Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells

AbstractIn vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts. We hypothesized that additional factors regulate erythroblasts, likely through either physical contact or secreted factors. To further elucidate these critical factors, human erythroblasts derived from cord blood were cultured at high density to mimic marrow conditions. This growth condition resulted in a significantly increased erythroid enucleation rate and viability. We found several novel contact-related signals in erythroblasts: intercellular adhesion molecule-4 (ICAM-4) and deleted in liver cancer-1 (DLC-1). DLC-1, a Rho-GTPase-activating protein, has not previously been reported in erythroid cells, but its interaction with ICAM-4 was demonstrated here. We further confirmed the presence of a secreted form of human ICAM-4 for the first time. When soluble ICAM-4 was added to media, cell viability and enucleation increased with decreased nuclear dysplasia, suggesting that ICAM-4 is a key factor in contact between cells. These results highlight potential new mechanisms for autonomous control of erythropoiesis. The application of these procedures to erythrocyte manufacturing could enhance in vitro erythrocyte production for clinical use

Endoscopic Submucosal Dissection of Gastric Epithelial Neoplasms after Partial Gastrectomy: A Single-Center Experience

Aims. To investigate the feasibility and safety of endoscopic submucosal dissection (ESD) of gastric epithelial neoplasms in the remnant stomach (GEN-RS) after various types of partial gastrectomy. Methods. This study included 29 patients (31 lesions) who underwent ESD for GEN-RS between March 2006 and August 2016. Clinicopathologic data were retrieved retrospectively to assess the therapeutic ESD outcomes, including en bloc and complete resection rates and procedure-related adverse events. Results. The en bloc, complete, and curative resection rates were 90%, 77%, and 71%, respectively. The types of previous gastrectomy, tumor size, macroscopic type, and tumor histology were not associated with incomplete resection. Only tumors involving the suture lines from the prior partial gastrectomy were significantly associated with incomplete resection. The procedure-related bleeding and perforation rates were 6% and 3%, respectively; none of the adverse events required surgical intervention. During a median follow-up period of 25 months (range, 6–58 months), there was no recurrence in any case. Conclusions. ESD is a safe and feasible treatment for GEN-RS regardless of the previous gastrectomy type. However, the complete resection rate decreases for lesions involving the suture lines

Characteristics of Soil Heavy Metal Contamination in the Intensive Livestock Farming Watersheds

Soil contamination of agricultural watersheds can increase to deteriorate water quality, human health, crop production and aquatic ecology. In particular, it is important to understand the impacts of soil heavy metal contamination from livestock excretion because the excretion has been gradually increasing due to the rapid growth of the livestock industry. In this study, to analyze the characteristics of soil heavy metal contamination in intensive livestock farming watersheds, we selected intensive livestock farming watersheds where livestock heads and amount of livestock excretion by species were spatiotemporally surveyed. We also investigated the characteristics of five soil heavy metals (As, Cd, Pb, Cu, Zn) contamination. The Cheongmi Stream watershed in Anseong, Kyungi-do and Gwangcheon Stream watershed in Hongseong, Chungcheongbuk-do, Korea were one of the most intensive livestock rearing regions where there were very large amounts of livestock excretion. It was also found that Cu and Zn among heavy metals exceeded the soil contamination concern standard at two of the sampling points in the Gwangcheon Stream watershed. Compared to the national soil measurement network data, it was showed that the concentrations of Cd, Cu, and Zn in the intensive livestock farming areas such as both Cheongmi Stream and Gwangcheon Stream watersheds were higher than in other areas. Thus, we suggested that the soil in intensive farming watersheds was contaminated by heavy metals compared to other areas. Therefore, it is necessary to manage not only livestock excretion, but also animals’ welfare, humans, and the environment to use less heavy metals in their feeds. We also believed that various impacts of livestock excretion on the environment need to be studied soon

Association between dyslipidemia and asthma in children: a systematic review and multicenter cohort study using a common data model

