DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming

BACKGROUND AND METHODS: In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC). Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions. CONCLUSIONS/SIGNIFICANCE: Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy

Computed Tomography in Pulmonary Tuberculosis

CT scans in patients with primary tuberculosis commonly show findings of Iympho-hematogeneous spread of the disease, while those of reactivation tuberculosis commonly show findings of bronchogenic spread. Typical CT findings of primary tuberculosis are airspace consolidation of the middle and lower lobes with mediastinal and hilar lymphadenopathy showing central lower attenuation and peripheral rim en- . hancement. Typical CT findings of reactivation tuberculosis are nodular and linear pulmonary lesions at the apex without lymphadenopathy. High-resolution CT is extremely helpful in understanding the patho-morphologic changes, mode of spread of the disease, sequential morphologic change after antituberculous chemotherapy, and possibly in diagnosing activity of the disease. Centrilobular small nodule or branching linear lesions are the most common findings of fresh active pulmonary tuberculosis, which represent intra- and peri-bronchiolar caseation necrosis. CT is also useful in the evaluation of longstanding destructive pulmonary lesions and tracheobronchial tuberculosis. The importance of the role of CT scan in patients with pulmonary tuberculosis is increasing

DEL 적혈구에 의한 항-D 동종면역

Extremely weak D variants called DEL are serologically detectable only by adsorption-elution techniques. A nucleotide change of exon 9 in RHD gene, RHD (K409K, 1227G>A) allelic variant is present in almost all the DEL individuals of East Asians. No DEL phenotype has yet been shown to induce a primary alloanti-D immunization in East Asia. A 68-yr-old D-negative Korean man was negative for anti-D at admission, and he developed alloanti-D after transfusion of red blood cells (RBC) from 4 apparently D-negative donors. Four donors who typed D-negative by routine serologic test were analyzed by real-time PCR for RHD gene and RHD (K409K). One donor was found to have RHD (K409K), This is the first case in which DEL RBCs with RHD (K409K) induced a primary alloanti-D immunization in Asian population. Because the DEL phenotype can induce an anti-D immunization in D-negative recipients, further discussion is needed whether RhD negative donors should be screened by molecular method and what an efficient genotyping method is for detecting the RHD gene carriers in Korea. (Korean J Lab Med 2009;29:361-5)Polin H, 2009, TRANSFUSION, V49, P676, DOI 10.1111/j.1537-2995.2008.02046.xFlegel WA, 2009, TRANSFUSION, V49, P465, DOI 10.1111/j.1537-2995.2008.01975.xSun CF, 2008, ANN CLIN LAB SCI, V38, P258Richard M, 2007, TRANSFUSION, V47, P852, DOI 10.1111/j.1537-2995.2007.01199.xLuettringhaus TA, 2006, TRANSFUSION, V46, P2128, DOI 10.1111/j.1537-2995.2006.01042.xYasuda H, 2005, TRANSFUSION, V45, P1581, DOI 10.1111/j.1537-2995.2005.00579.xWagner T, 2005, TRANSFUSION, V45, P520Gassner C, 2005, TRANSFUSION, V45, P527Kim JY, 2005, TRANSFUSION, V45, P345WAGNER FF, 2001, BMC GENET, V2, P10Avent ND, 2000, BLOOD, V95, P375Aubin JT, 1997, BRIT J HAEMATOL, V98, P356Okuda H, 1997, J CLIN INVEST, V100, P373Avent ND, 1997, BLOOD, V89, P2568HWANG YS, 1996, KOREAN J BLOOD TRANS, V7, P233DANIELS G, 1995, HUMAN BLOOD GROUPSMAK KH, 1993, TRANSFUSION, V33, P348LINCHU M, 1988, TRANSFUSION, V28, P350

MiR-9 Controls Chemotactic Activity of Cord Blood CD34⁺ Cells by Repressing CXCR4 Expression

Improved approaches for promoting umbilical cord blood (CB) hematopoietic stem cell (HSC) homing are clinically important to enhance engraftment of CB-HSCs. Clinical transplantation of CB-HSCs is used to treat a wide range of disorders. However, an improved understanding of HSC chemotaxis is needed for facilitation of the engraftment process. We found that ectopic overexpression of miR-9 and antisense-miR-9 respectively down- and up-regulated C-X-C chemokine receptor type 4 (CXCR4) expression in CB-CD34＋ cells as well as in 293T and TF-1 cell lines. Since CXCR4 is a specific receptor for the stromal cell derived factor-1 (SDF-1) chemotactic factor, we investigated whether sense miR-9 and antisense miR-9 influenced CXCR4-mediated chemotactic mobility of primary CB CD34＋ cells and TF-1 cells. Ectopic overexpression of sense miR-9 and antisense miR-9 respectively down- and up-regulated SDF-1-mediated chemotactic cell mobility. To our knowledge, this study is the first to report that miR-9 may play a role in regulating CXCR4 expression and SDF-1-mediated chemotactic activity of CB CD34＋ cells

CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs

The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO–K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. V max in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO–K1 cells, while K m values were similar in all cases. The uptake of β -lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO–K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO–K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as β -lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, l -dopa and α -methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34496/1/11_ftp.pd

Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

PurposeB cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naïve cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children.MethodsOne hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects.ResultsAsthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; P=0.011]. Sputum BAFF positively correlated with sputum eosinophils (γ=0.406, P<0.001) and sputum ECP (γ=0.789, P<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (γ=-0.291, P<0.001) or post-bronchodilator FEV1 (γ=-0.334, P<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP.ConclusionThese findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation

Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019

Background This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated. Methods We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM. Results The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002. Conclusion The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone

PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1−/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1−/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.So-Young Lee received National Research Foundation Grant of Korea (NRF2019R1A2C4070492), funded by the Korean government (https://www.nrf.re.kr) for this work. Soonchul Lee received National Research Foundation Grant of Korea (NRF-2019R1C1C1004017), funded by the Korean government (https://www.nrf.re.kr) for this work

The relationship between childhood asthma and socioeconomic status: a Korean nationwide population-based study

PurposeThis study aimed to investigate associations of socioeconomic status (SES) with asthma exacerbation and asthma-related hospital utilization factors among children with asthma in the Republic of Korea.MethodsThis study retrospectively analyzed population-level data from the Korean National Health Insurance Service, collected from 2013 through 2019. SES was classified into five categories according to the national health insurance premiums quantiles (0 [lowest] to 4 [highest]). The hazard ratios (HRs) for asthma exacerbation, emergency department (ED) visits, hospital admission, and intensive care unit (ICU) admission were analyzed with respect to SES.ResultsAmong the five SES groups, SES group 0 (medical aid), had the highest tallies and proportions of children who experienced asthma exacerbations (n = 1,682, 4.8%), ED visits (n = 932, 2.6%), hospital admission (n = 2,734, 7.7%) and ICU admission (n = 14, 0.04%). Compared with SES group 4, SES group 0 had adjusted HRs of 3.73 (p = 0.0113) and 1.04 (p &lt; 0.0001) for ventilator support/tracheal intubation and administration of systemic corticosteroids, respectively. Relative to group 4, the adjusted HRs for ED visits, hospital admission, and ICU admission in group 0 were 1.88 (p &lt; 0.0001), 2.20 (p &lt; 0.0001), and 7.12 (p &lt; 0.0001), respectively. In the survival analysis, group 0 had a significantly higher risk of ED presentation, hospital admission, and ICU admission than the other groups (log-rank p &lt; 0.001).ConclusionCompared with children of higher SES, those in the lowest SES group had increased risk of asthma exacerbation, hospital admission, and receiving treatment for severe asthma symptoms

Hepatic Splenosis Preoperatively Diagnosed as Hepatocellular Carcinoma in a Patient with Chronic Hepatitis B: A Case Report

We report on a case of hepatic splenosis. A 32-yr-old man underwent a splenectomy due to trauma at the age of 6. He had been diagnosed as being a chronic hepatitis B-virus carrier 16 yr prior to the surgery. The dynamic computer tomography (CT) performed due to elevated serum alpha-fetoprotein (128 ng/mL) demonstrated two hepatic nodules, which were located near the liver capsule. A nodule in Segment IVa had a slight enhancement during both the arterial and portal phases, and another nodule in Segment VI showed a slight enhancement only in the portal phases. Dynamic magnetic resonance imaging (MRI) of the mass in Segment VI showed enhanced development in the arterial phases and slight hyperintensivity to the liver parenchyma in the portal phases. These imaging findings suggested a hypervascular tumor in the liver, which could be either focal nodular hyperplasia, adenoma, or hepatocellular carcinoma (HCC). Even though these lesions were diagnosed as HCC, some of the findings were not compatible with typical HCC. On dynamic CT and MRI, all lesions showed a slight arterial enhancement and did not show early venous washout. All lesions were located near the liver capsule. These findings, along with a history of splenectomy, suggested a diagnosis of hepatic splenosis