• 농업과학연구
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• 제45권4호
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• pp.635-643
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• 2018

Bovine milk is widely consumed by humans and is a primary ingredient of dairy foods. Proteomic approaches have the potential to elucidate complex milk proteins and have been used to study milk of various species. Here, we performed a proteomic analysis using 2-dimensional electrophoresis (2-DE) and matrix assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF MS) to identify whey proteins in bovine milk obtained soon after parturition (bovine early milk). The major casein proteins were removed, and the whey proteins were analyzed with 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The whey proteins (2 mg) were separated by pI and molecular weight across pH ranges of 3.0 - 10.0 and 4.0 - 7.0. The 2-DE gels held about 300 to 700 detectable protein spots. We randomly picked 12 and nine spots that were consistently expressed in the pH 3.0 - 10.0 and pH 4.0 - 7.0 ranges, respectively. Following MALDI-TOF MS analysis, the 21 randomly selected proteins included proteins known to be present in bovine milk, such as albumin, lactoferrin, serum albumin precursor, T cell receptor, polymeric immunoglobulin receptor, pancreatic trypsin inhibitor, aldehyde oxidase and microglobulin. These proteins have major functions in immune responses, metabolism and protein binding. In summary, we herein identified both known and novel whey proteins present in bovine early milk, and our sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed their expression pattern.

• Journal of Gastric Cancer
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• 제20권4호
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• pp.376-384
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• 2020

Purpose: The role of prophylactic abdominal drainage in total gastrectomy is not well-established. This study aimed to evaluate the efficacy of abdominal drainage in the prevention and management of major intra-abdominal complications after total gastrectomy for gastric carcinoma. Materials and Methods: We retrospectively reviewed the data of 499 patients who underwent total gastrectomy for gastric carcinoma in a high-volume institution. The patients were divided into drainage and non-drainage groups and compared for the development and management of major intra-abdominal complications, including anastomotic leak, abdominal bleeding, abdominal infection, and pancreatic fistulas. Results: The drainage group included 388 patients and the non-drainage group included 111 patients. The 2 groups showed no significant differences in clinicopathological characteristics or operative procedures, except for more frequent D2 lymphadenectomies in the drainage group. After surgery, the overall morbidity (drainage group vs. non-drainage group: 24.7% vs. 28.8%, P=0.385) and incidence of major intra-abdominal complications (6.4% vs. 6.3%, P=0.959) did not significantly differ between the two groups. The non-drainage group showed no significant increase in the incidence rate of major intra-abdominal complications in the subgroups divided by age, sex, comorbidity, operative approach, body mass index, extent of lymphadenectomy, and pathological stage. Abdominal drainage had no significant impact on early diagnosis, secondary intervention or reoperation, or recovery from major intra-abdominal complications. Conclusions: Prophylactic abdominal drainage showed little demonstrable benefit in the prevention and management of major intra-abdominal complications of total gastrectomy for gastric carcinoma.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.155-168
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• 2021

Purpose: Previous studies have demonstrated the usefulness of the controlling nutritional status (CONUT) score in nutritional assessment and survival prediction of patients with various malignancies. However, its value in advanced gastric cancer (GC) treated with neoadjuvant chemotherapy and curative gastrectomy remains unclear. Materials and Methods: The CONUT score at different time points (pretreatment, preoperative, and postoperative) of 272 patients with advanced GC were retrospectively calculated from August 2004 to October 2015. The χ² test or Mann-Whitney U test was used to estimate the relationships between the CONUT score and clinical characteristics as well as short-term outcomes, while the Cox proportional hazard model was used to estimate long-term outcomes. Survival curves were estimated by using the Kaplan-Meier method and log-rank test. Results: The proportion of moderate or severe malnutrition among all patients was not significantly changed from pretreatment (13.5%) to pre-operation (11.7%) but increased dramatically postoperatively (47.5%). The pretreatment CONUT-high score (≥4) was significantly associated with older age (P=0.010), deeper tumor invasion (P=0.025), and lower pathological complete response rate (CONUT-high vs. CONUT-low: 1.2% vs. 6.6%, P=0.107). Pretreatment CONUT-high score patients had worse progression-free survival (P=0.032) and overall survival (OS) (P=0.026). Adjusted for pathologic node status, the pretreatment CONUT-high score was strongly associated with worse OS in pathologic node-positive patients (P=0.039). Conclusions: The pretreatment CONUT score might be a straightforward index for immune-nutritional status assessment, while being a reliable prognostic indicator in patients with advanced GC receiving neoadjuvant chemotherapy and curative gastrectomy. Moreover, lower pretreatment CONUT scores might indicate better chemotherapy responses.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.197-206
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• 2021

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was high-expressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.