Background The association between dyslipidemia and asthma in children remains unclear. Purpose This study investigated the association between dyslipidemia and cholesterol levels in children. Methods A systematic literature review was performed to identify studies investigating the association between dyslipidemia and asthma in children. The PubMed database was searched for articles published from January 2000–March 2022. Data from a cohort study using electronic health records from 5 hospitals, converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM), were used to identify the association between total cholesterol (TC) levels and asthma in children. This cohort study used the Cox proportional hazards model to examine hazard ratio (HR) of asthma after propensity score matching, and included an aggregate meta-analysis of HR. Results We examined 11 studies reporting an association between dyslipidemia and asthma in children. Most were cross-sectional; however, their results were inconsistent. In OMOP-CDM multicenter analysis, the high TC (>170 mg/dL) group included 29,038 children, while the normal TC (≤170 mg/dL) group included 88,823 children including all hospital datasets. In a meta-analysis of this multicenter cohort, a significant association was found between high TC levels and later development of asthma in children <15 years of age (pooled HR, 1.30; 95% confidence interval, 1.12–1.52). Conclusion Elevated TC levels in children may be associated with asthma

Three-dimensional evaluation of soft tissue change gradients after mandibular setback surgery in skeletal Class III malocclusion

Objective: To evaluate whether mandibular setback surgery (MSS) for Class III patients would produce gradients of three-dimensional (3D) soft tissue changes in the vertical and transverse aspects. Materials and Methods: The samples consisted of 26 Class III patients treated with MSS using bilateral sagittal split ramus osteotomy. Lateral cephalograms and 3D facial scan images were taken before and 6 months after MSS, and changes in landmarks and variables were measured using a Rapidform 2006. Paired and independent t-tests were performed for statistical analysis. Results: Landmarks in the upper lip and mouth corner (cheilion, Ch) moved backward and downward (respectively, cupid bow point, 1.0 mm and 0.3 mm, P <.001 and P < 01; alar curvature-Ch midpoint, 0.6 mm and 0.3 mm, both P <.001; Ch, 3.4 mm and 0.8 mm, both P < <.001). However, landmarks in stomion (Stm), lower lip, and chin moved backward (Stm, 1.6 mm; labrale inferius [Li], 6.9 mm; LLBP, 6.9 mm; B9, 6.7 mm; Pog9, 6.7 mm; Me9, 6.6 mm; P < 001, respectively). Width and height of upper and lower lip were not altered significantly except for a decrease of lower vermilion height (Stm-Li, 1.7 mm, P <.001). Chin height (B9-Me9) was decreased because of backward and upward movement of Me9 (3.1 mm, P<.001). Although upper lip projection angle and Stm-transverse projection angle became acute (ChRt-Ls-ChLt, 5.7° Ch Rt-Stm-ChLt, 6.4°, both P, <.001) because of the greater backward movement of Ch than Stm, lower lip projection angle and Stm-vertical projection angle became obtuse (ChRt-Li-ChLt, 10.8°; Ls- Stm-Li, 23.5°, both P <.001) because of the larger backward movement of Li than labrale superius (Ls). Conclusions: Three-dimensional soft tissue changes in Class III patients after MSS exhibited increased gradients from upper lip and lower lip to chin as well as from Stm to Ch

Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin

AbstractEndothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp–EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingo-oophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review

Regulation of autophagic cell death by glycogen synthase kinase-3 beta in adult hippocampal neural stem cells following insulin withdrawal

Background: Neural stem cells (NSCs) hold great potential for the treatment of neurodegenerative diseases. However, programmed cell death (PCD) provoked by the harsh conditions evident in the diseased brain greatly undermines the potential of NSCs. Currently, the mechanisms of PCD that effect NSCs remain largely unknown. Results: We have previously reported that hippocampal neural stem (HCN) cells derived from the adult rat brain undergo autopahgic cell death (ACD) following insulin withdrawal without hallmarks of apoptosis despite their normal apoptotic capabilities. In this study, we demonstrate that glycogen synthase kinase 3β (GSK-3β) induces ACD in insulin-deprived HCN cells. Both pharmacological and genetic inactivation of GSK-3β significantly decreased ACD, while activation of GSK-3β increased autophagic flux and caused more cell death without inducing apoptosis following insulin withdrawal. In contrast, knockdown of GSK-3α barely affected ACD, lending further support to the critical role of GSK-3β. Conclusion: Collectively, these data demonstrate that GSK-3β is a key regulator of ACD in HCN cells following insulin withdrawal. The absence of apoptotic indices in GSK-3β-induced cell death in insulin-deprived HCN cells corroborates the notion that HCN cell death following insulin withdrawal represents the genuine model of ACD in apoptosis-intact mammalian cells and identifies GSK-3β as a key negative effector of NSC survival downstream of insulin signaling. © 2015 Ha et al.; licensee BioMed Central.1