Extracts Containing Linarin Block Estrogen Deprivation-Induced Bone Loss in Mice.

Osteoporosis is evident in postmenopausal women and is an osteolytic disease characterized by bone loss that further increases the susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. Edible Cirsium setidens contains various polyphenols of linarin, pectolinarin, and apigenin with antioxidant and hepatoprotective effects. This study aimed to determine whether Cirsium setidens water extracts (CSEs), the component linarin, and its aglycone acacetin blocked ovariectomy (OVX)-induced bone loss. This study employed OVX C57BL/6 female mice as a model for postmenopausal osteoporosis. CSEs, acacetin, or linarin was orally administrated to OVX mice at a dose of 20 mg/kg for 8 weeks. Surgical estrogen loss in mice for 8 weeks reduced bone mineral density (BMD) of mouse femur and serum 17ß-estradiol level and enhanced the serum receptor activator of NF-κB ligand/osteoprotegerin ratio with uterine atrophy. CSEs and linarin reversed such adverse effects and enhanced femoral BMD in OVX mice. Oral administration of CSEs and linarin attenuated tartrate-resistant acid phosphate activity and the induction of αvß3 integrins and proton suppliers in resorption lacunae in femoral bone tissue of OVX mice. In addition, CSEs and linarin curtailed the bone levels of cathepsin K and matrix metalloproteinase-9 responsible for osteoclastic bone resorption. On the other hand, CSEs and linarin enhanced the formation of trabecular bones in estrogen-deficient femur with increased induction of osteocalcin and osteopontin. Further, treatment with CSEs and linarin enhanced the collagen formation-responsive propeptide levels in the circulation along with the increase in the tissue non-specific alkaline phosphatase level in bone exposed to OVX. Supplementing CSEs, acacetin, or linarin to OVX mice elevated the formation of collagen fibers in OVX trabecular bone, evidenced using Picrosirius red staining. Accordingly, CSEs and linarin were effective in retarding osteoclastic bone resorption and promoting osteoblastic bone matrix mineralization under OVX conditions. Therefore, linarin, which is abundant in CSEs, may be a natural compound for targeting postmenopausal osteoporosis and pathological osteoresorptive disorders.

Risks and benefits of additional surgery for early gastric cancer in the upper third of the stomach meeting non-curative resection criteria after endoscopic submucosal dissection.

BACKGROUND: Additional surgery is recommended after non-curative endoscopic submucosal dissection for early gastric cancer. However, it is not easy to recommend for tumors located in the upper third of the stomach, because it would be a total or proximal gastrectomy. This study aimed to evaluate the actual risks and benefits of additional gastrectomy for upper third tumors. METHODS: We reviewed the clinicopathological data of patients who underwent total or proximal gastrectomy for early gastric cancer in the upper third of the stomach between March 2002 and January 2021. The incidence of lymph node metastasis and postoperative complications were calculated, and risk factors for lymph node metastasis were identified using logistic regression analysis. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: A total of 523 patients underwent total or proximal gastrectomy for early gastric cancer; 379 of them had tumors meeting the non-curative resection criteria for endoscopic submucosal dissection. The overall lymph node metastasis rate was 9.5%, and lymphovascular invasion was the only significant risk factor for lymph node metastasis (p < 0.001). The most common sites of lymph node metastasis were stations 1, 3, and 7, with their rates being 3.2%, 3.7%, and 3.2%, respectively. Overall and severe (Clavien-Dindo grade III or higher) postoperative complication rates were 21.1% and 14.0%, respectively, while postoperative mortality was 0.5% (2/379). The 5-year overall survival rates for patients with and without lymph node metastasis were 96.1% and 81.1%, respectively (p = 0.076). CONCLUSIONS: Before planning an additional gastrectomy after non-curative endoscopic resection for the upper third tumor, we should consider both the benefit of the 9.5% curability for lymph node metastasis and the risks of the 21% postoperative complications and 0.5% mortality.

Aesculetin Accelerates Osteoblast Differentiation and Matrix-Vesicle-Mediated Mineralization.