• Journal of Gastric Cancer
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• 제21권1호
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• pp.30-37
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• 2021

Purpose: While the amylase concentration of the drainage fluid (dAmy) has been reported to be a predictor of postoperative pancreas-related complications (PPRC), the optimal timing for its measurement has not been fully investigated. Materials and Methods: The clinicopathological data of 387 patients who underwent elective gastrectomy for gastric cancer were reviewed. Laboratory data, including dAmy on postoperative days 1 (dAmy1) and 3 (dAmy3), and serum C-reactive protein (sCRP) concentrations on postoperative days 1 (sCRP1) and 3 (sCRP3) were compared between patients with PPRC and without PPRC. Results: Nineteen of the 387 patients (4.9%) developed PPRC. The optimal cutoff values of dAmy1, dAmy3, sCRP1, and sCRP3 were 1514 IU/L, 761 IU/L, 8.32 mg/dL, and 15.15 mg/dL, respectively. The area under the curve of dAmy1 was greater than that of dAmy3 (0.915 vs. 0.826), and that of sCRP3 was greater than that of sCRP1 (0.820 vs. 0.659). In the multivariate analysis, dAmy1 (P<0.001) and sCRP3 (P=0.004) were significant predictors of PPRC, while dAmy3 (P=0.069) and sCRP1 (P=0.831) were not. Thirteen (41.9%) of 31 patients with both dAmy1 ≥1,545 IU/L and sCRP3 ≥15.15 mg/dL had PPRC ≥Clavien-Dindo II. In contrast, among 260 patients with both dAmy1 <1,545 IU/L and sCRP3 <15.15 mg/dL, none developed PPRC. Conclusions: dAmy1 was more useful than dAmy3 in predicting PPRC. The combination of dAmy1 and sCRP3 may be a useful criterion for the removal of drains on postoperative day 3.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.19-27
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• 2022

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

• 한방비만학회지
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• 제21권2호
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• pp.59-68
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• 2021

Objectives: We investigated the effects of Clean-DM4 (C-DM4), a polyherbal extract consisting of Coptidis Rhizoma, Salviae Miltiorrhiza Radix, and Cinnamomi Cortex on high fat diet (HFD)-induced obesity and diabetes in mice. Methods: The C57BL/6 mice (6 weeks) were fed a HFD for 8 weeks and then administrated with C-DM4 extract at 500 mg/kg (p.o.) once daily for 4 weeks. The changes of body weights, calorie intakes, and fasting blood glucose (FBG) levels were measured in mice. The serum levels of glucose, insulin, total cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in mice by enzyme-based assay. It was also observed the histological changes of pancreas, liver, and fat tissues with hematoxylin and eosin (H&E) staining. Results: The increase of calorie intakes and FBG levels in HFD-induced obesity mice was significantly decreased by oral administration of C-DM4 extract. C-DM4 extract administration was significantly reduced the increased levels of glucose, insulin, total cholesterol, AST, and ALT in obesity mice. In addition, C-DM4 extract inhibited lipid droplet accumulation in liver tissues of obesity mice, hyperplasia of pancreatic islets, and enlargement of adipocytes in adipose tissues. Conclusions: Our study indicates that C-DM4 extract could help improve obesity and to prevent diabetes progression.

• 대한본초학회지
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• 제37권4호
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• pp.1-8
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• 2022

Objectives : Dioscorea batas Decaisne (DB) has been known to be good for the digestive system on Eastern Asia. However, the protective effect of DB on acute pancreatitis (AP) has not been studied. In this study, we tried to investigate the protective effect of DB water extract on caerulein-induced AP. Methods : To measure the protective effect of DB on AP, Mice were injected with cholecystokinin analogue caerulein (50 ㎍/kg) hourly for 6 times. DB water extract (200 or 400 mg/kg) or saline (control group) was administered orally 1 h before the first injection of caerulein. The mice were sacrificed at 6 h after the last injection of caerulein. The pancreas tissues and serum samples were immediately taken for further analysis. Results : Administration of DB water extract showed the inhibitory effect on the increase of pancreas weight/body weight ratio, pancreatic histological damage. And the rise of serum lipase level was significantly reduced in DB water extract treatment group during AP in mice. However administration of DB water extract did not show significant reduction in serum amylase level. Also, mRNA levels of pro-inflammatory cytokines Interleukin (IL)-6 and Tumor necrosis factor (TNF)-𝛼 but not IL-1𝛽 were inhibited by administration of DB water extract. Conclusions : Taken together, we found that administration of DB water extract ameliorates the severity of caerulein-induced AP, which suggests the potential to be an effective treatment on AP.

• 대한한의학방제학회지
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• 제30권4호
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• pp.249-257
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• 2022

Objectives : Aquilaria crassna is a traditional herbal medicine, which is used to treat allergies, diabetes, neurological diseases. Recently, Aquilaria crassna extracts have been reported in anti-bacterial and anti-inflammatory activities. In this study, various solvents fraction of Aquilaria crassna were investigated on various physiological activities. Methods : According to the polarity, the solvents fraction of Aquilaria crassna were confirmed through TLC, and the activities of the extracts were confirmed in anti-diabetes, anti-obesity, whitening, anti-gout, and anti-inflammation. Results : TLC results showed that ACM and ACM/E have similar patterns and most of the components were transferred to ACM/E. Treatment with ACM and ACM/E fraction were significantly decreased the generation of NO in lipopolysaccharide (LPS)-stimulated macrophage cells. Analysis of biological activities such as α-glucosidase, protein tyrosine phosphatase (PTP1B), tyrosinase, xanthine oxidase (XO) and pancreatic lipase inhibition, showed that ACM and ACM/E have more inhibitory effects than other fractions. Conclusions : Therefore, the results of the present study clearly demonstrate that Aquilaria crassna and its constituents might be beneficial in the prevention or treatment of immune-regulating effects.