Restoration of corneal epithelial barrier function: A possible target for corneal neovascularization.

Corneal neovascularization (CoNV) is the second leading common cause of vision impairment worldwide and is a blinding pathological alteration brought on by ocular trauma, infection, and other factors. There are some limitations in the treatment of CoNV, hence it's critical to look into novel therapeutic targets. The corneal epithelial barrier, which is the initial barrier of the ocular surface, is an important structure that shields the eye from changes in the internal environment or invasion by the external environment. This study sought to collate evidence on the regulation of corneal epithelial barrier injury on the activation of vascular endothelial cells (VECs), basement membrane (BM) degradation, differentiation, migration, and proliferation of VECs, vascular maturation and stability, and other key processes in CoNV, so as to provide a novel concept for CoNV therapy targeting corneal epithelial barrier repair.

Fabrication of carboxymethyl cellulose-based thermo-sensitive hydrogels and inhibition of corneal neovascularization.

Corneal neovascularization (CNV) is a common multifactorial sequela of anterior corneal segment inflammation, which could lead to visual impairment and even blindness. The main treatments available are surgical sutures and invasive drug injections, which could cause serious ocular complications. To solve this problem, a thermo-sensitive drug-loaded hydrogel with high transparency was prepared in this study, which could achieve the sustained-release of drugs without affecting normal vision. In briefly, the thermo-sensitive hydrogel (PFNOCMC) was prepared from oxidized carboxymethyl cellulose (OCMC) and aminated poloxamer 407 (PF127-NH2). The results proved the PFNOCMC hydrogels possess high transparency, suitable gel temperature and time. In the CNV model, the PFNOCMC hydrogel loading bone morphogenetic protein 4 (BMP4) showed significant inhibition of CNV, this is due to the hydrogel allowed the drug to stay longer in the target area. The animal experiments on the ocular surface were carried out, which proved the hydrogel had excellent biocompatibility, and could realize the sustained-release of loaded drugs, and had a significant inhibitory effect on the neovascularization after ocular surface surgery. In conclusion, PFNOCMC hydrogels have great potential as sustained-release drug carriers in the biomedical field and provide a new minimally invasive option for the treatment of neovascular ocular diseases.

Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes.

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

BMP4 inhibits corneal neovascularization by interfering with tip cells in angiogenesis.

Corneal neovascularization (CNV) can lead to impaired corneal transparency, resulting in vision loss or blindness. The primary pathological mechanism underlying CNV is an imbalance between pro-angiogenic and anti-angiogenic factors, with inflammation playing a crucial role. Notably, a vascular endothelial growth factor（VEGF）-A gradient triggers the selection of single endothelial cells（ECs） into primary tip cells that guide sprouting, while a dynamic balance between tip and stalk cells maintains a specific ratio to promote CNV. Despite the central importance of tip-stalk cell selection and shuffling, the underlying mechanisms remain poorly understood. In this study, we examined the effects of bone morphogenetic protein 4 (BMP4) on VEGF-A-induced lumen formation in human umbilical vein endothelial cells (HUVECs) and CD34-stained tip cell formation. In vivo, BMP4 inhibited CNV caused by corneal sutures. This process was achieved by BMP4 decreasing the protein expression of VEGF-A and VEGFR2 in corneal tissue after corneal suture injury. By observing the ultrastructure of the cornea, BMP4 inhibited the sprouting of tip cells and brought forward the appearance of intussusception. Meanwhile, BMP4 attenuated the inflammatory response by inhibiting neutrophil extracellular traps （NETs）formation through the NADPH oxidase-2（NOX-2）pathway. Our results indicate that BMP4 inhibits the formation of tip cells by reducing the generation of NETs, disrupting the dynamic balance of tip and stalk cells and thereby inhibiting CNV, suggesting that BMP4 may be a potential therapeutic target for CNV.

Screening for adverse childhood experiences in antenatal care settings: A scoping review.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with many health problems in women during pregnancy, including depression/anxiety, gestational diabetes and adverse birth outcomes. However, unlike other health risk factors, screening for ACEs has not been widely implemented in antenatal care settings. AIMS: The aim of the scoping review was to explore the challenges in screening for ACEs in antenatal care settings and to provide the lessons learnt and evidence that guide the practice of ACE screening for both healthcare providers and pregnant women. METHODS: A five-stage process for conducting the scoping review was utilised. Searches of four key databases (PubMed, PsycINFO, CINAHL and SCOPUS) and reference lists from relevant studies were conducted. RESULTS: Seven publications met the inclusion criteria. Challenges identified for healthcare providers in screening for ACEs include lack of knowledge and confidence in ACE tool and shortage of time and resources to undertake screening. Impediments for pregnant women include concerns about privacy. However, there were examples of effective practice for ACE screening in antenatal care settings that could apply widely. CONCLUSION: Addressing impediments to ACE screening is critical in implementing trauma-informed practices that can identify women at risk of adverse health outcomes during pregnancy. A study on screening for ACEs in antenatal care in both public and private settings is needed to examine its feasibility and acceptability in the Australian context before being included in the National Perinatal Data Collection.

