Expression of Keratin 10 in Rat Organ Surface Primo-vascular Tissues

AbstractThe primo-vascular system is described as the anatomical structure corresponding to acupuncture meridians and has been identified in several tissues in the body, but its detailed anatomy and physiology are not well understood. Recently, the presence of keratin 10 (Krt10) in primo-vascular tissue was reported, but this finding has not yet been confirmed. In this study, we compared Krt10 expression in primo-vascular tissues located on the surface of rat abdominal organs with Krt10 expression on blood and lymphatic vessels. Krt10 protein (approximately 56.5 kDa) was evaluated by western blot analysis and immunohistochemistry. Krt10 (IR) in the primo-node was visualized as patchy spots around each cell or as a follicle-like structure containing a group of cells. Krt10 IR was also identified in vascular and lymphatic tissues, but its distribution was diffuse over the extracellular matrix of the vessels. Thus Krt10 protein was expressed in all three tissues tested, but the expression pattern of Krt10 in primo-vascular tissue differed from those of blood and lymphatic vascular tissues, suggesting that structural and the regulatory roles of Krt10 in primo-vascular system are different from those in blood and lymphatic vessels

P2Y receptor regulation of sodium transport in human mammary epithelial cells

Primary human mammary epithelial (HME) cells were immortalized by stable, constitutive expression of the catalytic subunit of human telomerase. Purinergic receptors were identified by RT-PCR and quantitative RT-PCR from mRNA isolated from primary and immortalized cells grown to confluence on membrane filters. Several subtypes of P2Y receptor mRNA were identified including P2Y1, P2Y2, P2Y4, and P2Y6 receptors. RT-PCR experiments also revealed expression of A2b adenosine receptor mRNA in primary and immortalized cells. Confluent monolayers of HME cells exhibited a basal short-circuit current (Isc) that was abolished by amiloride and benzamil. When monolayers were cultured in the presence of hydrocortisone, mRNA expression of Na+ channel (ENaC) -, β-, and -subunits increased approximately threefold compared with that in cells grown without hydrocortisone. In addition, basal benzamil-sensitive Na+ transport was nearly twofold greater in hydrocortisone-treated monolayers. Stimulation with UTP, UDP, or adenosine 5'-O-(3-thiotriphosphate) (ATPS) produced increases in intracellular calcium concentration that were significantly reduced following pretreatment with the calcium-chelating agent BAPTA-AM. Concentration-response relationships indicated that the rank order of potency for these agonists was UTP > UDP > ATPS. Basolateral stimulation with UTP produced a rapid but transient increase in Isc that was significantly reduced if cells were pretreated with BAPTA-AM or benzamil. Moreover, basolateral treatment with either charybdotoxin or clotrimazole significantly inhibited the initial UTP-dependent increase in Isc and eliminated the sustained current response. These results indicate that human mammary epithelial cells express multiple P2 receptor subtypes and that Ca2+ mobilization evoked by P2Y receptor agonists stimulates Na+ absorption by increasing the activity of Ca2+-activated K+ channels located in the basolateral membrane.This work was partly supported by Korea Research Foundation Grant KRF-005-E00076 (to S. Y. Lee) and National Institutes of Health Grants AI-50494 and DK-74010 (to S. M. O'Grady)

Early countermeasures to COVID-19 at long-term care facilities in Gwangju Metropolitan City, Republic of Korea

Objectives The coronavirus disease 2019 (COVID-19) pandemic has continued since its first detection in the Republic of Korea on January 20, 2020. This study describes the early countermeasures used to minimize the risk of COVID-19 outbreaks during cohort quarantine and compares the epidemiological characteristics of 2 outbreaks in long-term care facilities (LTCFs) in Gwangju Metropolitan City in summer 2020. Methods An epidemiological investigation was conducted via direct visits. We investigated epidemiological characteristics, including incidence, morbidity, and mortality rates, for all residents and staff members. Demographic characteristics were analyzed using a statistical program. Additionally, the method of managing infection in LTCFs is described. Results Residents and caregivers had high incidence rates in LTCF-A and LTCF-B, respectively. LTCF-B had a longer quarantine period than LTCF-A. The attack rate was 20.02% in LTCF-A and 27.9% in LTCF-B. The mortality rate was 2.3% (1/43) in LTCF-B, the only facility in which a COVID-19 death occurred. Conclusion Extensive management requires contact minimization, which involves testing all contacts to mitigate further transmission in the early stages of LTCF outbreaks. The findings of this study can help inform and prepare public health authorities for COVID-19 outbreaks, particularly for early control in vulnerable facilities

