Gingival Fibroblasts as a Promising Source of Induced Pluripotent Stem Cells

Induced pluripotent stem (iPS) cells efficiently generated from accessible tissues have the potential for clinical applications. Oral gingiva, which is often resected during general dental treatments and treated as biomedical waste, is an easily obtainable tissue, and cells can be isolated from patients with minimal discomfort.We herein demonstrate iPS cell generation from adult wild-type mouse gingival fibroblasts (GFs) via introduction of four factors (Oct3/4, Sox2, Klf4 and c-Myc; GF-iPS-4F cells) or three factors (the same as GF-iPS-4F cells, but without the c-Myc oncogene; GF-iPS-3F cells) without drug selection. iPS cells were also generated from primary human gingival fibroblasts via four-factor transduction. These cells exhibited the morphology and growth properties of embryonic stem (ES) cells and expressed ES cell marker genes, with a decreased CpG methylation ratio in promoter regions of Nanog and Oct3/4. Additionally, teratoma formation assays showed ES cell-like derivation of cells and tissues representative of all three germ layers. In comparison to mouse GF-iPS-4F cells, GF-iPS-3F cells showed consistently more ES cell-like characteristics in terms of DNA methylation status and gene expression, although the reprogramming process was substantially delayed and the overall efficiency was also reduced. When transplanted into blastocysts, GF-iPS-3F cells gave rise to chimeras and contributed to the development of the germline. Notably, the four-factor reprogramming efficiency of mouse GFs was more than 7-fold higher than that of fibroblasts from tail-tips, possibly because of their high proliferative capacity.These results suggest that GFs from the easily obtainable gingival tissues can be readily reprogrammed into iPS cells, thus making them a promising cell source for investigating the basis of cellular reprogramming and pluripotency for future clinical applications. In addition, high-quality iPS cells were generated from mouse GFs without Myc transduction or a specific system for reprogrammed cell selection

Divergent Synthesis of Lamellarin α 13-Sulfate, 20-Sulfate, and 13,20-Disulfate

A divergent synthesis of three sulfate derivatives of lamellarin α, namely, lamellarin α 13-sulfate (2), 20-sulfate (1), and 13,20-disulfate (4) has been achieved via a common intermediate (6) in which 13-OH and 20-OH of the lamellarin core are differentially protected by MOM and benzyl groups, respectively. Compound (6) in turn was prepared using sequential Suzuki-Miyaura coupling of 3,4-dihydroxypyrrole bistriflate (7) as a key reaction

Primary Diaphragmatic Dedifferentiated Liposarcoma in a Young Female Patient after Delivery

A 26-year-old woman was admitted with the chief complaint of chest pain. She had delivered her first child 9 months before admission. Computed tomography showed a bulky mass in her left chest, and histopathological analysis revealed it to be dedifferentiated liposarcoma. We initiated doxorubicin chemotherapy, and the tumor mass reduced. After that, we performed vascular embolization along with chemotherapy, but tumor size did not reduce. On the 160th day of illness, the patient died. This is the first report of a primary diaphragmatic dedifferentiated liposarcoma diagnosed after delivery. Establishment of a regimen of chemotherapy for bulky unresectable liposarcoma is necessary

Characteristics of patients with chronic idiopathic interstitial pneumonia undergoing repeated respiratory-related hospitalizations: A retrospective cohort study.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease. Chronic idiopathic interstitial pneumonia (c-IIP) is a group of lung diseases consisting mainly of fibrotic IIPs, and IPF is a type of c-IIP. Some patients with c-IIP undergo respiratory-related hospitalizations (RHs). With the hypothesis that the characteristics of patients who undergo RHs are related to the number of hospitalizations, we reviewed and investigated the RHs of patients with c-IIP.MethodsWe retrospectively examined the data of patients with c-IIP who were admitted to Kindai University Hospital between January 2008 and December 2018 for respiratory-related causes.ResultsDuring the study period, 243 patients with c-IIP were hospitalized a total of 544 times because of respiratory-related causes. The most common reasons for the first RH were acute exacerbation (48.1%) followed by pulmonary infection (32.5%). The most frequent reason for subsequent RHs was pulmonary infection. The in-hospital and 90-day mortality rate of patients with pulmonary infection increased with increasing numbers of RHs. Patients with multiple RHs had significantly worse long-term survival than patients hospitalized a single time.ConclusionsPulmonary infection was the most frequent reason for repeated RHs. The proportion of all patients hospitalized for pulmonary infection at each RH increased with increasing numbers of RHs, along with the mortality rate of patients with pulmonary infections. Furthermore, repeated RHs were associated with poor survival

The utility of the Japanese Association for Acute Medicine DIC scoring system for predicting survival in acute exacerbation of fibrosing idiopathic interstitial pneumonia.

