Showing papers by "Won Ho Kim published in 2020"
TL;DR: In this article, the authors summarized the correlations between fine dust exposure and neurological disorders reported so far and make suggestions on the direction future research should take, and concluded that it is necessary to study the air pollution-CNS disease connection with particular care and commitment.
Abstract: Background: It is widely known that the harmful effects of fine dust can cause various diseases. Research on the correlation between fine dust and health has been mainly focused on lung and cardiovascular diseases. By contrast, the effects of air pollution on the central nervous system (CNS) are not broadly recognized. Findings: Air pollution can cause diverse neurological disorders as the result of inflammation of the nervous system, oxidative stress, activation of microglial cells, protein condensation, and cerebral vascular-barrier disorders, but uncertainty remains concerning the biological mechanisms by which air pollution produces neurological disease. Neuronal cell damage caused by fine dust, especially in fetuses and infants, can cause permanent brain damage or lead to neurological disease in adulthood. Conclusion: It is necessary to study the air pollution-CNS disease connection with particular care and commitment. Moreover, the epidemiological and experimental study of the association between exposure to air pollution and CNS damage is critical to public health and quality of life. Here, we summarize the correlations between fine dust exposure and neurological disorders reported so far and make suggestions on the direction future research should take.
67 citations
TL;DR: It is found that selection of therapy based on genetic variants associated with thiopurine-induced leukopenia significantly reduced the proportion of patients with myelosuppression during treatment.
34 citations
TL;DR: It is demonstrated that the CSC-suppressive effect of metformin was associated with AMPK activation/mTOR inhibition and repression of protein prenylation through suppression of mevalonate pathway in colorectal cancer.
Abstract: Metformin is a well-known AMPK (AMP-activated protein kinase) activator that suppresses cancer stem cells (CSCs) in some cancers. However, the mechanisms of the CSC-suppressing effects of metformin are not yet well understood. In this study, we investigated the CSC-suppressive effect of metformin via the mevalonate (MVA) pathway in colorectal cancer (CRC). Two colorectal cancer cell lines, HT29 and DLD-1 cells, were treated with metformin, mevalonate, or a combination of the two. We measured CSC populations by flow cytometric analysis (CD44+/CD133+) and by tumor spheroid growth. The expression of p-AMPK, mTORC1 (pS6), and key enzymes (HMGCR, FDPS, GGPS1, and SQLE) of the MVA pathway was also analyzed. We investigated the effects of metformin and/or mevalonate in xenograft mice using HT29 cells; immunohistochemical staining for CSC markers and key enzymes of the MVA pathway in tumor xenografts was performed. In both HT29 and DLD-1 cells, the CSC population was significantly decreased following treatment with metformin, AMPK activator (AICAR), HMG-CoA reductase inhibitor (simvastatin), or mTOR inhibitor (rapamycin), and was increased by mevalonate. The CSC-suppressing effect of these drugs was attenuated by mevalonate. The results of tumor spheroid growth matched those of the CSC population experiments. Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate. The expression of key MVA pathway enzymes was significantly increased in tumor spheroid culture, and by addition of mevalonate, and decreased upon treatment with metformin, AICAR, or rapamycin. In xenograft experiments, tumor growth and CSC populations were significantly reduced by metformin, and this inhibitory effect of metformin was abrogated by combined treatment with mevalonate. Furthermore, in the MVA pathway, CSC populations were reduced by inhibition of protein prenylation with a farnesyl transferase inhibitor (FTI-277) or a geranylgeranyl transferase inhibitor (GGTI-298), but not by inhibition of cholesterol synthesis with a squalene synthase inhibitor (YM-53601). In conclusion, the CSC-suppressive effect of metformin was associated with AMPK activation and repression of protein prenylation through MVA pathway suppression in colorectal cancer.
26 citations
TL;DR: LP3 had anti-inflammatory effects, with increased induction of regulatory T cells and type 2 helper T cells in splenocytes and restoration of goblet cells accompanied by suppression of proinflammatory cytokine expressions, suggesting that L. plantarum CBT LP3 can be used as a potent immunomodulator, which has significant implications for IBD treatment.
25 citations
TL;DR: It is demonstrated that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling and suggesting that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy.
