Lineage commitment and tumorigenesis, traits distinguishing stem cells, have not been well characterized and compared in mesenchymal stem cells derived from human dental pulp (DP-MSCs) and bone ...marrow (BM-MSCs). Here, we report DP-MSCs exhibit increased osteogenic potential, possess decreased adipogenic potential, form dentin pulp-like complexes, and are resistant to oncogenic transformation when compared to BM-MSCs. Genome-wide RNA-seq and differential expression analysis reveal differences in adipocyte and osteoblast differentiation pathways, bone marrow neoplasm pathway, and PTEN/PI3K/AKT pathway. Higher PTEN expression in DP-MSCs than in BM-MSCs is responsible for the lineage commitment and tumorigenesis differences in both cells. Additionally, the PTEN promoter in BM-MSCs exhibits higher DNA methylation levels and repressive mark H3K9Me2 enrichment when compared to DP-MSCs, which is mediated by increased DNMT3B and G9a expression, respectively. The study demonstrates how several epigenetic factors broadly affect lineage commitment and tumorigenesis, which should be considered when developing therapeutic uses of stem cells.
While the mainstream discourses of global climate strikes focus on the issue of generational justice, the experience in the context of East Asia has been under-researched. This study explores the ...local experience and interpretation of this movement among the young activists in Taiwan. The results show that climate strike is currently impossible in Taiwan. This study discusses this from the intersectionality of age and culture, namely, obsession with academic performance, low awareness of the right to strike, and parental intervention. It also highlights the strategies that young activists employ to reduce these barriers.
A very large grey area exists between translational stem cell research and applications that comply with the ideals of randomised control trials and good laboratory and clinical practice and what is ...often referred to as snake-oil trade. We identify a discrepancy between international research and ethics regulation and the ways in which regulatory instruments in the stem cell field are developed in practice. We examine this discrepancy using the notion of ‘national home-keeping’, referring to the way governments articulate international standards and regulation with conflicting demands on local players at home.
Identifying particular dimensions of regulatory tools – authority, permissions, space and acceleration – as crucial to national home-keeping in Asia, Europe and the USA, we show how local regulation works to enable development of the field, notwithstanding international (i.e. principally ‘western’) regulation. Triangulating regulation with empirical data and archival research between 2012 and 2015 has helped us to shed light on how countries and organisations adapt and resist internationally dominant regulation through the manipulation of regulatory tools (contingent upon country size, the state's ability to accumulate resources, healthcare demands, established traditions of scientific governance, and economic and scientific ambitions).
•Rather than ethical or rogue, the stem cell therapy field is a complex grey area.•Wealth conditions the affordability of standards and stem cell strategies.•Governments create different regulatory spaces for experimental research.•Regulation for stem cell therapies can be designed to gain a competitive edge.•Local and global stem cell organisations resist and undermine dominant ones.
The Wharton's jelly of the umbilical cord contains mucoid connective tissue and fibroblast‐like cells. Using flow cytometric analysis, we found that mesenchymal cells isolated from the umbilical cord ...express matrix receptors (CD44, CD105) and integrin markers (CD29, CD51) but not hematopoietic lineage markers (CD34, CD45). Interestingly, these cells also express significant amounts of mesenchymal stem cell markers (SH2, SH3). We therefore investigated the potential of these cells to differentiate into cardiomyocytes by treating them with 5‐azacytidine or by culturing them in cardiomyocyte‐conditioned medium and found that both sets of conditions resulted in the expression of cardiomyocyte markers, namely N‐cadherin and cardiac troponin I. We also showed that these cells have multilineage potential and that, under suitable culture conditions, are able to differentiate into cells of the adipogenic and osteogenic lineages. These findings may have a significant impact on studies of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering by helping to eliminate worrying ethical and technical issues.
The aim was to first investigate the efficacy of a preoperative weight management program centered on orlistat, which is mechanistically similar to gastrointestinal bypass procedures in that it ...restricts dietary fat absorption, and then assess its impact on the results of one-anastomosis gastric bypass (OAGB).
We retrospectively reviewed the clinical data of consecutive patients aged 20-65 years with a body mass index (BMI) ≥ 42.5 kg/m2 who underwent primary OAGB from 2014 to 2020. Eligible patients who adhered to a 10-14 day orlistat regimen as part of a 4-6-week diet/lifestyle modification plan preceding surgery were stratified into weight reduction (Group 1) and weight gain (Group 2) groups post treatment. The correlation between pre- and postoperative weight loss and perioperative outcomes was assessed.
Of 62 eligible patients, 55 met the inclusion criteria and complied with treatment; 35 (64%) patients in Group 1 lost a median of 2.0 kg, and Group 2 had a median weight gain of 2.9 kg. Group 1 had a significantly higher initial BMI (48.9 kg/m2 vs. 44.6 kg/m2; p = 0.003), more females (54% vs. 25%) and a shorter operation time than Group 2 (107 min vs. 140 min; p = 0.109). There was no difference in the incidence of 30-day complications. Weight loss did not differ between the groups at 24 months.
Effective weight control through an orlistat-containing regimen benefitted two-thirds of patients who underwent OAGB; however, further weight loss was not observed at 2 years post-surgery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Environmental Sociology has addressed gender, racial, and class dynamics within environmental movements, but the involvement of children, particularly in East Asia, remains under-researched. This ...article examines the representations of children in the news articles of Taiwanese anti-nuclear movements. With critical discourse analysis, the study examines 154 newspaper articles from two major newspapers published between 1987 and 2019. This article characterizes the representations of children in the news in three types: as slogans, as silent participants, and as defenders of rights. The paper shows that children have been reported in the news articles since the inception of the anti-nuclear movements, but their opinions were only recently reported. Dismissing children's voices in the news articles could be related to undermining children's capacity and agency to form views. The shifting representations of children in the news articles symbolize evolving power relations between children and adults, which are fluid, dynamic, and diverse rather than static. This article calls for a reflection on how children are represented in mass media and how the representations reveal the underlying presumption of children by adults.