The imbalance between bone resorption and bone formation in favor of resorption results in bone loss and deterioration of bone architecture. Osteoblast differentiation is a sequential event accompanying biogenesis of matrix vesicles and mineralization of collagen matrix with hydroxyapatite crystals. Considerable efforts have been made in developing naturally-occurring plant compounds, preventing bone pathologies, or enhancing bone regeneration. Coumarin aesculetin inhibits osteoporosis through hampering the ruffled border formation of mature osteoclasts. However, little is known regarding the effects of aesculetin on the impairment of matrix vesicle biogenesis. MC3T3-E1 cells were cultured in differentiation media with 1-10 µM aesculetin for up to 21 days. Aesculetin boosted the bone morphogenetic protein-2 expression, and alkaline phosphatase activation of differentiating MC3T3-E1 cells. The presence of aesculetin strengthened the expression of collagen type 1 and osteoprotegerin and transcription of Runt-related transcription factor 2 in differentiating osteoblasts for 9 days. When ≥1-5 µM aesculetin was added to differentiating cells for 15-18 days, the induction of non-collagenous proteins of bone sialoprotein II, osteopontin, osteocalcin, and osteonectin was markedly enhanced, facilitating the formation of hydroxyapatite crystals and mineralized collagen matrix. The induction of annexin V and PHOSPHO 1 was further augmented in ≥5 µM aesculetin-treated differentiating osteoblasts for 21 days. In addition, the levels of tissue-nonspecific alkaline phosphatase and collagen type 1 were further enhanced within the extracellular space and on matrix vesicles of mature osteoblasts treated with aesculetin, indicating matrix vesicle-mediated bone mineralization. Finally, aesculetin markedly accelerated the production of thrombospondin-1 and tenascin C in mature osteoblasts, leading to their adhesion to preformed collagen matrix. Therefore, aesculetin enhanced osteoblast differentiation, and matrix vesicle biogenesis and mineralization. These findings suggest that aesculetin may be a potential osteo-inductive agent preventing bone pathologies or enhancing bone regeneration.

Dietary Collagen Hydrolysates Ameliorate Furrowed and Parched Skin Caused by Photoaging in Hairless Mice.

Collagen hydrolysates have been suggested as a favorable antiaging modality in skin photoaged by persistent exposure to ultraviolet radiation (UV). The current study evaluated the beneficial effect of collagen hydrolysates (fsCH) extracted from Pangasius hypophthalmus fish skin on wrinkle formation and moisture preservation in dorsal skin of hairless mice challenged with UV-B. Inter-comparative experiments were conducted for anti-photoaging among fsCH, retinoic acid (RA), N-acetyl-D-glucosamine (NAG), and glycine-proline-hydroxyproline (GPH). Treating human HaCaT keratinocytes with 100-200 µg/mL fsCH reciprocally ameliorated the expression of aquaporin 3 (AQP3) and CD44 deranged by UV-B. The UV-B-induced deep furrows and skin thickening were improved in parched dorsal skin of mice supplemented with 206-412 mg/kg fsCH as well as RA and GPH. The UV-B irradiation enhanced collagen fiber loss in the dorsal dermis, which was attenuated by fsCH through enhancing procollagen conversion to collagen. The matrix metalloproteinase expression by UV-B in dorsal skin was diminished by fsCH, similar to RA and GPH, via blockade of collagen degradation. Supplementing fsCH to UV-B-irradiated mice decreased transepidermal water loss in dorsal skin with reduced AQP3 level and restored keratinocyte expression of filaggrin. The expression of hyaluronic acid synthase 2 and hyaluronidase 1 by UV-B was remarkably ameliorated with increased production of hyaluronic acid by treating fsCH to photoaged mice. Taken together, fsCH attenuated photoaging typical of deep wrinkles, epidermal thickening, and skin water loss, like NAG, RA, or GPH, through inhibiting collagen destruction and epidermal barrier impairment.

Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis.