Life-Events Mediate the Prediction of Parental Alienation on Depression in Rural Left-Behind Children: A Longitudinal Study.

Objectives: Long-time separation with parents during early life, such as left-behind children (LBC, one or both of whose parents are leaving for work for at least a period of 6 months), may contribute to high alienation toward parents and endanger their mental health (e.g., depression). However, the dynamic status of depression and potential prediction of alienation on depression in LBC remained largely unknown. This study aimed to examine the dynamic status of depression, prediction of alienation toward parents on later depression in rural LBC, and a potential mediation of life-events. Methods: A total of 877 LBC in rural areas of China were recruited and surveyed at five time-points (baseline, T0: 1-month, T1: 3-months, T2: 6-months, T3: 12-months, T4) with the Inventory of Alienation Toward Parents, Childhood Depression Inventory, and Adolescent Self-Rating Life-Events Checklist. The Hierarchical Linear Model (HLM) and Hayes's PROCESS macro model were conducted to estimate the developmental trend and hierarchical predictors of depression. Results: The left-behind children aged 9-years old experienced higher depression than the children with other ages. At baseline, the children in the family atmosphere of frequent quarrels and compulsive parenting style reported a higher level of alienation toward parents, life-events, and depression. Alienation toward parents, life-events, and depression were positively and moderately correlated with each other (r = 0.14 ~ 0.64). The HLM model depicted a linear decline in depression, alienation, and life-events with an average rate of 0.23, 0.24, and 0.86, respectively, during the five time-points. Also, T0 alienation toward parents and T0 life-events positively predicted the developmental trajectory of depression over time, and T0 life-events positively predicted the descendant rate of depression. Notably, life-events mediated the prediction of baseline alienation toward parents on T4 depression in LBC. Conclusion: This study is among the first to reveal that alienation toward parents predicts the developmental trajectory of later depression in LBC. The findings that life-events mediate the prediction of alienation on later depression further suggest the importance of family and social factors in the occurrence of depression in LBC. The findings warrant the necessity to consider the family and social factors when evaluating and reducing risks for mental health problems in LBC, i.e., relationship with parents (especially alienation toward parents) and life-events need further attention.

The role of bone morphogenetic protein 4 in corneal injury repair.

PURPOSE: Corneal injury may cause neovascularization and lymphangiogenesis in cornea which have a detrimental effect to vision and even lead to blindness. Bone morphogenetic protein 4 (BMP4) regulates a variety of biological processes, which is closely relevant to the regulation of corneal epithelium and angiogenesis. Herein, we aimed to evaluate the effect of BMP4 on corneal neovascularization (CNV), corneal lymphangiogenesis (CL), corneal epithelial repair, and the role of BMP4/Smad pathway in these processes. METHODS: We used MTT assay to determine the optimal concentration of BMP4. The suture method was performed to induce rat CNV and CL. We used ink perfusion and HE staining to visualize the morphological change of CNV, and utilized RT-qPCR and ELISA to investigate the expression of angiogenic factors and lymphangiogenic factors. The effects of BMP4 and anti-VEGF antibody on migration, proliferation and adhesion of corneal epithelium were determined by scratch test, MTT assay and cell adhesion test. RESULTS: BMP4 significantly inhibited CNV and possibly CL. Topical BMP4 resulted in increased expression of endogenous BMP4, and decreased expression of angiogenic factors and lymphangiogenic factors. Compared with anti-VEGF antibody, BMP4 enhanced corneal epithelium migration, proliferation and adhesion, which facilitated corneal epithelial injury repair. Simultaneously, these processes could be regulated by BMP4/Smad pathway. CONCLUSIONS: Our results demonstrated unreported effects of BMP4 on CNV, CL, and corneal epithelial repair, suggesting that BMP4 may represent a potential therapeutic target in corneal injury repair.

Remote and adjacent psychological predictors of early-adulthood resilience: Role of early-life trauma, extraversion, life-events, depression, and social-support.

Resilience is important for people to maintain mental health after negative life-events. However, its longitudinal psychological and social predictors are poorly revealed. Based on the ecological system theory model, the current study aimed to determine the longitudinal temporal mechanism underlying the development of early-adulthood resilience using long-term (early-life trauma and personality), medium-term and short-term (life-events, social support, and depression) psychosocial predictors. A total of 505 university students were recruited at baseline (T1), 433 of whom took part in a three-year longitudinal investigation (T2). The results showed that at T1 and T2, the resilience scores of individuals were identically high (72.98 and 73.21, respectively). Pearson correlation analysis showed that early-adulthood resilience was negatively correlated with early-life trauma, psychoticism and neuroticism, depression, ad life-events, and positively correlated with extraversion, social-support, and resilience. Regression and structural equation models showed that extraversion had a direct positive effect on T1 resilience through the mediation of T1 life-events, depression, and social-support, while childhood emotional neglect (EN) had indirect negative effect and extraversion had direct positive effect on T2 resilience through the mediation of T1 resilience, and T2 depression and social-support. In conclusion, this study is among the first to reveal the longitudinal temporal process of the development of early-adulthood resilience using remote and adjacent psychosocial predictors. The findings confirm that childhood EN and extraversion have a remote impact on early-adulthood resilience through recent and current depression and social-support. Our results imply that early-life trauma does not hinder the development of early-adulthood resilience in a linear trend.