Dendrotoxin-κ suppresses tumor growth induced by human lung adenocarcinoma A549 cells in nude mice

Voltage-gated K+ (Kv) channels have been considered to be a regulator of membrane potential and neuronal excitability. Recently, accumulated evidence has indicated that several Kv channel subtypes contribute to the control of cell proliferation in various types of cells and are worth noting as potential emerging molecular targets of cancer therapy. In the present study, we investigated the effects of the Kv1.1-specific blocker, dendrotoxin-κ (DTX-κ), on tumor formation induced by the human lung adenocarcinoma cell line A549 in a xenograft model. Kv1.1 mRNA and protein was expressed in A549 cells and the blockade of Kv1.1 by DTX-κ, reduced tumor formation in nude mice. Furthermore, treatment with DTX-κ significantly increased protein expression of p21Waf1/Cip1, p27Kip1, and p15INK4B and significantly decreased protein expression of cyclin D3 in tumor tissues compared to the control. These results suggest that DTX-κ has anti-tumor effects in A549 cells through the pathway governing G1-S transition

Comparison and analysis of the prevalence of hepatitis C virus infection by region in the Republic of Korea during 2005-2012

Background/AimsThis study compared the prevalence of hepatitis C virus (HCV) infection in the Republic of Korea and estimated the high-risk regions and towns.MethodsNational Health Insurance Service data for 8 years from 2005 to 2012 were used. The subjects of the study had visited medical facilities and been diagnosed with or received treatment for acute or chronic HCV as a primary or secondary disease according to ICD-10 codes of B17.1 or B18.2, respectively. Any patient who received treatment for the same disease multiple times during 1 year was counted as one patient in that year. To correct for the effect of the age structure of the population by year and region, the age-adjusted prevalence was calculated using the direct method based on the registered population in 2010.ResultsThe overall prevalence of HCV infection among Korean adults (>20 years old) increased from 0.14% in 2005 to 0.18% in 2012. The sex-, age-, and region-adjusted prevalence in 2012 was 0.18%. The prevalence was highest in Busan, Jeonnam, and Gyeongnam, and there were towns with noticeably higher prevalences within these regions: Jindo (0.97%) in Jeonnam, Namhae (0.90%) in Gyeongnam, and Seo-gu (0.86%) in Busan.ConclusionsThe prevalence of HCV infection differs by regions as well as towns in the Republic of Korea, and is highest in Busan, Jeonnam, and Gyeongnam. The reasons for the high prevalence in these specific regions should be identified, since this could help prevent HCV infections in the future. In addition, active surveillance and treatment policies should be introduced to stop any further spread of infection in these high-prevalence regions

Infrared spectroscopy characterization of normal and lung cancer cells originated from epithelium

The vibrational spectral differences of normal and lung cancer cells were studied for the development of effective cancer cell screening by means of attenuated total reflection infrared spectroscopy. The phosphate monoester symmetric stretching νs(PO32-) band intensity at ~970 cm-1 and the phosphodiester symmetric stretching νs(PO2-) band intensity at ~1,085 cm-1 in nucleic acids and phospholipids appeared to be significantly strengthened in lung cancer cells with respect to the other vibrational bands compared to normal cells. This finding suggests that more extensive phosphorylation occur in cancer cells. These results demonstrate that lung cancer cells may be prescreened using infrared spectroscopy tools

A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs. © 2021, The Author(s).1

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p