Association between stigma and quality of life among chronic refractory wounds patients and informal caregivers: an actor-partner interdependence model analysis.

PURPOSE: The co-occurrence of health impairments in patients and their informal caregivers may be particularly common in intimate care settings in China. Patients with Chronic Refractory Wounds (CRWs) and their informal caregivers constitute a dyad and exhibit dyadic effects during the caring process. Unfortunately, no study has yet explored the dyadic effects of stigma on the QoL of patients with CRWs and their caregivers. METHODS: We used a convenience sampling method and recruited CRWs patient-caregiver dyads (N = 207) in China between April 2022 and October 2023. RESULTS: We found that: (i) dyadic members experience varying degrees of stigma; (ii) the actor-partner effect of CRWs patients' stigma on their own and their informal caregivers' QoL was significant (Path A1: ß = - 1.27, Path A2: ß = - 0.37, Path P1: ß = - 0.08, Path P2: ß = - 0.18); (iii) informal caregivers' stigma adversely affects both their own and their patients' psychological QoL((Path A4: ß = - 0.65, Path P4: ß = - 0.52)). Informal caregivers' stigma can negatively impact patients' physical QoL (Path P3: ß = - 0.17), whereas it does not significantly affect their own physical QoL. CONCLUSION: There is a notable actor-partner effect of the CRWs patients' stigma on their own and their informal caregivers' QoL. CRWs patients' stigma should become a priority for the government to improve CRWs patients' and informal caregivers' QoL. Besides, health professionals should be addressing several assessments and interventions to decrease informal caregivers' affiliate stigma symptoms and improve CRWs patients' and informal caregivers' QoL.

YM155 inhibits retinal pigment epithelium cell survival through EGFR/MAPK signaling pathway.

AIM: To investigate YM155's effect on retinal pigment epithelium (RPE) cells' viability and the potential regulatory mechanisms. METHODS: Human immortalized RPE cell lines (ARPE-19 cell line) were processed with YM155 and epidermal growth factor (EGF). ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay, and apoptosis was tested by flow cytometry assay. ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay, and migration ability was evaluated via a wound-healing assay. Epidermal growth factor receptor (EGFR)/MAPK pathway proteins were tested via immunoblotting. EGFR localization was examined by immunofluorescence assay. RESULTS: YM155 suppressed ARPE-19 cells' viability in a time and concentration-dependent manner. A high dose of YM155 caused a small amount of ARPE-19 cell death. YM155 significantly diminished the ARPE-19 cells' proliferative and migrative capacity. YM155 down-regulated total EGFR and phosphorylated external signal-regulated protein kinase (ERK), and it up-regulated the phosphorylation of P38MAPK and c-Jun N-terminal kinase (JNK). YM155 induced endocytosis of EGFR in ARPE-19 cell. YM155 also attenuated EGF-induced ARPE-19 cells' proliferative and migrative capacity. Moreover, YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF. CONCLUSION: YM155 inhibits RPE cell survival, the cell proliferative and migrative capacity, and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway. YM155 might, therefore, be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.

Inhibiting endoplasmic reticulum stress by activation of G-protein-coupled estrogen receptor to protect retinal astrocytes under hyperoxia.

Retinal vascularization is arrested at the early (hyperoxia) stage in retinopathy of prematurity (ROP), a leading cause of blindness in children. Estrogen was reported to alleviate ROP by inhibiting reactive oxygen species, the upstream signaling molecules of endoplasmic reticulum stress (ERS). Astrocytes have long been proposed to guide angiogenesis, because they form a reticular network that provides a substrate for migrating endothelial cells. However, the factors that control the vascularization of the immature retina and the therapeutic mechanism of estrogen in early ROP remain poorly understood. This study aimed to investigate the role of G-protein-coupled estrogen receptor (GPER), an estrogen receptor distributed in the endoplasmic reticulum (ER), in protecting retinal astrocytes under hyperoxia and the association with ERS. The results showed that GPER was widely expressed in retinal astrocytes. GPER activation increases cell viability, decreases apoptosis, and autophagy of retinal astrocytes, decreases inositol-1,4,5-triphosphate receptor activity, and increases Ca2+ concentration in ER of astrocytes under hyperoxia. GPER blockade reversed all of these changes. Together, our findings indicate that GPER can protect the survival of retinal astrocytes by inhibiting ERS under hyperoxia.

G-protein-coupled estrogen receptor protects retinal ganglion cells via inhibiting endoplasmic reticulum stress under hyperoxia.

Abnormal development of immature retinal vascular structure in preterm infants under the condition of hyperoxia is the primary cause of retinopathy of prematurity (ROP), which has become the leading cause of blindness in children. Retinal ganglion cells (RGCs) play a critical role in the normal growth of retinal vessels. Previous studies have indicated that estrogen can alleviate retinal lesions in the ROP animal model by inhibiting reactive oxygen species, which is associated with endoplasmic reticulum (ER) stress. This study aimed to investigate the protecting effect of G-protein coupled estrogen receptor (GPER), one of the estrogen receptors distributed in ER, on RGCs in the early stage of ROP and its relationship with ER stress. We found that GPER was widely expressed in primary cultured murine RGCs. GPER activation by its agonist G-1 increased cell vitality and decreased apoptosis and autophagy of RGCs under hyperoxia. GPER activation by G-1 decreased the expressions of the ER stress proteins, including inositol-requiring kinase/endonuclease 1α, pancreatic ER stress kinase, and cleaved activating transcription factor 6 in ER of RGCs under hyperoxia. GPER activation decreased IP3R activity and increased Ca2+  concentration in ER of RGCs under hyperoxia. In addition, GPER antagonist (G-15) reversed all these effects of the GPER agonist mentioned above. This study suggested that GPER activation can protect the survival of RGCs in the early stage of ROP via reducing ER stress in RGCs under the condition of hyperoxia.

G-protein coupled estrogen receptor activation protects the viability of hyperoxia-treated primary murine retinal microglia by reducing ER stress.

In this study, we investigated the effects of G-protein coupled estrogen receptor (GPER) activation in the early phase of retinopathy of prematurity (ROP) and its association with endoplasmic reticulum (ER) stress using primary murine retinal microglia as an experimental model. Fluorescence microscopy results show that the CD11c-positive primary retinal microglia in vitro cultured for 14 days were GPER-positive. GPER activation using GPER-agonist G-1 reduced autophagy and increased the viability of the hyperoxia-treated primary murine retinal microglia. Furthermore, GPER activation reduced the expression of ER stress-related proteins, IRE1α, PERK and ATF6 in the hyperoxia-treated primary murine retinal microglia compared to the corresponding controls. GPER activation significantly reduced a time-dependent increase in IP3R-dependent calcium release from the ER, thereby maintaining higher calcium levels in the ER of hyperoxia-treated primary retinal microglia. However, the protective effects of G-1 on the hyperoxia-treated primary retinal microglia were eliminated by inactivation of GPER using the GPER-antagonist, G-15. In conclusion, our study demonstrates that GPER activation enhances the survival of hyperoxia-treated primary retinal microglia by reducing ER stress. Our study demonstrates the therapeutic potential of GPER agonists such as G-1 in the early phase of ROP.