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"Kim, Sun"
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Inhibition of SARS-CoV 3CL protease by flavonoids
There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
Journal Article
SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease
Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.
Journal Article
A short guide to histone deacetylases including recent progress on class II enzymes
The interaction between histones and DNA is important for eukaryotic gene expression. A loose interaction caused, for example, by the neutralization of a positive charge on the histone surface by acetylation, induces a less compact chromatin structure, resulting in feasible accessibility of RNA polymerase and increased gene expression. In contrast, the formation of a tight chromatin structure due to the deacetylation of histone lysine residues on the surface by histone deacetylases enforces the interaction between the histones and DNA, which minimizes the chance of RNA polymerases contacting DNA, resulting in decreased gene expression. Therefore, the balance of the acetylation of histones mediated by histone acetylases (HATs) and histone deacetylases (HDACs) is an issue of transcription that has long been studied in relation to posttranslational modification. In this review, current knowledge of HDACs is briefly described with an emphasis on recent progress in research on HDACs, especially on class IIa HDACs.Cancer: Loosening DNA–Protein interactionsTargeting specific structural and functional features of enzymes involved in regulating the interactions between DNA and the histone proteins associated with it could lead to the development of more effective cancer therapeutics. Histone deacetylases (HDACs), enzymes which remove acetyl groups from histones, make the histones wrap more tightly around the DNA so that it becomes inaccessible to the initial steps in gene expression. Drugs that target these enzymes have shown limited efficacy due to lack of specificity and off-target toxicity. Jeong-Sun Kim at Chonnam National University, Gwangju, and Suk-Youl Park at Pohang Accelerator Laboratory, Pohang University of Science and Technology, South Korea, review the latest knowledge about class II HDACs. They suggest that their unique structural features and low enzymatic activity are important features to consider when designing new, more selective HDAC inhibitors.
Journal Article
الأرض / تأليف سون-هان كيم ؛ رسوم أون-جونغ مين ؛ ترجمة غسان شبارو
يتناول كتاب (الأرض) والذي قام بتأليفه (سون-هان كيم) في حوالي (34) صفحة من القطع المتوسط موضوع (القصص الكورية للأطفال) مستعرضا بعض من المحتويات التالية : الأرض بيت، نظرة داخل وكر النمل، قطارات الأنفاق، كيف تتكون الأحافير، الأرض أم، إنها تحتضن الكثير من النبات في تربتها، كما تحتضن ذاعا الأم الدافئتان أطفالها، بعض الحيوانات تعيش على الأشجار، هنالك حيوانات تعيش في باطن الأرض أيضا، إن الناس يعشون على سطح الأرض أيضا تكبر القرى وتتحول إلى مدن، كيف تكون الفحم الحجري، الأرض تشبه مقبرة كبيرة، مما تتكون الأرض، أن الحياة تدب في الأرض.
Book
A Smart Diaper System Using Bluetooth and Smartphones to Automatically Detect Urination and Volume of Voiding: Prospective Observational Pilot Study in an Acute Care Hospital
Background: Caregivers of patients who wear conventional diapers are required to check for voiding every hour because prolonged wearing of wet diapers causes health problems including diaper dermatitis and urinary tract infections. However, frequent checking is labor intensive and disturbs patients’ and caregivers’ sleep. Furthermore, assessing patients’ urine output with diapers in an acute care setting is difficult. Recently, a smart diaper system with wetness detection technology was developed to solve these issues. Objective: We aimed to evaluate the applicability of the smart diaper system for urinary detection, its accuracy in measuring voiding volume, and its effect on incontinence-associated dermatitis (IAD) occurrence in an acute care hospital. Methods: This prospective, observational, single-arm pilot study was conducted at a single tertiary hospital. We recruited 35 participants aged ≥50 years who were wearing diapers due to incontinence between August and November 2020. When the smart diaper becomes wet, the smart diaper system notifies the caregiver to change the diaper and measures voiding volume automatically. Caregivers were instructed to record the weight of wet diapers on frequency volume charts (FVCs). We determined the voiding detection rate of the smart diaper system and compared the urine volume as automatically calculated by the smart diaper system with the volume recorded on FVCs. Agreement between the two measurements was estimated using a Bland-Altman plot. We also checked for the occurrence or aggravation of IAD and bed sores. Results: A total of 30 participants completed the protocol and 390 episodes of urination were recorded. There were 108 records (27.7%) on both the FVCs and the smart diaper system, 258 (66.2%) on the FVCs alone, 18 (4.6%) on the smart diaper system alone, and 6 (1.5%) on the FVCs with sensing device lost. The detection rate of the smart diaper system was 32.8% (126/384). When analyzing records concurrently listed in both the FVCs and the smart diaper system, linear regression showed a strong correlation between the two measurements (R2=0.88, P<.001). The Bland-Altman assessment showed good agreement between the two measurements, with a mean difference of –4.2 mL and 95% limits of agreement of –96.7 mL and 88.3 mL. New occurrence and aggravation of IAD and bed sores were not observed. Bed sores improved in one participant. Conclusions: The smart diaper system showed acceptable accuracy for measuring urine volume and it could replace conventional FVCs in acute setting hospitals. Furthermore, the smart diaper system has the potential advantage of preventing IAD development and bed sore worsening. However, the detection rate of the smart diaper system was lower than expected. Detection rate polarization among participants was observed, and improvements in the user interface and convenience are needed for older individuals who are unfamiliar with the smart diaper system.
Journal Article
Phantom pain wings = Nalgae hwansangt'ong
\"An iconic figure in the emergence of feminist poetry in South Korea and now internationally renowned, Kim Hyesoon pushes the poetic envelope into the farthest reaches of the lyric universe. In her new collection, Kim depicts the memory of war trauma and the collective grief of parting through what she calls an \"I-do-bird-sequence,\" where \"Bird-human is the 'I.'\" Her remarkable essay \"Bird Rider\" explains: \"I came to write Phantom Pain Wings after Daddy passed away. I called out for birds endlessly. I wanted to become a translator of bird language. Bird language that flies to places I've never been.\" What un- folds is an epic sequence of bird ventriloquy exploring the relentless physical and existential struggles against power and gendered violence in \"the eternal void of grief\" (Victoria Chang, The New York Times Magazine). Through in- tensely rhythmic lines marked by visual puns and words that crash together and then fly away as one, Kim mixes traditional folklore and mythology with contemporary psychodramatic realities as she taps into a cremation ceremony, the legacies of Rimbaud and Yi Sang, a film by Agnès Varda, Francis Bacon's portrait of Pope Innocent X, cyclones, a princess trapped in a hospital, and more. A simultaneity of voices and identities rises and falls, existing and exiting on their delayed wings of pain\"-- Provided by publisher.
Book
An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer
We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as
Tfeb
or
Tfe3
. MSL-7 improves glucose tolerance and β-cell function of
hIAPP
+
mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of
Tfeb
. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.
Islet amyloid polypeptide (IAPP) deposition is associated with islet cell loss in diabetes. Here the authors show that a small molecule autophagy enhancer reduces IAPP accumulation in vitro, and also improves glucose tolerance in
hIAPP
+
mice fed high-fat diet, accompanied by reduced hIAPP accumulation, in vivo.
Journal Article