Abstract: Leptin-deficient and leptin-resistant mice manifest obesity, insulin resistance, and left ventricular hypertrophy (LVH); however, LVH's mechanisms are not fully understood. Cardiac iron dysregulation has been recently implicated in cardiomyopathy. Here we investigated the protective effects of caloric restriction on cardiac remodeling in impaired leptin signaling obese mice. RNA-seq analysis was performed to assess the differential gene expressions in the heart of wild-type and ob/ob mice. In particular, to investigate the roles of caloric restriction on iron homeostasis-related gene expressions, 10-week-old ob/ob and db/db mice were assigned to ad libitum or calorie-restricted diets for 12 weeks. Male ob/ob mice exhibited LVH, cardiac inflammation, and oxidative stress. Using RNA-seq analysis, we identified that an iron uptake-associated gene, transferrin receptor, was upregulated in obese ob/ob mice with LVH. Caloric restriction attenuated myocyte hypertrophy, cardiac inflammation, fibrosis, and oxidative stress in ob/ob and db/db mice. Furthermore, we found that caloric restriction reversed iron homeostasis-related lipocalin 2, divalent metal transporter 1, transferrin receptor, ferritin, ferroportin, and hepcidin expressions in the heart of ob/ob and db/db mice. These findings demonstrate that the cardioprotective effects of caloric restriction result from the cellular regulation of iron homeostasis, thereby decreasing oxidative stress, inflammation, and cardiac remodeling. We suggest that decreasing iron-mediated oxidative stress and inflammation offers new therapeutic approaches for obesity-induced cardiomyopathy.
22 citations
TL;DR: Metformin use was associated with better tumor responses and cancer specific survival, as well as a lower risk of cancer recurrence, in patients with lymph node downstaging after neoadjuvant concurrent chemoradiotherapy in rectal cancer with diabetes.
Abstract: Background Metformin may reduce cancer risk and mortality and improve radiotherapy responses in several malignancies. Objective This study aimed to compare tumor responses and prognoses of metformin and nonmetformin groups of diabetic patients receiving neoadjuvant concurrent chemoradiotherapy for rectal cancer. Design This is a retrospective study. Setting This study was conducted at a single institution in the Republic of Korea. Patients Between January 2000 and November 2017, 104 patients with rectal cancer who were taking diabetes medication and treated with neoadjuvant concurrent chemoradiotherapy followed by radical surgery were reviewed. Patients were divided into those taking (n = 62) and not taking metformin (n = 42). Tumor responses, survival, and other outcomes were analyzed. Main outcome measures Tumor response, rectal cancer-specific survival, and disease-free survival rates were measured. Results Tumor regression grade (p = 0.002), pathological complete response (p = 0.037), and N downstaging (p Limitations This was a small retrospective study conducted at a single institution. Conclusions Metformin use was associated with better tumor responses and cancer-specific survival, as well as a lower risk of cancer recurrence, in patients with diabetes mellitus who had lymph node downstaging after neoadjuvant concurrent chemoradiotherapy in rectal cancer. See Video Abstract at http://links.lww.com/DCR/B185. BENEFICIO EN SUPERVIVENCIA CON METFORMINA A TRAVES DE UNA MEJOR RESPUESTA TUMORAL CON QUIMIORRADIOTERAPIA CONCURRENTE NEOADYUVANTE EN CANCER RECTAL: La metformina puede reducir el riesgo de cancer y la mortalidad y mejorar las respuestas a la radioterapia en varios tumores malignos.Comparar las respuestas tumorales y los pronosticos de los grupos con metformina y sin metformina de pacientes diabeticos que reciben quimiorradioterapia concurrente neoadyuvante para cancer de recto.Estudio retrospectivo.Institucion unica en la Republica de Corea.Se revisaron 104 pacientes entre enero de 2000 y noviembre de 2017, con cancer rectal que tomaban medicamentos para diabetes y que fueron tratados con quimiorradioterapia concurrente neoadyuvante seguida de cirugia radical. Los pacientes se dividieron en aquellos que tomaban (n = 62) y los que no tomaban metformina (n = 42). Se analizaron las respuestas tumorales, la supervivencia y otros resultados.Se midieron las tasas de la respuesta tumoral, la supervivencia especifica de cancer rectal y de la supervivencia libre de enfermedad.El grado de regresion tumoral (p = 0.002), la remision patologica completa (p = 0.037) y la reduccion de la etapa N (p
18 citations
TL;DR: Even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders, and pharmacological inhibition of CYP2E1 by 4-methylpyrazole has therapeutic effects.
