This study aims to elucidate the effects that staying home due to COVID-19 has had on households with primary school-age children living in the central area. To determine the differences in states of ...mind between people in the central area and people in other areas, we investigated the changes in their "daily lives" including matters related to school; playing outside; associating with other children; "communication" including communication with family and friends; and the "use of information technologies" that secure communication. Moreover, we explored households that are satisfied even when they are unable to go out and clarified how children and their parents who live in the central area perceive the current situation. The study results indicate that the risks of COVID-19 in large cities have spatial characteristics and increase the burden on households raising children. Particularly in the central area, which has a high population density, the changes children experience are striking. Furthermore, due to the inadequate amount of open space, a strong awareness of the "new normal (avoiding the "Three Cs" (closed spaces, crowded places, and close-contact settings)" is required.
Purpose
Resveratrol is a well‐known potent activator of sirtuin‐1 (SIRT1). We investigated the direct effects of hypoxia and resveratrol on SIRT1/ peroxisome proliferator‐activated receptor‐gamma ...coactivator 1α (PGC‐1α) pathways, vascular endothelial growth factor (VEGF), hypoxia‐inducible factor (HIF)‐1α, and mitochondrial quantity in a steroidogenic human ovarian granulosa‐like tumor cell line (KGN) cells.
Methods
KGN cells were cultured with cobalt chloride (CoCl2; a hypoxia‐mimicking agent) and/or resveratrol. The mRNA and protein levels, protein secretion, and intracellular localization were assessed by real‐time PCR, Western blot analysis, ELISA, and immunofluorescence staining, respectively. Mitochondrial quantity was measured based on the mitochondrial DNA (mtDNA) copy number.
Results
CoCl2 simultaneously attenuated the levels of SIRT1 and mtDNA expression, and induced the levels of VEGF protein production. In contrast, resveratrol significantly increased the levels of SIRT1 and mtDNA copy number, but reduced VEGF production in normoxia. Resveratrol could recover CoCl2‐suppressed SIRT1 and mtDNA expression and antagonize CoCl2‐induced VEGF production. CoCl2 treatment resulted in a downregulation of PGC‐1α expression, and this effect was recovered by resveratrol. Resveratrol significantly suppressed the production of the CoCl2‐induced HIF‐1α and VEGF proteins.
Conclusion
These results suggest that resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway and inhibits VEGF induction through HIF‐1α under hypoxic conditions.
Resveratrol improves mitochondrial quantity by activating the SIRT1/PGC‐1α pathway in hypoxia. PGC‐1α was strong and predominantly localized to the nucleus of the cells treated with resveratrol. CoCl2‐reduced PGC‐1α mRNA and protein expression was recovered by resveratrol.
Cyclic changes of the human endometrium, such as proliferation, secretion, and decidualization, occur during regular menstrual cycles. Heart– and neural crest derivatives–expressed transcript 2 ...(HAND2) is a key transcription factor in progestin-induced decidualization of human endometrial stromal cells (ESCs). It has been suggested that HAND2 regulates interleukin 15 (IL15), a key immune factor required for the activation and survival of uterine natural killer (uNK) cells. Activated uNK cells can promote spiral artery remodeling and secrete cytokines to induce immunotolerance. To date, no studies have evaluated the transcription factors that regulate IL15 expression in human ESCs. In the present study, we examined whether HAND2 controls IL15 transcriptional regulation in human ESCs. Quantitative RT-PCR and histological analyses revealed that HAND2 and IL15 levels increase considerably in the secretory phase of human endometrium tissues. Results from ChIP-quantitative PCR suggested that HAND2 binds to a putative HAND2 motif, which we identified in the upstream region of the human IL15 gene through in silico analysis. Using a luciferase reporter assay, we found that the upstream region of the human IL15 gene up-regulates reporter gene activities in response to estradiol and a progestin representative (medroxyprogesterone) in ESCs. The upstream region of the human IL15 gene also exhibited increasing responsiveness to transfection with a HAND2 expression vector. Of note, deletion and substitution variants of the putative HAND2 motif in the upstream region of IL15 did not respond to HAND2 transfection. These findings confirm that HAND2 directly up-regulates human IL15 transcription in ESCs.