Fear in the Chinese Population: Influential Patterns in the Early Stage of the COVID-19 Pandemic.

Major global public health emergencies challenge public mental health. Negative emotions, and especially fear, may endanger social stability. To better cope with epidemics and pandemics, early emotional guidance should be provided based on an understanding of the status of public emotions in the given circumstances. From January 27 to February 11, 2020 (during which the cases of COVID-19 were increasing), a national online survey of the Chinese public was conducted. A total of 132,482 respondents completed a bespoke questionnaire, the Emotion Regulation Questionnaire, and the Berkeley Expressivity Questionnaire (BEQ). Results showed that at the early stage of the COVID-19 epidemic, 53.0% of the Chinese population reported varying degrees of fear, mostly mild. As seen from regression analysis, for individuals who were unmarried and with a relatively higher educational level, living in city or area with fewer confirmed cases, cognitive reappraisal, positive expressivity and negative inhibition were the protective factors of fear. For participants being of older age, female, a patient or medical staff member, risk perception, negative expressivity, positive impulse strength and negative impulse strength were the risk factors for fear. The levels of fear and avoidant behavior tendencies were risk factors for disturbed physical function. Structural equation modeling suggested that fear emotion had a mediation between risk perception and escape behavior and physical function disturbance. The findings help to reveal the public emotional status at the early stage of the pandemic based on a large Chinese sample, allowing targeting of the groups that most need emotional guidance under crisis. Findings also provide evidence of the need for psychological assistance in future major public health emergencies.

Negative Emotions in Chinese Frontline Medical Staff During the Early Stage of the COVID-19 Epidemic: Status, Trend, and Influential Pathways Based on a National Investigation.

Objective: The outbreak of coronavirus disease 2019 (COVID-19), declared as a major public health emergency, has had profound effects on public mental health especially emotional status. Due to professional requirements, medical staff are at a higher risk of infection, which might induce stronger negative emotions. This study aims to reveal the emotional status of Chinese frontline medical staff in the early epidemic period to better maintain their mental health, and provide adequate psychological support for them. Methods: A national online survey was carried out in China at the early stage of the COVID-19 epidemic. In total, 3025 Chinese frontline medical staff took part in this investigation which utilized a general information questionnaire, the Emotion Regulation Questionnaire (ERQ), and the Berkeley Expressivity Questionnaire (BEQ). Results: At the early stage of COVID-19, anxiety was the most common negative emotion of Chinese medical staff, followed by sadness, fear, and anger, mainly at a mild degree, which declined gradually over time. Nurses had the highest level of negative emotions compared with doctors and other healthcare workers. Women experienced more fear than men, younger and unmarried medical staff had more anxiety and fear compared with elders and married ones. Risk perception and emotional expressivity increased negative emotions, cognitive reappraisal reduced negative emotions, while negative emotions led to more avoidant behavior and more physical health disturbances, in which negative emotions mediated the effect of risk perception on avoidant behavior tendency in the model test. Conclusion: Chinese frontline medical staff experienced a mild level of negative emotions at the early stage of COVID-19, which decreased gradually over time. The findings suggest that during the epidemic, nurses' mental health should be extensively attended to, as well as women, younger, and unmarried medical staff. To better ensure their mental health, reducing risk perception and improving cognitive reappraisal might be important, which are potentially valuable to form targeted psychological interventions and emotional guidance under crisis in the future.

Regulation of bone morphogenetic protein 4 on epithelial tissue.

Epithelial tissues provide tissue barriers and specialize in organs and glands. When epithelial homeostasis is physiologically or pathologically stimulated, epithelial cells produce mesenchymal cells through the epithelial-mesenchymal transition, forming new tissues, promoting the cure of diseases or leading to illness. A variety of cytokines are involved in the regulation of epithelial cell differentiation. Bone morphogenetic proteins (BMPs), especially the bone morphogenetic protein 4 (BMP4) has a variety of biological functions and plays a prominent role in the regulation of epithelial cell differentiation. BMP4 is an important regulatory factor of a series of life activities in vertebrates, which is also related to cell proliferation, differentiation and mobility, it also has relation with tumor development. This paper mainly reviews the mechanism of BMP4's regulation on epithelial tissues, as well as its effect on the growth, differentiation, benign lesions and malignant lesions of epithelial tissues, and expounds the function of BMP4 in epithelial tissues, to provide theoretical support for the research on reducing epithelial diseases.