Short‑chain fatty acids (SCFAs; butyrate, propionate and acetate) are metabolites derived from the gut microbiota via dietary fiber fermentation. In colon cancer, treatment with SCFAs, mainly ...butyrate and propionate, suppresses cell proliferation, migration and invasion. Furthermore, although sodium butyrate is known to induce cell apoptosis in lung cancer, the anticancer effects of sodium propionate (SP) on lung cancer are not well understood. In the present study, SP treatment induced cell cycle arrest, especially in the G2/M phase, and cell apoptosis in the H1299 and H1703 lung cancer cell lines. As determined by reverse transcription‑quantitative PCR and western blotting, Survivin and p21 expression levels were significantly affected by SP treatment, suggesting that SP treatment suppressed cell proliferation in these lung cancer cell lines. Thus, it was proposed that the SP‑mediated regulation of Survivin and p21 in lung cancer may be applicable to lung cancer therapy.
Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The ...molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10–200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans.
•This system served as a suitable model for developmental neurotoxicity testing.•Ag NPs induce the apoptosis in human neural cells by ROS generation.•Genes for development of neurons were dysregulated in response to Ag NPs.•Molecular events during early developmental neurotoxicity were proposed.
Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier ...integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.
The diagnosis of Parkinson's disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, ...notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging. Thus, we generated in vitro human intestinal organoids from PD patients and ex vivo mouse small intestinal organoids from aged transgenic mice. Both intestinal organoids (IOs) contained the human
G2019S mutation, which is the most frequent genetic cause of familial and sporadic PD. By conducting comprehensive genomic comparisons with these two types of IOs, we determined that a particular gene, namely, Iroquois homeobox protein 2 (
), showed PD-related expression patterns not only in human pluripotent stem cell (PSC)-derived neuroectodermal spheres but also in human PSC-derived neuronal cells containing dopaminergic neurons. We expected that our approach of using various cell types presented a novel technical method for studying the effects of multi-organs in PD pathophysiology as well as for the development of diagnostic markers for PD.
Crosstalk between intracellular signaling pathways has been extensively studied to understand the pluripotency of human pluripotent stem cells (hPSCs), including human embryonic stem cells and human ...induced pluripotent stem cells (hiPSCs); however, the contribution of NAD(+) -dependent pathways remains largely unknown. Here, we show that NAD(+) depletion by FK866 (a potent inhibitor of NAD(+) biosynthesis) was fatal in hPSCs, particularly when deriving pluripotent cells from somatic cells and maintaining pluripotency. NAD and its precursors (nicotinamide NAM and nicotinic acid) fully replenished the NAD(+) depletion by FK866 in hPSCs. However, only NAM effectively enhanced the reprogramming efficiency and kinetics of hiPSC generation and was also significantly advantageous for the maintenance of undifferentiated hPSCs. Our molecular and functional studies reveal that NAM lowers the barriers to reprogramming by accelerating cell proliferation and protecting cells from apoptosis and senescence by alleviating oxidative stress, reactive oxygen species accumulation, and subsequent mitochondrial membrane potential collapse. We provide evidence that the positive effects of NAM (occurring at concentrations well above the physiological range) on pluripotency control are molecularly associated with the repression of p53, p21, and p16. Our findings establish that adequate intracellular NAD(+) content is crucial for pluripotency; the distinct effects of NAM on pluripotency may be dependent not only on its metabolic advantage as a NAD(+) precursor but also on the ability of NAM to enhance resistance to cellular stress.
Six new flavanones, including sanggenol W (1), morusalnol D-F (2-4) and neovanone A and B (5 and6), and fourteen known compounds were isolated from the methanol extract of the dried root bark of
...using various column chromatographic methods. Their structures were elucidated using spectroscopic methods. The isolated compounds were tested
for LDLR, PCSK9 and IDOL mRNA regulatory activity, and it was found that betulinic acid (13) showed the most potent effect on downregulation of PCSK9 and upregulation of LDLR at both mRNA and protein levels, showing comparable results to berberine, the positive control. In addition, betulinic acid (13) inhibited PCSK9 secretion, indicating its role as a future PCSK9 synthesis inhibitor.
Enhancing cardiomyocyte (CM) maturation by topographical cues is a critical issue in cardiac tissue engineering. Thus far, single‐scale topographies with a broad range of feature shapes and ...dimensions have been utilized including grooves, pillars, and fibers. This study reports for the first time a hierarchical structure composed of nano‐pillars (nPs) on micro‐wrinkles (µWs) for effective maturation of CMs. Through capillary force lithography followed by a wrinkling process, vast size ranges of topographies are fabricated, and the responses of CMs are systematically investigated. Maturation of CMs on the hierarchical structures is highly enhanced compared to a single‐scale topography: cardiac differentiation of H9C2s (rat cardiomyocytes) on the hierarchical topography is ≈ 2.8 and ≈ 1.9 times higher than those consisting of single‐scale µWs and nPs. Both nPs and µWs have important roles in cardiac maturation, and the aspect ratio (height/diameter) of the nPs and the wavelength of the µWs are important in CM maturation. This enhancement is caused by strong focal adhesion and nucleus mediated mechanotransduction of CMs from the confinement effects of the different wavelengths of µWs and the cellular membrane protrusion on the nPs. This study demonstrates how a large family of hierarchical structures is used for cardiac maturation.