BACKGROUND: Shoulder osteoarthritis is a gradual wearing of the articular cartilage concomitant with degenerative rotator cuff tears (RCTs). This pathologic disorder is related to inflammation, oxidative stress, and angiogenesis. Degenerative alterations may prompt production of cytokines and angiogenesis-related proteins, evoking rotator cuff diseases. This study tested the hypothesis that oxidative stress-responsive mediators can influence joint inflammation of patients with RCT. METHODS: Twelve healthy RCT patients not suffering shoulder osteoarthritis were categorized as the control group, and 24 patients were allocated to 2 RCT groups (RCTP1 and RCTP2), according to severity of RCT and glenohumeral arthritis. Cytokines, growth factors, and angiogenic biomarkers in synovial fluids, blood, platelet-rich plasma (PRP), and tendon tissues were analyzed with enzyme-linked immunosorbent assay, immunoblotting, and collagen zymography. RESULTS: Induction of interleukin 8, tumor necrosis factor α, and interleukin 1ß was considerably elevated in synovial fluids of RCTP groups (P = .0398, P = .0428, P = .0828, respectively). The joint inflammation highly enhanced insulin-like growth factor 1 and transforming growth factor ß1 (TGF-ß1) in the synovial fluids and serum. Angiogenesis-related angiopoietin (Ang) 1 and 2, Tie-2, and hypoxia-inducible factor 1α were upregulated in reactive oxygen species-exposed RCTP synovium (P < .05). The production of matrix metalloproteinase 1 markedly increased in synovial fluids of the RCTP group (P = .043), whereas tissue collagen type I expression diminished with reduction of connective tissue growth factor expression (P = .032). Although the secretion of platelet-derived growth factor AB and vascular endothelial growth factor was marginal in the circulation (P = .714, P = .335), platelet-derived growth factor AB, TGF-ß1, Ang-1, and matrix metalloproteinase 1 were enriched in PRP of the RCTP group (P < .001, P = .002, P = .0389, respectively). CONCLUSIONS: Synovial matrix degradation and oxidative stress-triggered angiogenesis may be involved in inducing RCT with joint inflammation. TGF-ß1, Ang-1, and Ang-2 are the major components to repair RCT and to alleviate joint inflammation in PRP therapy.

Chrysin ameliorates podocyte injury and slit diaphragm protein loss via inhibition of the PERK-eIF2α-ATF-CHOP pathway in diabetic mice.

Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys. Exposure to high glucose (33 mmol/L) caused glomerular podocyte apoptosis in vitro, which was dose-dependently attenuated by nontoxic chrysin (1-20 µmol/L) through reduction of DNA fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl-2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in high glucose-exposed renal podocytes. In diabetic db/db mice, oral administration of chrysin (10 mg·kg-1·d-1, for 10 weeks) significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure, characterized by apoptotic podocytes and foot process effacement. In addition, this compound improved the induction of slit diaphragm proteins podocin/nephrin in the diabetic glomeruli. Exposure to high glucose elevated the unfolded protein response (UPR) to ER stress in renal podocytes, evidenced by up-regulation of PERK-eIF2α-ATF4-CHOP. Chrysin treatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vitro and in vivo. These observations demonstrate that targeting ER stress is an underlying mechanism of chrysin-mediated amelioration of diabetes-associated podocyte injury and dysfunction.

Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 µM suppressed ß-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cµ (PKCµ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCµ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice.

Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, submucosal fibrosis and epithelial shedding. Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF-ß. In the in vitro study, we investigated whether 1-20 µM kaempferol inhibited lipopolysaccharide (LPS)-induced bronchial EMT in BEAS-2B cells. The in vivo study explored demoting effects of 10-20 mg/kg kaempferol on airway fibrosis in BALB/c mice sensitized with ovalbumin (OVA). LPS induced airway epithelial TGF-ß1 signaling that promoted EMT with concurrent loss of E-cadherin and induction of α-smooth muscle actin (α-SMA). Nontoxic kaempferol significantly inhibited TGF-ß-induced EMT process through reversing E-cadherin expression and retarding the induction of N-cadherin and α-SMA. Consistently, OVA inhalation resulted in a striking loss of epithelial morphology by displaying myofibroblast appearance, which led to bronchial fibrosis with submucosal accumulation of collagen fibers. Oral administration of kaempferol suppressed collagen deposition, epithelial excrescency and goblet hyperplasia observed in the lung of OVA-challenged mice. The specific inhibition of TGF-ß entailed epithelial protease-activated receptor-1 (PAR-1) as with 20 µM kaempferol. The epithelial PAR-1 inhibition by SCH-79797 restored E-cadherin induction and deterred α-SMA induction, indicating that epithelial PAR-1 localization was responsible for resulting in airway EMT. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.

Laparoscopy-assisted trans gastric wedge resection: A safe treatment for gastric pyloric liposarcoma: A case report and literature review.