Introduction
Early leakage detection following bariatric procedures is crucial, but a standardized evaluation method is lacking. The aim was to validate the potential benefits of postoperative day 1 ...(POD1) C-reactive protein (CRP) levels and white blood cell (WBC) counts in distinguishing at-risk patients following Roux-en-Y gastric bypass (RYGB) while considering the impact of obesity-related chronic inflammation.
Methods
Retrospective analysis of 261 consecutive patients aged 18–65 years with a body mass index (BMI) of 32.5–50 kg/m
2
who underwent primary RYGB between 2017 and 2022. Sequential changes in CRP levels and WBC counts measured 48 h preoperatively and on POD1 morning were collected and compared between patients with/without complications and in patients without complications stratified by preoperative CRP levels.
Results
Female patients and those with a higher BMI tended to have higher baseline CRP levels, which were positively related to postoperative CRP. Patients experiencing complications had higher WBC counts and a higher prevalence of WBC counts >14,000/μl (77.8% vs. 25.4%;
p
<0.001) than those without complications. Baseline CRP ≥ 0.3 mg/dl, a longer operative time, and blood loss >10 ml were significantly more common with WBC counts above 14,000/μl; a reasonable range of change in WBC count (∆WBC) derived from its positive correlation to postoperative WBC count (
r
=0.6695) may serve as a useful complementary indicator.
Conclusion
An individualized CRP threshold setting and integrated interpretation of the WBC count can be more appropriate than using static criteria for differentiating at-risk patients after RYGB. Further studies are needed to validate these findings and determine their generalizability.
Graphical abstract
Purpose
This study aimed to identify factors that hinder 24-h patient discharge after laparoscopic Roux-en-Y gastric bypass (LRYGB) in a low-volume practice.
Material and Methods
Consecutive patients ...who fulfilled regional criteria and underwent primary LRYGB from 2018 to 2020 were retrospectively analyzed. Patients were discharged on the morning of the first postoperative day (POD1) after meeting the predefined criteria. The assessed outcome measures (POD1 vital signs, laboratory findings, pain scores and nausea/vomiting) and 30-day postoperative complications were compared between the early (stay ≤ 24 h) and delayed (>24 h) groups.
Results
For 107 patients who fulfilled the inclusion criteria, 48 (44.9%) were discharged within 24 h. There were no differences in the baseline demographics, except that the early group was more likely to have a previous abdominal operation (35.4% vs. 16.9%). Both groups had similar operation durations (89 min vs. 92 min), but the early group had a markedly shortened length of stay (23 (24–22) h vs. 27 (47–26) h). The POD1 parameters were the same between the groups, except that the delay group had a significantly higher visual analog scale score, with fewer patient scores of 0. Patients who were younger and female were more likely to need additional IV analgesics. No POD1 antiemesis was required throughout the study. There was no increase in the 30-day complications.
Conclusion
Patient discharge at 24 h post-LRYGB is feasible and safe in a low-volume practice. A more comprehensive pain relief strategy may be required before generalizing this approach.
Graphical abstract
Microsatellite-instable (MSI), a predictive biomarker for immune checkpoint blockade (ICB) response, is caused by mismatch repair deficiency (MMRd) that occurs through genetic or epigenetic silencing ...of MMR genes. Here, we report a mechanism of MMRd and demonstrate that protein phosphatase 2A (PP2A) deletion or inactivation converts cold microsatellite-stable (MSS) into MSI tumours through two orthogonal pathways: (i) by increasing retinoblastoma protein phosphorylation that leads to E2F and DNMT3A/3B expression with subsequent DNA methylation, and (ii) by increasing histone deacetylase (HDAC)2 phosphorylation that subsequently decreases H3K9ac levels and histone acetylation, which induces epigenetic silencing of MLH1. In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Human cancer cell lines and tissue array effectively confirm these signaling pathways. These data indicate the dual involvement of PP2A inactivation in silencing MLH1 and inducing MSI.
Articular cartilage has a very limited capacity for self-repair, and mesenchymal stem cells (MSCs) have the potential to treat cartilage defects and osteoarthritis. However, in-depth mechanistic ...studies regarding their applications are required. Here we demonstrated the use of chitosan film culture for promoting chondrogenic differentiation of MSCs. We found that MSCs formed spheres 2 days after seeding on dishes coated with chitosan. When MSCs were induced in a chondrogenic induction medium on chitosan films, the size of the spheres continuously increased for up to 21 days. Alcian blue staining and immunohistochemistry demonstrated the expression of chondrogenic proteins, including aggrecan, type II collagen, and type X collagen at 14 and 21 days of differentiation. Importantly, chitosan, with a medium molecular weight (size: 190–310 kDa), was more suitable than other sizes for inducing chondrogenic differentiation of MSCs in terms of sphere size and expression of chondrogenic proteins and endochondral markers. We identified that the mechanistic target of rapamycin (mTOR) signaling and its downstream S6 kinase (S6K)/S6 were activated in chitosan film culture compared to that of monolayer culture. The activation of mTOR/S6K was continuously upregulated from days 2 to 7 of differentiation. Furthermore, we found that mTOR/S6K signaling was required for chondrogenic differentiation of MSCs in chitosan film culture through rapamycin treatment and mTOR knockdown. In conclusion, we showed the suitability of chitosan film culture for promoting chondrogenic differentiation of MSCs and its potential in the development of new strategies in cartilage tissue engineering.
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