BackgroundAlthough evidence of a disseminated intravascular coagulation (DIC)-like reaction has been identified in the lung parenchyma of patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF), an association between DIC and IPF outcome has not been elucidated. Therefore, we retrospectively investigated the association between the Japanese Association for Acute Medicine (JAAM)-DIC score and mortality in patients with acute exacerbation of fibrosing idiopathic interstitial pneumonia (AE-fIIP).MethodsBetween January 2008 and December 2016, consecutive patients with chronic fIIP who were admitted for the first time for AE-fIIP were recruited into the study. Associations between clinical data and JAAM-DIC score at the time of admission and mortality were examined.ResultsDuring the study period, a total of 91 patients with fIIP (73.0±8.4 y.o.) were hospitalized for AE-fIIP for the first time. The 30-day and hospital mortality were 8.7% and 17.5%, respectively. A multivariate analysis showed that the JAAM-DIC score on admission was an independent predictor of 30-day mortality (odds ratio [OR] 2.57, 95% confidential interval [CI] 1.50-4.40, P = 0.0006). The APACHE II score (OR 1.29, 95% CI 1.01-1.63, P = 0.03) and the JAAM-DIC score (OR 3.47, 95% CI 1.73-6.94, P = 0.0004) were independent predictors of hospital mortality.ConclusionsThe JAAM-DIC scoring system can predict survival in patients with AE-fIIP. The role of DIC in the pathogenesis of AE-fIIP merits further investigation

HFpEF without elevated right ventricular systolic pressure is a favorable prognostic indicator in patients with IPF requiring hospitalization for heart failure.

BackgroundSome patients with idiopathic pulmonary fibrosis (IPF) must be hospitalized because of heart failure (HF), including HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF). The association between IPF and HF has not been clarified. We retrospectively investigated the clinical features and outcomes of patients with IPF who required nonelective hospitalization because of HF.MethodsWe examined data from IPF patients who required nonelective hospitalization for HF at the Kindai University Hospital from January 2008 to December 2018. We divided the patients into 3 groups: those with HFpEF without elevated right ventricular systolic pressure (RVSP), those with HFpEF and elevated RVSP, and those with HFrEF. The recurrence rates of HF after discharge and the 30- and 90-day mortality rates of the patients were evaluated.ResultsDuring the study period, 37 patients with IPF required hospitalization because of HF. Among the 34 patients included in the study, 17 (50.0%) were diagnosed with HFpEF without elevated RVSP, 11 (32.3%) with HFpEF and elevated RVSP, and 6 (17.6%) with HFrEF. Patients with HFrEF had significantly higher values for B-type natriuretic peptide (BNP) and left ventricular (LV) end-systolic and end-diastolic diameters than patients with the 2 types of HFpEF (BNP: P = 0.01 and P = 0.0004, LV end-systolic diameter: P ConclusionsAmong patients with IPF, HFpEF without elevated RVSP was the most common type of HF that required hospitalization. Patients with HFpEF without elevated RVSP survived longer than the patients with the other 2 types of HF

Cell-Based Double-Screening Method to Identify a Reliable Candidate for Osteogenesis-Targeting Compounds

Small-molecule compounds strongly affecting osteogenesis can form the basis of effective therapeutic strategies in bone regenerative medicine. A cell-based high-throughput screening system might be a powerful tool for identifying osteoblast-targeting candidates; however, this approach is generally limited with using only one molecule as a cell-based sensor that does not always reflect the activation of the osteogenic phenotype. In the present study, we used the MC3T3-E1 cell line stably transfected with the green fluorescent protein (GFP) reporter gene driven by a fragment of type I collagen promoter (Col-1a1GFP-MC3T3-E1) to evaluate a double-screening system to identify osteogenic inducible compounds using a combination of a cell-based reporter assay and detection of alkaline phosphatase (ALP) activity. Col-1a1GFP-MC3T3-E1 cells were cultured in an osteogenic induction medium after library screening of 1280 pharmacologically active compounds (Lopack1280). After 7 days, GFP fluorescence was measured using a microplate reader. After 14 days of osteogenic induction, the cells were stained with ALP. Library screening using the Col-1a1/GFP reporter and ALP staining assay detected three candidates with significant osteogenic induction ability. Furthermore, leflunomide, one of the three detected candidates, significantly promoted new bone formation in vivo. Therefore, this double-screening method could identify candidates for osteogenesis-targeting compounds more reliably than conventional methods