Abstract
Endometrial stromal cells differentiate into decidual cells through the process of decidualization. This differentiation is critical for embryo implantation and the successful establishment ...of pregnancy. Recent epidemiological studies have suggested that thyroid hormone is important in the endometrium during implantation, and it is commonly believed that thyroid hormone is essential for proper development, differentiation, growth, and metabolism. This study aimed to investigate the impact of thyroid hormone on decidualization in human endometrial stromal cells (hESCs) and define its physiological roles in vitro by gene targeting. To identify the expression patterns of thyroid hormone, we performed gene expression profiling of hESCs during decidualization after treating them with the thyroid hormone levothyroxine (LT4). A major increase in decidual response was observed after combined treatment with ovarian steroid hormones and thyroid hormone. Moreover, LT4 treatment also affected the regulation of many transcription factors important for decidualization. We found that type 3 deiodinase, which is particularly important in fetal and placental tissues, was upregulated during decidualization in the presence of thyroid hormone. Further, it was observed that progesterone receptor, an ovarian steroid hormone receptor, was involved in thyroid hormone–induced decidualization. In the absence of thyroid hormone receptor (TR), due to the simultaneous silencing of TRα and TRβ, thyroid hormone expression was unchanged during decidualization. In summary, we demonstrated that thyroid hormone is essential for decidualization in the endometrium. This is the first in vitro study to find impaired decidualization as a possible cause of infertility in subclinical hypothyroidism (SCH) patients.
Purpose
To elucidate the effects of cigarette smoking on human endometrial maturation for reproductive function, the authors examined the in vitro effects of cigarette smoke extract (CSE) on ...angiogenesis and decidualization in primary human endometrial stromal cells (ESCs).
Methods
Endometrial stromal cells were cultured with CSE and/or estradiol‐17β (E2) and medroxyprogesterone acetate (MPA). The mRNA, protein levels, and protein secretion of the angiogenic factors and decidual specific factors were assessed using real‐time polymerase chain reaction, Western blot analysis, and enzyme‐linked immunosorbent assay, respectively. Decidualization was also monitored by the changes in cellular morphology.
Results
Endometrial stromal cell proliferation substantially decreased after dose‐dependent treatments with CSE at concentrations above 1%, whereas cell death was induced at treatment concentrations above 1% CSE. Treatments above 0.025% CSE led to increased vascular endothelial growth factor mRNA through hypoxia‐inducible factor‐1α accumulation. CSE concentrations at 0.01% and 0.025% increased the prolactin expression levels after treatment with E2 and MPA, whereas 0.1% and 0.25% CSE concentrations suppressed prolactin. Similar tendencies were observed in cellular morphology and other decidual specific factors.
Conclusion
These results suggest that exposure to cigarette smoke affects endometrial appropriate maturation including the processes of angiogenesis and decidualization in the reproductive system.
Chitooligosaccharides exhibit several biomedical activities, such as inflammation and tumorigenesis reduction in mammals. The mechanism of the chitooligosaccharides' formation in vivo has been, ...however, poorly understood. Here we report that mouse acidic chitinase (Chia), which is widely expressed in mouse tissues, can produce chitooligosaccharides from deacetylated chitin (chitosan) at pH levels corresponding to stomach and lung tissues. Chia degraded chitin to produce
-acetyl-d-glucosamine (GlcNAc) dimers. The block-type chitosan (heterogenous deacetylation) is soluble at pH 2.0 (optimal condition for mouse Chia) and was degraded into chitooligosaccharides with various sizes ranging from di- to nonamers. The random-type chitosan (homogenous deacetylation) is soluble in water that enables us to examine its degradation at pH 2.0, 5.0, and 7.0. Incubation of these substrates with Chia resulted in the more efficient production of chitooligosaccharides with more variable sizes was from random-type chitosan than from the block-type form of the molecule. The data presented here indicate that Chia digests chitosan acquired by homogenous deacetylation of chitin in vitro and in vivo. The degradation products may then influence different physiological or pathological processes. Our results also suggest that bioactive chitooligosaccharides can be obtained conveniently using homogenously deacetylated chitosan and Chia for various biomedical applications.
