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5 result(s) for "Pan, Po-Hung"
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Disruption of primary ciliary prostaglandin E2 signaling by transforming growth factor-β1 impairs endometrial receptivity
Background Infertility affects one in six individuals worldwide despite the advancement of assisted reproductive technologies. Successful embryo implantation is the first step of pregnancy, which relies on the establishment of a receptive uterine microenvironment. However, the mechanisms governing uterine receptivity and implantation failure remain incompletely characterized. Primary cilia serve as key cellular signaling hubs, yet their contribution to human decidualization and uterine receptivity remains largely unexplored. Methods Primary cultured human endometrial stromal cells (ESCs) were used to investigate the mechanisms of decidualization, functions of primary cilia, and effects of transforming growth factor-β (TGF-β) in inhibiting prostaglandin E 2 (PGE 2 )-induced decidualization. Human endometrial tissues (n = 108) were used to evaluate the clinicopathological parameters. The percentage of ciliated cells and cilia length were determined by immunofluorescent staining and AI-assisted quantification. Pseudopregnancy and pregnancy mouse models were employed to assess the effects of TGF-β1 on uterine receptivity and implantation outcomes. Results Prostaglandin E 2 , through binding to the EP4 receptor located at the primary cilium, stimulates ESC decidualization, which is augmented by 17β-estradiol and progesterone. Loss of ciliogenesis by genetic or pharmacological inhibition impairs decidualization. Proinflammatory cytokines such as TGF-β inhibit ciliogenesis and thus markedly attenuate PGE 2 -mediated decidualization. Mechanistically, TGF-β1 suppressed chicken ovalbumin upstream promoter transcription factor II and its downstream effector kinesin family member 3B, thereby inhibiting ciliogenesis and PGE₂-EP4 signaling. In mice, intrauterine administration of TGF-β1 impaired implantation, while TGF-β receptor blockade restored ciliogenesis, decidualization, and fertility. In women with endometriosis, ESCs displayed shortened cilia and reduced decidual response, which are due to elevated uterine and peritoneal TGF-β1-mediated suppression of ciliogenesis. Finally, women who failed to conceive after in vitro fertilization-embryo transfer (IVF-ET) have shorter and fewer primary cilia in ESCs. Receiver operating characteristic curve analysis demonstrated that both cilia length (AUC = 0.86) and ciliation frequency (AUC = 0.79) can serve as biomarkers for endometrial receptivity, providing predictive value for reproductive outcomes independent of ovarian reserve. Conclusions Endometrial primary cilia are indispensable for decidualization and are potential biomarkers for predicting endometrial receptivity. Targeting TGF-β signaling to restore ciliated cell number and ciliary length may serve as a potential therapeutic strategy to improve fertility outcomes.
Disruption of primary ciliary prostaglandin E 2 signaling by transforming growth factor-β1 impairs endometrial receptivity
Infertility affects one in six individuals worldwide despite the advancement of assisted reproductive technologies. Successful embryo implantation is the first step of pregnancy, which relies on the establishment of a receptive uterine microenvironment. However, the mechanisms governing uterine receptivity and implantation failure remain incompletely characterized. Primary cilia serve as key cellular signaling hubs, yet their contribution to human decidualization and uterine receptivity remains largely unexplored. Primary cultured human endometrial stromal cells (ESCs) were used to investigate the mechanisms of decidualization, functions of primary cilia, and effects of transforming growth factor-β (TGF-β) in inhibiting prostaglandin E (PGE )-induced decidualization. Human endometrial tissues (n = 108) were used to evaluate the clinicopathological parameters. The percentage of ciliated cells and cilia length were determined by immunofluorescent staining and AI-assisted quantification. Pseudopregnancy and pregnancy mouse models were employed to assess the effects of TGF-β1 on uterine receptivity and implantation outcomes. Prostaglandin E , through binding to the EP4 receptor located at the primary cilium, stimulates ESC decidualization, which is augmented by 17β-estradiol and progesterone. Loss of ciliogenesis by