Abstract: Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a major ethanol oxidation enzyme, by 4-methylpyrazole (4-MP) has therapeutic effects We found that ethanol consumption (5%) 2 weeks before pregnancy resulted in a decrease in the number of viable fetuses and abnormal fetal development, and these effects were accompanied by impaired maternal glucose homeostasis and hepatic steatosis during pregnancy Neonates of ethanol-fed mice had postnatal macrosomia and significantly decreased growth rates during the lactation period However, treatment with 4-MP, a CYP2E1 inhibitor, markedly ameliorated the reduction in insulin action and glucose disposal responsiveness in the livers of ethanol-fed mice Blockage of CYP2E1 significantly reduced the alteration in hepatic lipid deposition, fatty acid oxidation, mitochondrial energy status, and macrophage infiltration observed in ethanol-fed mice Finally, there was a positive correlation between postnatal macrosomia or growth retardation and increased inflammatory responses Collectively, our study suggests that even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders
18 citations
TL;DR: Energy loss in carbon black (CB) filled vulcanizates can be reduced by decreasing the CB volume fraction, reducing the localized deformation of rubber molecules between low-structure CB fillers as mentioned in this paper.
Abstract: Energy loss in carbon black (CB) filled vulcanizates can be reduced by decreasing the CB volume fraction, reducing the localized deformation of rubber molecules between low-structure CB fillers, an...
18 citations
TL;DR: Assessment of the national colonoscopy volume in Korea over a 12-year period on the basis of a nationwide population-based database found that healthcare resources should be prioritized to allow adequate colonoscopic capacity.
Abstract: Background/Aims: Little is known about the national colo noscopy volume in Asian countries. This study aimed to as sess the national colonoscopy volume in Korea over a 12-year period on the basis of a nationwide population-based database. Methods: We conducted a population-based study for colonoscopy claims (14,511,158 colonoscopies performed on 13,219,781 patients) on the basis of the Ko rean National Health Insurance Service database from 2002 to 2013. The 12-year national colonoscopy burden was analyzed according to patient age, patient sex, and health care facility type. Results: The overall volume of colonoscopy increased 8-fold over the 12-year period. The annual colono scopic polypectomy rate significantly increased in all patient sex and age groups over the 12-years period (all p<0.001). The yearly colonoscopic polypectomy rate for men was sig nificantly increased compared with that for women (2.3% vs 1.7%, p<0.001) and for the screening-age group compared with that for the young-age group (2.0% vs 1.6%, p<0.001). The yearly colonoscopic polypectomy rate relative to the total colonoscopy volume significantly increased in primary, sec ondary, and tertiary facilities by 2.4%, 1.9%, and 1.4% dur ing the 12-year period (all p<0.001). In addition, the annual colonoscopy volume covered by high-volume facilities signifi cantly increased by 1.8% in primary healthcare facilities over the 12-year period (p<0.001). Conclusions: Healthcare re sources should be prioritized to allow adequate colonoscopic capacity, especially for men, individuals in the screening-age group, and at primary healthcare facilities. Cost-effective strategies to improve the quality of colonoscopy may focus on primary healthcare facilities and high-volume facilities in Korea. (Gut Liver 2020;14:338-346)
15 citations
TL;DR: These results serve as a guideline for determining the content and filler type and for setting the cure condition during the design of actual compound formulations to increase the crosslink density of rubber while retaining the necessary mechanical and viscoelastic properties for practical application.
Abstract: The tire industry has shown an increasing demand for the reduction in rolling resistance. Efforts have been made to improve the viscoelastic properties of tire compounds and reduce the weight of tires through optimization of the vulcanizate structure, which has become extremely complex. In this study, vulcanizates using carbon black and silica as binary fillers were prepared at various curing temperatures. Vulcanizate structures with respect to curing temperature were classified according to the chemical crosslink density by sulfur, carbon black bound rubber (i.e., physical crosslink due to carbon black), and silica-silane-rubber network. All properties exhibited a decreasing trend under the application of high curing temperatures, and the decrease in the crosslink density per unit content of filler with an increase in curing temperature was shown to be greater in carbon black than in silica. Mechanical and viscoelastic properties were also measured to evaluate the impact that the compound variates have on tire tread performance. These results serve as a guideline for determining the content and filler type and for setting the cure condition during the design of actual compound formulations to increase the crosslink density of rubber while retaining the necessary mechanical and viscoelastic properties for practical application.