The hierarchical structure consisting of nano‐pillar and micro‐wrinkle is developed to mature the cardiomyocytes by the topographical cues. Confined within micro‐wrinkle, the stimulation from nano‐pillar is maximized and focal adhesion is strengthened. Owing to this unique structural effect on the hierarchical structure, the maturation of cardiomyocytes is synergistically enhanced compared to the constituent single‐scale topography.
Accessible summary
What is known on the subject?
Pre‐ and postmenopausal women (PPW) experience changes in physical, psychological and social health. South‐East Asia’s female suicide rate is the ...highest compared with other countries, and the suicide rate of PPW in these countries continues to increase.
The most influential factor in Asian women’s suicidal ideation is family conflict; specifically, if PPW in South Korea cannot express their anger, it results in a culture‐bound syndrome called “Hwa‐Byung.” However, there is a lack of research on Asian PPW.
What the paper adds to existing knowledge?
This study found differences in individual‐ and community‐level factors affecting suicidal ideation between pre‐ and postmenopausal women.
Individual factors that commonly affected suicidal ideation were experiencing violence, stress and depression. Individual factors that affected the suicidal ideation of premenopausal women more than postmenopausal women were religious beliefs, alcohol use and chronic disease.
Community level factors affecting suicidal ideation were locational depression and locational counselling for stress in premenopausal women and locational counselling for depression in postmenopausal women.
What are the implications for practice?
Mental health nurses could help prevent suicide by developing and applying community‐based programmes for PPW, considering the specific socio‐economic and cultural context and characteristics of Asian women.
Mental health nurses could help PPW participate in programmes by preparing various interventions such as case management, personal counselling, physical activity, home‐based mental health services, cognitive behavioural therapy and digital interventions for self‐management.
Mental health nurses need to prepare various methods such as online, offline, individual and group methods to work effectively in any social situation.
Introduction
Pre‐ and postmenopausal women (PPW) experience physical and psychological changes with hormonal changes. Among Asian middle‐aged women, family and culture affect suicidal ideation, and the suicide rate among this population is increasing. There are few existing research on suicidal ideation among Asian PPW.
Aim
We examined individual‐ and community‐level factors that predict suicidal ideation among PPW.
Method
Large‐scale panel data from 5,154 South Korean PPW aged 35–64 years were used in a series of multilevel logistic regression analyses to examine factors associated with suicidal ideation at individual and community levels.
Results
Among premenopausal women, religious beliefs, alcohol use, chronic disease, experience of violence, stress and depression were individual‐level factors. Locational depression and locational counselling for stress were community‐level factors. Among postmenopausal women, experience of violence, stress, depression and perceived health status were individual level factors, and locational counselling for depression was a community level factor.
Discussion
Suicidal ideation among PPW is affected by both individual and community level factors. Nurses must comprehensively determine what risk factors affect suicidal ideation through various intervention methods—including online, offline, individual and group methods—while considering socio‐economic situations.
Implications for Practice
Mental health nurses should provide targeted biopsychosocial interventions targeting psychosocial and physical problems and promoting the use of community resources to reduce PPW’s suicidal ideation.
A growing body of evidence suggests that particulate matter (PM10) enters the gastrointestinal (GI) tract directly, causing the GI epithelial cells to function less efficiently, leading to ...inflammation and an imbalance in the gut microbiome. PM10 may, however, act as an exacerbation factor in patients with inflamed intestinal epithelium, which is associated with inflammatory bowel disease.
The purpose of this study was to dissect the pathology mechanism of PM10 exposure in inflamed intestines.
In this study, we established chronically inflamed intestinal epithelium models utilizing two-dimensional (2D) human intestinal epithelial cells (hIECs) and 3D human intestinal organoids (hIOs), which mimic
cellular diversity and function, in order to examine the deleterious effects of PM10 in human intestine-like
models.
Inflamed 2D hIECs and 3D hIOs exhibited pathological features, such as inflammation, decreased intestinal markers, and defective epithelial barrier function. In addition, we found that PM10 exposure induced a more severe disturbance of peptide uptake in inflamed 2D hIECs and 3D hIOs than in control cells. This was due to the fact that it interferes with calcium signaling, protein digestion, and absorption pathways. The findings demonstrate that PM10-induced epithelial alterations contribute to the exacerbation of inflammatory disorders caused by the intestine.
According to our findings, 2D hIEC and 3D hIO models could be powerful
platforms for the evaluation of the causal relationship between PM exposure and abnormal human intestinal functions.
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