Purpose
To study the association between stromal cell‐derived factor‐1 (SDF‐1/CXCL12) and vascular endothelial growth factor (VEGF) concentrations in individual human ovarian follicles and IVF ...outcomes.
Methods
Concentrations of SDF‐1 and VEGF in 261 follicular fluid samples were measured with enzyme‐linked immunosorbent assay. IVF outcome parameters were included in fertilization rate, cleavage rate, embryo morphology on day 3, and blastocyst morphology on day 5.
Results
The follicular concentration of SDF‐1 and VEGF was not significantly associated with fertilization and cleavage outcome, and embryo morphology. The rates of full blastocysts and good‐quality blastocysts were significantly higher in follicles with an SDF‐1 concentration of 275‐350 pg/mL than in the follicles with SDF‐1 concentrations of <200 and ≥350 pg/mL (P < 0.05). The follicular concentration of VEGF was not associated with the blastocyst morphology.
Conclusion
Our findings showed that follicular concentration of SDF‐1, and not VEGF, may be a valuable biochemical marker of blastocyst development.
The study aimed to elucidate the glycolytic metabolism of human endometrial stromal cells (hESCs) in hypoxic environment.
The hESCs were cultured in hypoxic environment, and their metabolic pathways ...were analyzed using metabolomics. We assessed glucose uptake using 2-deoxyglucose (2-DG) assay. The expression of glucose transporters (GLUTs) required for glucose uptake was determined using real-time quantitative polymerase chain reaction (qPCR) and western blotting. Furthermore, we knocked down GLUT1 and examined the uptake of 2-DG.
Under hypoxia, glucose-6-phosphate, fructose-6-phosphate, and fructose-1,6-diphosphate were significantly elevated in hESCs (P < 0.05). This finding indicated enhancement in glycolysis. The volume of glucose uptake increased significantly under hypoxia (P < 0.05). Hypoxia simultaneously induced the expression of GLUT1 and GLUT3 mRNA (P < 0.05) and attenuated the expression of GLUT8 (P < 0.05). Glucose uptake was significantly inhibited upon knockdown of GLUT1 (P < 0.0001).
These results demonstrated a very important role of glucose transport under hypoxia. Also, hESCs utilize glycolysis to adapt to hypoxic conditions that could occur in menstrual and implantation period. These findings pave the way to study implantation failure and tumors originating from the endometrium.
Cell biology; Biological sciences; Molecular biology; Cell Culture; Metabolomics; Oxidative Stress; Reproductive System; Women's Health; endometrium; hypoxia; glycolysis; glucose transporter; human endometrial stromal cells
To report the case of a patient with pseudoxanthoma elasticum (PXE) and proliferative diabetic retinopathy (PDR), and discuss the relationship between PXE and diabetic retinopathy (DR).
A 47-year-old ...man with PXE presented with angioid streaks and DR in both eyes, and bilateral panretinal photocoagulation was performed for treatment. Vitrectomy had previously been performed in his right eye for vitreous hemorrhage due to PDR. Systemic findings included multiple, discrete, symmetrical, small yellow papules bilaterally in the axilla and inguinal region. Examination on presentation showed vitreous hemorrhage in his left eye, and vitrectomy was performed for treatment. Intraoperative findings showed fibrovascular membrane around the optic disc and vascular arcade. A mottled fundus (peau d'orange appearance) associated with angioid streaks was also present, yet there was no evident choroidal neovascularization (CNV). The postoperative course was satisfactory, and corrected visual acuity improved from 0.02 to 0.7 diopters.
Despite the peau d'orange appearance in both eyes of this case, no CNV was evident. The vitreous hemorrhage was thus attributed to PDR. Moreover, we reviewed the published literature and discuss the relationship between PXE and DR.
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