13 citations
TL;DR: H-002119-00-001 is a promising and effective therapeutic agent for the treatment of H. pylori infection and its effects on the inflammation of the gastric mucosa reduced levels of inflammation.
Abstract: New antibacterial treatments against Helicobacter pylori are needed as H. pylori is acquiring antibiotic resistance. β-caryophyllene is a natural bicyclic sesquiterpene, with anti-inflammatory and antimicrobial effects. This study investigates the effects of H-002119-00-001 from β-caryophyllene on the eradication of H. pylori in a mouse model, and its effects on the inflammation of the gastric mucosa. To evaluate the anti-H.pylori efficacy of β-caryophyllene, a total of 160 mice were divided into eight groups (n = 10 each) and were administered different treatments for 2 and 4 weeks. H. pylori eradication was assessed using a Campylobacter-like organism (CLO) test and H. pylori qPCR of the gastric mucosa. The levels of inflammation of gastric mucosa were assessed using histology and immunostaining. H-002119-00-001 decreased bacterial burden in vitro. When H-002119-00-001 was administered to mice once daily for 2 weeks, cure rates shown by the CLO test were 40.0%, 60.0%, and 70.0% in groups 6, 7, and 8, respectively. H. pylori levels in gastric mucosa decreased dose-dependently after H-002119-00-001 treatment. H-002119-00-001 also reduced levels of inflammation in gastric mucosa. H-002119-00-001 improved inflammation and decreased bacterial burden in H. pylori-infected mouse models. H-002119-00-001 is a promising and effective therapeutic agent for the treatment of H. pylori infection.
TL;DR: The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription‐3 and p38/mitogen‐activated protein kinase by their common activator, IL‐22.
Abstract: The enzyme glutathione S-transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Here, we provide a significant insight into the role of GSTT1 in inflammatory bowel disease (IBD). We identified decreased expression of GSTT1 in inflamed colons from IBD patients compared to controls. We intrarectally or intraperitoneally delivered Gstt1 gene to mice with dextran sodium sulfate (DSS)-induced colitis and noted attenuation of colitis through gene transfer of Gstt1 via an IL-22 dependent pathway. Downregulation of GSTT1 by pathogen-associated molecular patterns (PAMPs) of microbes reduced innate defense responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription-3 and p38/mitogen-activated protein kinase by their common activator, IL-22. GSTT1 ameliorated colitis and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerization. Our results provide new insights into GSTT1 mutations that are linked to chronic intestinal inflammation due to its insufficient dimerization and their functional consequences in IBDs.
TL;DR: It was confirmed that sulfur variation influenced the silica–rubber coupling efficiency through increased FRI, and field emission scanning electron microscope images showed that increased FRI contributed to improvements in silica dispersion, abrasion resistance, and energy loss characteristics.
Abstract: The vulcanizate structure of filled compounds is affected by filler–rubber interactions (FRI) and the chemical crosslink density (CCD) of the matrix rubber. In particular, in filled compounds using a silica–silane system, FRIs due to silica–rubber coupling are a major influencing factor for the vulcanizate structure and physical properties. In this study, the effect of sulfur variation on the vulcanizate structure of silica-filled solution styrene–butadiene rubber compounds using a sulfide–silane coupling agent was studied. The vulcanizate structure according to sulfur variation was quantitatively analyzed using the swelling test and Flory–Rehner and Kraus equations. As the sulfur content increased, both FRI and the CCD increased, and it was confirmed that sulfur variation influenced the silica–rubber coupling efficiency through increased FRI. In addition, field emission scanning electron microscope images showed that increased FRI contributed to improvements in silica dispersion, abrasion resistance, and energy loss characteristics.
