BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

BACKGROUND: Embryo-endometrium cross-talk is one of the critical processes for implantation, and unsuccessful cross-talk leads to infertility. We established an endometrium-embryo (or embryoid bodies, hEBs) in vitro model in 2D and 3D conditions and assessed its potential through the fusion of embryos and the expression of specific markers. METHODS: C57BL/6 mouse embryos and human embryoid body (hEB) derived from embryonic stem cells were prepared as embryo models. Mouse endometrium (EM) and human endometrium cell line, HEC-1-A, were prepared, and 2D or 3D EMs were generated. The viability of the 3D endometrium was analyzed, and the optimal ratio of the gelation was revealed. The invasion of the embryos or hEBs was examined by immunostaining and 3D image rendering. RESULTS: The embryos and the alternative hEBs were effectively fused into 2D or 3D vitro EM models in both mouse and human models. The fused embryos and hEBs exhibited migration and further development. Notably, the established in vitro model expressed Oct4 and E-Cadherin, markers for early embryonic development; human CG Receptor and Progesterone Receptor, critical for implantation and pregnancy maintenance; and TSH Receptor, Epiregulin, and Prolactin, indicators of endometrial receptivity and embryo implantation. CONCLUSION This study marks a significant advancement in the field, as we have successfully established a novel in vitro model for studying embryo-endometrium cross-talk. This model, a crucial tool for understanding fertility and the causes of miscarriage due to failed implantation, provides a unique platform for investigating the complex processes of successful implantation and pregnancy, underscoring its potential impact on reproductive health.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Background and Objectives: This study aimed to investigate the protective effect of polydeoxyribonucleotide (PDRN) against skin flap necrosis in a murine skin flap model.Materials and Method Twenty mice with rectangular skin flaps on the dorsum were randomly divided into the PDRN (n=10) and pentobarbital sodium (PBS) (n=10) injection groups. PDRN (8 mg/kg) was subdermally injected at 12 different points immediately after the operation. After 7 days, the flap perfusions were evaluated using a laser speckle contrast imaging (LSCI) system, and specimens were collected for immunohistochemistry analysis. Results: The percentage of survival area relative to the total flap area was significantly higher in the PDRN group (60.87%±7.63%) than in the PBS group (45.23%±10.72%) (p<0.05). The mean LSCI perfusion signal of the distal part of the skin flap in the PBS group was 0.57±0.12, and that in the PDRN group was 0.74±0.13 (p<0.05). The PDRN group had a significantly lower interleukin 1 beta expression than the PBS group and higher vascular endothelial growth factor α expression than the PBS group (p<0.05). Conclusion These findings suggest that subdermally injected PDRN is more effective in enhancing flap survival during necrosis.

Background/Aims: Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. Methods: Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. Results: Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. Conclusions The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

This study was performed to evaluate the effect of cyclic precalcification treatment on the improvement of bioactivity of Ti-6Al-4V mini-screws. The cutted plate-shaped specimens of 10 mm × 10 mm dimensions, and a mini-screw with a diameter of 1.6 mm × 6.0 mm in length were used. Anodic oxidation treatment was carried out in a glycerol electrolyte solution containing 20 wt% H2O and 1.5 wt% NH 4F. Voltage of 20 V with current density of 20 mA/cm2 was applied for 1 hour to form a nanotube TiO2 layer. Afterwards, to improve the bioactivity, specimens were immersed in 0.5 vol% silica aqueous solution at 37 ℃ for 5 minutes, and then cyclic precalcification treatment with 0.05 M NH 4H2PO4and 0.01 M Ca(OH)2 solution at 90 ℃ was repeated with 20 times. Based on surface treatment the experimental groups were divided into three groups, namely untreated group (UT), anodized and heat-treated group (AH), and anodized, silica-treated, cyclic precalcified and heat-treated group (ASPH). There were TiO2 nanotubes completely self-aligned and formed in a dense structure on the surface after anodic oxidation treatment. A fine granular cluster layer of hydroxyapatite and octacalcium phosphate were formed on the surface after the cyclic precalcification treatment. As a result of immersion test in the simulated body fluid (SBF), bioactivity was confirmed to be improved by the precipitation of protrusions appearing at the initial stage of formation of hydroxyapatite.

Objective: Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate. Methods: We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide. Results: The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively). Conclusion Policy on polypharmacy may influence psychiatrists’ decision-making. Thus, policies considering rational polypharmacy should be established.