Comparison of Female Ovarian Reserve Before vs After COVID-19 Vaccination.

This cohort study examines the association of COVID-19 vaccination with levels of anti-Mullerian hormone and antral follicle count in women seeking fertility treatment.

Children's cross-cultural categorizations of racially ambiguous faces in Taiwan and the U.S.

OBJECTIVES: Racially ambiguous face categorization research is growing in prominence, and yet the majority of this work has focused on White and Western samples and has primarily used biracial Black/White stimuli. Past findings suggest that biracial Black/White faces are more often seen as Black than White, but without testing these perceptions with other groups, generalizability cannot be guaranteed. METHODS: We tested 3-7-year-old Asian children living in Taiwan-an Eastern cultural context (N = 74)-and Asian children living in the U.S.-a Western cultural context (N = 65) to explore the role that cultural group membership may play in biracial perceptions. Children categorized 12 racially ambiguous biracial Black/White faces and 12 biracial Asian/White faces in a dichotomous forced-choice task and completed a racial constancy measurement. RESULTS: Regarding biracial Black/White faces, Taiwanese and Asian American children both categorized the faces as White significantly more often compared to chance levels, regardless of racial constancy beliefs. For biracial Asian/White faces, Taiwanese children with racial constancy beliefs categorized the faces significantly more often as White, whereas Taiwanese children without racial constancy beliefs categorized the faces significantly more often as Asian. However, Asian American children did not show a bias in categorizing biracial Asian/White faces. CONCLUSIONS: Results suggest that hyperdescent over hypodescent for more commonly studied biracial Black/White faces generalizes in both cultural contexts. However, biracial Asian/White stimuli may be perceived in more fixed-like patterns in predominately Asian contexts, since only Taiwanese children showed increased outgroup categorizations once racial constancy beliefs were endorsed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Complement-mediated release of fibroblast growth factor 2 from human RPE cells.

PURPOSE: Complement activation is associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Fibroblast growth factor 2 (FGF2) and membrane attack complex (MAC) are present in eyes of patients with CNV. Herein, we investigated the effect of complement activation on FGF2 release in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with an anti-RPE antibody and then treated with C1q-depleted human serum in the presence or absence of Tec kinases inhibitor (LFM-A13). 38 cytokines/chemokines levels were measured by Luminex technology. Secretion of FGF2 and interleukin (IL)-6 was assessed by ELISA. Tec protein was measured by Western blot. mRNA expression of FGF2, chemokine (C-X-C motif) ligand 1 (CXCL-1), and family members of Tec kinases was evaluated by qPCR. Cell viability and MAC deposition were determined by WST-1 assay and flow cytometry, respectively. RESULTS: Complement activation caused increased FGF2 and IL-6 release. FGF2 was released when C6-depleted human serum was reconstituted with C6. Anti-C5 antibody significantly attenuated complement-mediated FGF2 release, but not IL-6. FGF2 mRNA levels were not affected, while CXCL-1 mRNA levels were increased by complement activation. FGF2-containing extracellular vesicles were detected in response to complement challenge. Tec mRNA and protein were expressed in RPE cells. In the presence of LFM-A13, secretion of FGF2, but not IL-6, and MAC deposition were significantly decreased and cell viability was significantly increased in complement-treated cells when compared to controls. CONCLUSIONS: Complement plays an important role to release FGF2 from RPE cells. Tec kinase is involved in MAC formation and complement-mediated FGF2 release. This information suggests a role for complement activation to mediate neovascularization in conditions such as AMD, and may elucidate potential therapeutic targets.

Risuteganib Protects against Hydroquinone-induced Injury in Human RPE Cells.