TL;DR: The coupling agent bis[3-(triethoxysily) is commonly used in silica-filled rubber compounds to hydrophobize the silica surface and improve filler-rubber interaction as discussed by the authors.
Abstract: Silane coupling agents are commonly used in silica-filled rubber compounds to hydrophobize the silica surface and improve filler–rubber interaction. The coupling agent bis[3-(triethoxysily...
TL;DR: Specific combinations of CSC markers and β-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.
Abstract: Purpose Wnt and mammalian target of rapamycin (mTOR) are major molecular signaling pathways associated with the development and progression of tumor, as well as the maintenance and proliferation of cancer stem cells (CSCs), in colorectal cancer (CRC). Identifying patients at risk of poor prognosis is important to determining whether to add adjuvant treatment in stage II CRC and thus improve survival. In the present study, we evaluated the prognostic value of Wnt, mTOR, and CSC markers as survival predictors in stage II CRC. Materials and methods We identified 148 cases of stage II CRC and acquired their tumor tissue. Tissue microarrays for immunohistochemical staining were constructed, and the expressions of CD166, CD44, EphB2, β-catenin, pS6 were evaluated using immunohistochemical staining. Results The expressions of CD166 (p=0.045) and pS6 (p=0.045) and co-expression of pS6/CD166 (p=0.005), pS6/CD44 (p=0.042), and pS6/CD44/CD166 (p=0.013) were negatively correlated with cancer-specific survival. Cox proportional hazard analysis showed the combination of CD166/pS6 [hazard ratio, 9.42; 95% confidence interval, 2.36-37.59; p=0.002] to be the most significant predictor related with decreased cancer-specific survival. In addition, co-expression of CD44/CD166 (p=0.017), CD166/β-catenin (p=0.036), CD44/β-catenin (p=0.001), and CD44/CD166/β-catenin (p=0.001) were significant factors associated with liver metastasis. Conclusion Specific combinations of CSC markers and β-catenin/mTOR signaling could be a significant predictor of poor survival in stage II CRC.
TL;DR: In this paper, the authors investigated silica dispersion, cure behavior, mechanical properties, abrasion characteristics, and viscoelastic properties of three types of WMB blend composites.
TL;DR: There was no significant difference between the fasting and dietary groups in admitted patients with IBD, suggesting that imprudent fasting is not helpful in improving the disease course, and peroral diet should not be avoided unless not tolerated by the patient.
Abstract: Background/Aims: Patients with inflammatory bowel disease (IBD) are usually hospitalized because of aggravated gastroin testinal symptoms. Many clinicians empirically advise these patients to fast once they are admitted. However, there has been no evidence that maintaining a complete bowel rest improves the disease course. Therefore, we aimed to investigate the effects of fasting on disease course in admitted patients with IBD or intestinal Behcet’s disease. Methods: A total of 222 patients with IBD or intestinal Behcet’s disease, who were admitted for disease-related symptoms, were retrospectively analyzed. We divided them into 2 groups: fasting group (allowed to take sips of water but no food at the time of admission) and dietary group (re ceived liquid, soft, or general diet). Results: On admission, 124 patients (55.9%) started fasting and 98 patients (44.1%) started diet immediately. Among patients hospitalized through the emergency room, a significantly higher proportion underwent fast ing (63.7% vs. 21.4%, P<0.001); however, 96.0% of the patients experienced dietary changes. Corticosteroid use (P<0.001; haz ard ratio, 2.445; 95% confidence interval, 1.506-3.969) was significantly associated with a reduction in the disease activity score, although there was no significant difference between the fasting group and the dietary group in disease activity reduction (P=0.111) on multivariate analysis. Conclusions: In terms of disease activity reduction, there was no significant difference be tween the fasting and dietary groups in admitted patients with IBD, suggesting that imprudent fasting is not helpful in improv ing the disease course. Therefore, peroral diet should not be avoided unless not tolerated by the patient. (Intest Res 2020;18:85-95)
TL;DR: Low achieved SBP of less than 120 mmHg but also high BP are associated with risk of adverse cardiovascular event and all-cause death in both elderly and younger patients with a distinct U-shaped relationship.