genetic or pharmacological inhibition impairs decidualization. Proinflammatory cytokines such as TGF-β inhibit ciliogenesis and thus markedly attenuate PGE -mediated decidualization. Mechanistically, TGF-β1 suppressed chicken ovalbumin upstream promoter transcription factor II and its downstream effector kinesin family member 3B, thereby inhibiting ciliogenesis and PGE₂-EP4 signaling. In mice, intrauterine administration of TGF-β1 impaired implantation, while TGF-β receptor blockade restored ciliogenesis, decidualization, and fertility. In women with endometriosis, ESCs displayed shortened cilia and reduced decidual response, which are due to elevated uterine and peritoneal TGF-β1-mediated suppression of ciliogenesis. Finally, women who failed to conceive after in vitro fertilization-embryo transfer (IVF-ET) have shorter and fewer primary cilia in ESCs. Receiver operating characteristic curve analysis demonstrated that both cilia length (AUC = 0.86) and ciliation frequency (AUC = 0.79) can serve as biomarkers for endometrial receptivity, providing predictive value for reproductive outcomes independent of ovarian reserve. Endometrial primary cilia are indispensable for decidualization and are potential biomarkers for predicting endometrial receptivity. Targeting TGF-β signaling to restore ciliated cell number and ciliary length may serve as a potential therapeutic strategy to improve fertility outcomes.
Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors
Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.
Respiratory health effects of the fiberglass-reinforced plastic lamination process in the yacht-building industry
Objectives Fiberglass-reinforced plastics (FRP) manufacturing has been related to cases of severe airway obstruction and elevated risk of respiratory mortality. But the specific job content risk is not clear. This study evaluated the respiratory health effects of the FRP lamination process. Methods A questionnaire was used to evaluate respiratory symptoms of workers in two yacht-building plants. Pre-shift (07:30-08:30 hours) and post-shift (17:00-18:00 hours) lung function was measured, while post-shift induced sputum was collected on the first day of the week. The participants were grouped into FRP laminators and non-laminators. Linear and logistic regression was used to investigate the effects of the lamination process on lung function. Results Laminators had a higher prevalence of chronic cough, lower pre-shift forced expiratory volume in first second (FEV1) and FEV1/force vital capacity (FVC) (-3.3% and -1.5%), lower post-shift FVC and FEV1 (-3.6% and -4.9%), and larger post-shift reduction of FVC (-2.1%) compared to non-laminators. The laminators also had higher risk of early obstructive and overall (obstructive plus restrictive) lung function impairment, and post-shift reduction of FVC >10% [odds ratio (OR) 5.98, 4.98, and 3.87, respectively). They also had higher percentages of neutrophils and lymphocytes in the induced sputum. Conclusion Laminators should undergo regular check-ups of respiratory symptoms and lung function. Further toxicologic studies are warranted to identify the specific causal agent in the FRP lamination process.
Design of Elliptic Reflective LED Surgical Shadowless Lamps Using Mathematical Optical Tracing Algorithms
Traditional surgical shadowless halogen lamps are generally designed as projection type with many light bulbs, which can produce not only mercury pollution but also heat radiation that are serious problems to patient. The study utilized Runge-Kutta methods and mathematical algorithms to design and optimize the freeform lens. The LED (light-emitting diode) was adopted to replace the traditional halogen lamp. A uniform lens was designed and fabricated based on the energy conservation. At first, the light field of LED is concentrated through the freeform lens to improve the optical efficiency. Second, the three-shell elliptic curves are applied to the reflective surgical shadowless lamps, where only few LED chips are needed. Light rays emitting from different directions to the target plane can achieve the goal of shadowless. In this study, the LED’s luminance flux is 1,895 lm. The shadow dilution on the target plane is 54%. Ec (central illuminance) is 114,900 lux, and the d50/d10 is 57% which is higher than the regulation by 7%, whereas the power consumption is only 20 W. The energy of reflective surgical shadowless lamps can save more than 50%, compared with the traditional projective one.