Purpose: Cigarette smoking has been implicated in the pathogenesis of AMD. Integrin dysfunctions have been associated with AMD. Herein, we investigate the effect of risuteganib (RSG), an integrin regulator, on RPE cell injury induced by hydroquinone (HQ), an important oxidant in cigarette smoke. Methods: Cultured human RPE cells were treated with HQ in the presence or absence of RSG. Cell death, mitochondrial respiration, reactive oxygen species production, and mitochondrial membrane potential were measured by flow cytometry, XFe24 analyzer, and fluorescence plate reader, respectively. Whole transcriptome analysis and gene expression were analyzed by Illumina RNA sequencing and quantitative PCR, respectively. F-actin aggregation was visualized with phalloidin. Levels of heme oxygenase-1, P38, and heat shock protein 27 proteins were measured by Western blot. Results: HQ induced necrosis and apoptosis, decreased mitochondrial bioenergetics, increased reactive oxygen species levels, decreased mitochondrial membrane potential, increased F-actin aggregates, and induced phosphorylation of P38 and heat shock protein 27. HQ, but not RSG alone, induced substantial transcriptome changes that were regulated by RSG cotreatment. RSG cotreatment significantly protected against HQ-induced necrosis and apoptosis, prevented HQ-reduced mitochondrial bioenergetics, decreased HQ-induced reactive oxygen species production, improved HQ-disrupted mitochondrial membrane potential, reduced F-actin aggregates, decreased phosphorylation of P38 and heat shock protein 27, and further upregulated HQ-induced heme oxygenase-1 protein levels. Conclusions: RSG has no detectable adverse effects on healthy RPE cells, whereas RSG cotreatment protects against HQ-induced injury, mitochondrial dysfunction, and actin reorganization, suggesting a potential role for RSG therapy to treat retinal diseases such as AMD.

Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in Retinal Pigment Epithelial Cells.

Purpose: Oxidative stress in retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD). Resveratrol exerts a range of protective biologic effects, but its mechanism(s) are not well understood. The aim of this study was to investigate how resveratrol could affect biologic pathways in oxidatively stressed RPE cells. Methods: Cultured human RPE cells were treated with hydroquinone (HQ) in the presence or absence of resveratrol. Cell viability was determined with WST-1 reagent and trypan blue exclusion. Mitochondrial function was measured with the XFe24 Extracellular Flux Analyzer. Expression of heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit was evaluated by qPCR. Endoplasmic reticulum stress protein expression was measured by Western blot. Potential reactions between HQ and resveratrol were investigated using high-performance liquid chromatography mass spectrometry with resveratrol and additional oxidants for comparison. Results: RPE cells treated with the combination of resveratrol and HQ had significantly increased cell viability and improved mitochondrial function when compared with HQ-treated cells alone. Resveratrol in combination with HQ significantly upregulated HO-1 mRNA expression above that of HQ-treated cells alone. Resveratrol in combination with HQ upregulated C/EBP homologous protein and spliced X-box binding protein 1. Additionally, new compounds were formed from resveratrol and HQ coincubation. Conclusions: Resveratrol can ameliorate HQ-induced toxicity in RPE cells through improved mitochondrial bioenergetics, upregulated antioxidant genes, stimulated unfolded protein response, and direct oxidant interaction. This study provides insight into pathways through which resveratrol can protect RPE cells from oxidative damage, a factor thought to contribute to AMD pathogenesis.

Neutrophil elastase enhances antigen presentation by upregulating human leukocyte antigen class I expression on tumor cells.

Neutrophil elastase (NE) is an innate immune cell-derived inflammatory mediator that we have shown increases the presentation of tumor-associated peptide antigens in breast cancer. In this study, we extend these observations to show that NE uptake has a broad effect on enhancing antigen presentation by breast cancer cells. We show that NE increases human leukocyte antigen (HLA) class I expression on the surface of breast cancer cells in a concentration and time-dependent manner. HLA class I upregulation requires internalization of enzymatically active NE. Western blots of NE-treated breast cancer cells confirm that the expression of total HLA class I as well as the antigen-processing machinery proteins TAP1, LMP2, and calnexin does not change following NE treatment. This suggests that NE does not increase the efficiency of antigen processing; rather, it mediates the upregulation of HLA class I by stabilizing and reducing membrane recycling of HLA class I molecules. Furthermore, the effects of NE extend beyond breast cancer since the uptake of NE by EBV-LCL increases the presentation of HLA class I-restricted viral peptides, as shown by their increased sensitivity to lysis by EBV-specific CD8+ T cells. Together, our results show that NE uptake increases the responsiveness of breast cancer cells to adaptive immunity by broad upregulation of membrane HLA class I and support the conclusion that the innate inflammatory mediator NE enhances tumor cell recognition and increases tumor sensitivity to the host adaptive immune response.