Abstract: OBJECTIVE The main objective is to assess the appropriate level of achieved SBP and DBP to prevent cardiovascular events. METHODS We used the National Sample Cohort from the National Health Insurance Service in Korea and analyzed data of 44 462 hypertensive patients aged 20--84 years. Achieved SBP and DBP were categorized according to average achieved SBP (<120, 120-129, 130-139, 140-149, and ≥150 mmHg) and DBP (<70, 70-79, 80-89, 90-99, and ≥100 mmHg). We examined the association between achieved BP and composite outcome including cardiovascular death, admission of stroke, myocardial infarction, or heart failure, and all-caused death in elderly aged more than 65 years and in younger patients. RESULTS After a median follow-up of 6.8 years, achieved SBP less than 120 mmHg and at least 150 mmHg in elderly and younger patients, respectively, were significantly associated with a higher risk of composite outcome than achieved SBP of 120-129 mmHg. Cox's proportional hazard analysis showed that the association between achieved SBP and risk of composite outcome and all-cause death had U-shaped relationships and identified a nadir of SBP of 135.6 and 128.9 mmHg, respectively, for composite outcome and 135.1 and 131.4 mmHg, respectively, for all-cause death in elderly and younger patients. CONCLUSION Compared with SBP of 120-129 mmHg, not only low achieved SBP of less than 120 mmHg but also high BP are associated with risk of adverse cardiovascular event and all-cause death in both elderly and younger patients with a distinct U-shaped relationship.
TL;DR: Depletion of coronin 1B by siRNA transfection decreased TNFα-induced apoptosis of HUVECs, as determined by MTT, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3 activity assays, and Immunoprecipitation and in situ proximity ligation assays showed that coronin1B depletion diminished the interaction between TNF α-induced TNF receptor-1-associated death domain
TL;DR: The NCSP for gastric cancer was effective in reducing the mortality of oesophageal cancer, and upper endoscopy was superior to UGIS, which reduced the mortality consistently in all age groups over 50 years, whereas UgIS could not.
Abstract: The aim was to evaluate whether this gastric cancer-screening programme was effective in reducing oesophageal cancer mortality. A population-based retrospective cohort study was conducted using the Korean National Cancer Screening Programme (NCSP) database. The study cohort comprised 16,969 oesophageal cancer patients who had been diagnosed in 2007–2014. We analysed the association between the history of NSCP for gastric cancer and oesophageal cancer mortality. Compared with never-screened subjects, ever-screened subjects had an overall HR for oesophageal cancer mortality of 0.647 (95% CI, 0.617–0.679). According to the time interval since screening, the HRs of death were 0.731 (95% CI, 0.667–0.801) for 6–11 months, 0.635 (95% CI, 0.594–0.679) for 12–23 months, 0.564 (95% CI, 0.522–0.610) for 24–35 months and 0.742 (95% CI, 0.679–0.810) for ≥36 months. According to the last screening modality, the HRs of death were 0.497 (95% CI, 0.464–0.531) for upper endoscopy, and 0.792 (95% CI, 0.749–0.838) for UGIS. Upper endoscopy reduced the mortality consistently in all age groups over 50 years, whereas UGIS could not. The NCSP for gastric cancer was effective in reducing the mortality of oesophageal cancer, and upper endoscopy was superior to UGIS.
TL;DR: It is demonstrated that Parkin is highly expressed in both healthy platelets and diabetic platelets, compared to other mitochondria-enriched tissues such as the heart, muscle, brain, and liver.
Abstract: Increased platelet activation and apoptosis are characteristic of diabetic (DM) platelets, where a Parkin-dependent mitophagy serves a major endogenous protective role. We now demonstrate that Parkin is highly expressed in both healthy platelets and diabetic platelets, compared to other mitochondria-enriched tissues such as the heart, muscle, brain, and liver. Abundance of Parkin in a small, short-lived anucleate cell suggest significance in various key processes. Through proteomics we identified 127 Parkin-interacting proteins in DM platelets and compared them to healthy controls. We assessed the 11 highest covered proteins by individual IPs and confirmed seven proteins that interacted with Parkin; VCP/p97, LAMP1, HADHA, FREMT3, PDIA, ILK, and 14-3-3. Upon further STRING analysis using GO and KEGG, interactions were divided into two broad groups: targeting platelet activation through (1) actions on mitochondria and (2) actions on integrin signaling. Parkin plays an important role in mitochondrial protection through mitophagy (VCP/p97), recruiting phagophores, and targeting lysosomes (with LAMP1). Mitochondrial β-oxidation may also be regulated by the Parkin/HADHA interaction. Parkin may regulate platelet aggregation and activation through integrin signaling through interactions with proteins like FREMT3, PDIA, ILK, and 14-3-3. Thus, platelet Parkin may regulate the protection (mitophagy) and stress response (platelet activation) in DM platelets. This study identified new potential therapeutic targets for platelet mitochondrial dysfunction and hyperactivation in diabetes mellitus.