Background: Gastric liposarcoma (GL) is extremely rare and radical surgery has been the conventional treatment, even in small tumors. Laparoscopic wedge resection has been reported worldwide for subepithelial tumors of the stomach. Case presentation: The patient was an asymptomatic 63-year-old man presenting with a subepithelial gastric tumor. The esophagogastroduodenoscopy showed a 3 cm ulcerated soft tumor located in the posterior wall of the antrum just above the pylorus. Two preoperative biopsies were performed with a negative result for malignant neoplasm. Dynamic computerized tomography revealed 35 × 35 mm well-defined pyloric mass with fat density. Despite the difficult location of the tumor, function-preserving surgery was performed. Surgery was initiated by a laparoscopic approach with four trocars. After the dissection of the greater omentum, the greater curvature and the posterior wall of the stomach were exposed. A gastrostomy was performed in the anterior wall of the antrum. Due to the difficulty in identifying the tumor location, a mini-laparotomy was conducted. After assessing the pylorus and section parameters, the tumor was extracted by gastrostomy and resected with a linear stapler. The patient was discharged after five days with no complications. The histological diagnosis was a well-differentiated liposarcoma. Resection margins were clear. The tumor cells tested negative for MDM2. No adjuvant therapy was indicated. The patient is alive without recurrence. Conclusions: Despite its rarity, gastric liposarcoma should be respected for differential diagnosis in submucosal tumors. The main diagnostic method is histological, and surgery is the conventional treatment without yet having a consensus. Minimally invasive wedge resection might be a suitable treatment even if the location is close to the pylorus. Multicenter studies are required to obtain better results in the management of this pathology.

Real-world Nationwide Outcomes of Minimally Invasive Surgery for Advanced Gastric Cancer Based on Korean Gastric Cancer Association-Led Survey.

PURPOSE: The study aimed to investigate real-world surgical outcomes of minimally invasive surgery (MIS) for advanced gastric cancer using Korean Gastric Cancer Association (KGCA)-led nationwide data. MATERIALS AND METHODS: A nationwide survey of patients who underwent surgical treatment for gastric cancer in 2019 was conducted by the KGCA. A total of 14,076 patients from 68 institutions underwent surgery, and 4,953 patients diagnosed with pathological stages IB-III gastric cancer were included. Among them, 1,689 patients who underwent MIS (MIS group) and 1,689 who underwent the open approach (open group) were matched using propensity score in a 1:1 ratio. Surgical outcomes were compared, and multivariate analysis was performed to identify the independent factors for overall morbidity. RESULTS: The MIS group had a lower proportion of D2 lymphadenectomy, total omentectomy, and combined resection. However, the number of harvested lymph nodes was higher in the MIS group. Better surgical outcomes, including less blood loss and shorter hospital stay, were observed in the MIS group, and the overall morbidity rate was significantly lower in the MIS group (17.5% vs. 21.9%, P=0.001). The mortality rates did not differ significantly between the 2 groups. In the multivariate analysis, the minimally invasive approach was a significant protective factor against overall morbidity (odds ratio, 0.799; P=0.006). CONCLUSIONS: Based on the Korean nationwide data, MIS for stage IB-III gastric cancer had better short-term outcomes than the open approach, including lower rates of wound complications, intra-abdominal abscesses, and cardiac problems.

Ellagic acid, a functional food component, ameliorates functionality of reverse cholesterol transport in murine model of atherosclerosis.

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

Resveratrol inhibits IgE-mediated basophilic mast cell degranulation and passive cutaneous anaphylaxis in mice.

Resveratrol is a phytoalexin abundantly found in red grape skin and is effective in antitumor and antiinflammation associated with immune responses. This study investigated whether resveratrol suppressed immunoglobulin (Ig)E-mediated allergic responses and passive cutaneous anaphylaxis (PCA) in rat RBL-2H3 mast cells and in BALB/c mice. The release of ß-hexosaminidase and histamine was enhanced in mast cells sensitized with anti-dinitrophenyl (DNP)-IgE and subsequently stimulated by DNP-human serum albumin (HSA), indicative of mast cell degranulation. When mast cells were pretreated with nontoxic resveratrol at 1-25 µmol/L, such induction was dose dependently diminished. Spleen tyrosine kinase (Syk) and phospholipase Cγ (PLCγ) of sensitized mast cells were activated by stimulation with DNP-HSA antigen, which was dampened by ≥5 µmol/L resveratrol. The phosphorylation of protein kinase C (PKC)µ and PKCθ was attenuated by administering resveratrol to DNP-HSA-exposed mast cells, whereas quiescent PKCζ/λ in sensitized cells was dose-dependently activated by resveratrol. Male BALB/c mice were sensitized for 24 h with DNP-IgE and orally administered with resveratrol 1 h before the DNP-HSA challenge. The histamine concentration was enhanced in sensitized mice challenged to DNP-HSA, which was reversed by administration of 10 mg/kg resveratrol. Additionally, it encumbered the tissue activation of Syk, PLCγ, and PKCµ in antigen-exposed mice. Resveratrol decreased IgE-mediated PCA and alleviated allergic edema of mouse ear and dorsal skin. Mast cell degranulation and allergic inflammation, accompanying the induction of monocyte chemotactic protein-1 and macrophage inflammatory protein-2, were inhibited by supplementing resveratrol to antigen-challenged mice. Resveratrol inhibited mast cell-derived, immediate-type allergic reactions, and these responses of resveratrol suggest possible therapeutic strategies in preventing allergic inflammatory diseases.