TL;DR: RAFT ESBR showed 9% better abrasion resistance and 29% better fuel efficiency than ESBR, according to the analysis of the data, and the narrow dispersity can reduce energy loss and positively influence the abrading resistance and fuel efficiency.
Abstract: Tread is an important component that directly affects the performance of passenger car radial (PCR) tires. Styrene-butadiene rubber (SBR) is mainly used for tire tread and it includes solution styrene-butadiene rubber (SSBR) and emulsion styrene-butadiene rubber (ESBR). Although SSBR is mainly used, the manufacturing process for SSBR is more challenging than ESBR, which is environmentally friendly, but has the disadvantage of a broad molecular weight distribution. To overcome this, a reversible addition-fragmentation radical transfer (RAFT) polymerization technique is used in ESBR polymerization. An environmentally friendly RAFT ESBR with a narrow dispersity can be polymerized. Here, carbon black-filled compounds were manufactured while using RAFT ESBR, and their properties were compared to ESBR. The analysis showed a low crosslink density of RAFT ESBR, due to the high polysulfide crosslink structure. We manufactured a carbon black-filled compound with the same crosslink density and structure as the ESBR carbon black-filled compound, and the effect of the dispersity of the base polymer was investigated. RAFT ESBR showed 9% better abrasion resistance and 29% better fuel efficiency than ESBR, according to the analysis of the data. The narrow dispersity can reduce energy loss and positively influence the abrasion resistance and fuel efficiency.
TL;DR: Choi et al. as mentioned in this paper investigated differences in the clinical features between intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) in Korean patients with Crohn's disease.
Abstract: Background: In Crohn’s disease (CD), intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) have a common mechanism of transmural inflammation; however, their manifestation is different. Objective: This study aimed to investigate differences in the clinical features between IA and IP in Korean patients with Crohn’s disease. Design: A retrospective cohort study. Setting: Thirty university hospitals and two local hospitals in Korea. Patients: Patients who were diagnosed with CD between July 1982 and December 2008 were enrolled. Main Outcome Measures: Clinical characteristics of IA and IP. Results: Among 1286 patients with CD, 147 (11.4%) had IA and 83 (6.5%) had IP. IA patients were younger than those of IP (24.2 ± 8.6 vs. 30.4 ± 11.1 years, p = 0.001). Location and behavior were significantly different between IA and IP (p = 0.035 and 0.021). In multivariate analyses, perianal fistula was not associated with increased risk of IA and IP, while intestinal stricture was associated with increased risk of IA (OR: 2.72, p < 0.0001) and IP (OR: 2.76, p < 0.0001). In subgroup analyses, 55 (36.5%) IA patients were diagnosed at the diagnosis of CD, and 92 (63.5%) during follow-up of CD, while 47 (56.6%) IP patients were diagnosed at the diagnosis of CD, and 36 (43.3%) during follow-up of CD. Conclusions: There are several differences in the clinical features of IA and IP in Korean patients with CD. The development mechanism is considered as identical, but further investigation should be needed for clinical implication.
TL;DR: It is proposed that VHL plays an important role in the regulation and maintenance of proper cell growth in metazoans because of the evolutionarily conserved regulation of PI3K–TOR signaling by VHL.
TL;DR: Partial venous occlusion results in an increase of venous oxygen saturation in the ischemic limb, while significant changes in venousoxy saturation are not observed in the control limb.