Highly water-soluble diacetyl chrysin ameliorates diabetes-associated renal fibrosis and retinal microvascular abnormality in db/db mice.

BACKGROUND/OBJECTIVES: Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization. MATERIALS/METHODS: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks. RESULTS: Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysin-treated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice. CONCLUSION: Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosis-associated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy.

Real-World Compliance of Surgical Treatment According to the Korean Gastric Cancer Guideline 2018: Evaluation From the Nationwide Survey Data 2019 in Korea.

PURPOSE: This study evaluated real-world compliance with surgical treatment according to Korea's gastric cancer treatment guidelines. MATERIALS AND METHODS: The 2018 Korean Gastric Cancer Treatment Guidelines were evaluated using the 2019 national survey data for surgically treated gastric cancer based on postoperative pathological results in Korea. In addition, the changes in surgical treatments in 2019 were compared with those in the 2014 national survey data implemented before the publication of the guidelines in 2018. The compliance rate was evaluated according to the algorithm recommended in the 2018 Korean guidelines. RESULTS: The overall compliance rates in 2019 were 83% for gastric resection extent, 87% for lymph node dissection, 100% for surgical approach, and 83% for adjuvant chemotherapy, similar to 2014. Among patients with pathologic stages IB, II, and III disease who underwent total gastrectomy, the incidence of splenectomy was 8.08%, a practice not recommended by the guidelines. The survey findings revealed that 48.66% of the patients who underwent gastrectomy had pathological stage IV disease, which was not recommended by the 2019 guidelines. Compared to that in 2014, the rate of gastrectomy in stage IV patients was 54.53% in 2014. Compliance rates were similar across all regions of Korea, except for gastrectomy in patients with stage IV disease. CONCLUSIONS: Real-world compliance with gastric cancer treatment guidelines was relatively high in Korea.

Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy.

PURPOSE: This study aimed to compare the long-term functional and patient-reported outcomes between intra-corporeal delta-shaped gastroduodenostomy and gastrojejunostomy after laparoscopic distal gastrectomy for gastric cancer. MATERIALS AND METHODS: We retrospectively reviewed clinicopathological data from 616 patients who had undergone laparoscopic distal gastrectomy for stage I gastric cancer between January 2015 and September 2020. Among them, 232 patients who had undergone delta-shaped anastomosis and another 232 who had undergone Billroth II anastomosis were matched using propensity scores. Confounding variables included age, sex, body mass index, physical status classification, tumor location, and T classification. Postoperative complications, nutritional outcomes, endoscopic findings, and quality of life (QoL) were compared between the 2 groups. RESULTS: No significant differences in postoperative complications or nutritional parameters between the two groups were observed. Annual endoscopic findings revealed more residual food and less bile reflux in the delta group (P<0.001) than in the Billroth II group. Changes of QoL were significantly different regarding emotional function, insomnia, diarrhea, reflux symptoms, and dry mouth (P=0.007, P=0.002, P=0.013, P=0.001, and P=0.03, respectively). Among them, the delta group had worse insomnia, reflux symptoms, and dry mouth within three months postoperatively. CONCLUSIONS: Long-term nutritional outcomes and QoL were comparable between the delta and Billroth II groups. However, more residual food and worse short-term QoL regarding insomnia, reflux symptoms, and dry mouth were observed in the delta group. Longer fasting time before endoscopic evaluation and short-term symptom management would have been helpful for the delta group.

Effect of Vitamin B12 Replacement Intervals on Clinical Symptoms and Laboratory Findings in Gastric Cancer Patients after Total Gastrectomy.

The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice.

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.