Abstract: INTRODUCTION A sufficient oxygen supply to ischemic limb tissue is the most important requirement for wound healing and limb salvage. We investigated whether partial venous occlusion in the common iliac vein (CIV) causes a further increase of venous oxygenation in a porcine model of acute hindlimb ischemia. MATERIALS AND METHODS In 7 pigs, the model of acute hindlimb ischemia was created with intra-vascular embolization of the common iliac artery (CIA). The arterial and venous oxygen saturation was evaluated at different moments. Oxygen saturation was evaluated at baseline (T0), just after the arterial embolization (T1), at 10 minutes (T2), at 20 minutes (T3), and at 40 minutes (T4). Next, an intentional partial venous occlusion was achieved by inflating the vascular balloon at the level of the right CIV. Then, blood sampling was repeated at 5 minutes (T5), at 15 minutes (T6), and at 25 minutes (T7). RESULTS The arterial oxygen saturation in the right SFA was similar during all phases. In contrast, after arterial embolization, an immediate reduction of venous oxygen saturation was observed (from 85.57 ± 1.72 at T0 to 71.86 ± 7.58 at T4). After the partial venous occlusion, interestingly, the venous oxygen saturations (T5-T7) were significantly increased, again. The venous oxygen saturations evaluated in the hindlimb ischemia with partial venous occlusion and in the control limb (without partial venous occlusion) were significantly over time. Venous oxygen saturations in the experimental limbs were higher than those in the control limbs (79.28 ± 4.82 vs 59.00 ± 2.82, p-value <0.001, 79.71 ± 4.78 vs 60.00 ± 4.24 at T7, p-value <0.001). CONCLUSIONS Partial venous occlusion results in an increase of venous oxygen saturation in the ischemic limb, while significant changes in venous oxygen saturation are not observed in the control limb. An explanation for this may be that the oxygen consumption in the limb tissue is increased because it gets congested with the partial venous occlusion in the right CIV.
TL;DR: In this paper, the effect of azathioprine/6-mercaptopurine (6-MP) and TNF-α antagonists on abdominal and perianal surgery in Korean patients with Crohn's disease was investigated.
Abstract: Objectives: The incidence of Crohn’s disease and the number of associated surgeries are increasing in Korea. This study investigated the effect of azathioprine/6-mercaptopurine (6-MP) and TNF-α antagonists on abdominal and perianal surgery in Korean patients with Crohn’s disease. Design: A retrospective cohort study. Setting: Data from the Crohn’s Disease Clinical Network and Cohort (CONNECT) were used. Patients with confirmed Crohn’s disease between 1982 and 2008 from 32 hospitals in the Republic of Korea were enrolled. The effect of azathioprine/6-MP on abdominal and perianal surgery was analysed using logistic regression analysis adjusting for age and sex. Participants: In total, 1161 Crohn’s disease patients were included in the Republic of Korea in the surgery (n = 462, male = 339, female = 123) and control groups (n = 699, male = 484, female = 215). Results: In total, 1161 patients were selected, with 462 patients who underwent abdominal (n = 245) or perianal surgery (n = 217). The preoperative usage rates of azathioprine/6-MP were 18.8% and 65.1% (p < 0.0001) in the surgery and control groups, respectively. The preoperative usage rates of TNF-α antagonists were 7.1% and 23.3% (p < 0.0001) in the surgery and control groups, respectively. A multivariate analysis revealed that the preoperative use of azathioprine/6-MP had an odds ratio of 0.094 for all surgeries (95% confidence interval [CI]: 0.070–0.127, p < 0.0001), 0.131 for abdominal surgery (95% CI: 397–1.599, p < 0.0001), and 0.059 for perianal surgery (95% CI: 0.038–0.091, p < 0.0001). The preoperative use of TNF-α antagonists had an odds ratio of 0.225 for all surgeries (95% CI: 0.151–0.335, p < 0.0001), 0.403 for abdominal surgery (95% CI: 0.261–0.623, p < 0.0001), and 0.064 for perianal surgery (95% CI: 0.026–0.160, p < 0.001). Strengths of this study: The study presents new evidence of the reduced risk of surgery following azathioprine use in Crohn’s disease patients. Limitations of this study (1) This was not a controlled prospective study. (2) There was a selection bias specific to the CONNECT cohort. (3) The combination or sequential use of azathioprine/6-MP and TNF-α antagonists was not excluded. Conclusion: Azathioprine/6-MP is significantly associated with a reduced risk of abdominal and perianal surgery in Korean patients with Crohn’s disease.