Effect of Adding Personalized Instant Messaging Apps to a Brief Smoking Cessation Model in Community Smokers in Hong Kong: Pragmatic Randomized Clinical Trial.

BACKGROUND: While text messaging has proven effective for smoking cessation (SC), engagement in the intervention remains suboptimal. OBJECTIVE: This study aims to evaluate whether using more interactive and adaptive instant messaging (IM) apps on smartphones, which enable personalization and chatting with SC advisors, can enhance SC outcomes beyond the provision of brief SC advice and active referral (AR) to SC services. METHODS: From December 2018 to November 2019, we proactively recruited 700 adult Chinese daily cigarette users in Hong Kong. Participants were randomized in a 1:1 ratio. At baseline, all participants received face-to-face brief advice on SC. Additionally, they were introduced to local SC services and assisted in selecting one. The intervention group received an additional 26 personalized regular messages and access to interactive chatting through IM apps for 3 months. The regular messages aimed to enhance self-efficacy, social support, and behavioral capacity for quitting, as well as to clarify outcome expectations related to cessation. We developed 3 sets of messages tailored to the planned quit date (within 30 days, 60 days, and undecided). Participants in the intervention group could initiate chatting with SC advisors on IM themselves or through prompts from regular messages or proactive inquiries from SC advisors. The control group received 26 SMS text messages focusing on general health. The primary outcomes were smoking abstinence validated by carbon monoxide levels of <4 parts per million at 6 and 12 months after the start of the intervention. RESULTS: Of the participants, 505/700 (72.1%) were male, and 450/648 (69.4%) were aged 40 or above. Planning to quit within 30 days was reported by 500/648 (77.2%) participants, with fewer intervention group members (124/332, 37.3%) reporting previous quit attempts compared with the control group (152/335, 45.4%; P=.04). At the 6- and 12-month follow-ups (with retention rates of 456/700, 65.1%, and 446/700, 63.7%, respectively), validated abstinence rates were comparable between the intervention (14/350, 4.0%, and 19/350, 5.4%) and control (11/350, 3.1% and 21/350, 6.0%) groups. Compared with the control group, the intervention group reported greater utilization of SC services at 12 months (RR 1.26, 95% CI 1.01-1.56). Within the intervention group, engaging in chat sessions with SC advisors predicted better validated abstinence at 6 months (RR 3.29, 95% CI 1.13-9.63) and any use of SC services (RR 1.66, 95% CI 1.14-2.43 at 6 months; RR 1.67, 95% CI 1.26-2.23 at 12 months). CONCLUSIONS: An IM-based intervention, providing support and assistance alongside brief SC advice and AR, did not yield further increases in quitting rates but did encourage the utilization of SC services. Future research could explore whether enhanced SC service utilization leads to improved long-term SC outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800719; https://clinicaltrials.gov/ct2/show/NCT03800719.

Life Satisfaction and Its Relationship With Personality Traits Among Medical College Students in China.

BACKGROUND: Life satisfaction is a comprehensive psychological index to measure a person's life quality. Previous studies have found that population sociological factors, physiological factors, psychological factors, and social factors all affect life satisfaction, but few studies have looked at the role of stable psychological factors, such as personality, in life satisfaction. Thus, this study combined previous research results and theories to study the current situation of college students' life satisfaction and its correlation with personality. OBJECTIVE: This study aims to comprehensively assess the life satisfaction levels among university students enrolled in a medical college in China, explore their correlation with various demographic factors and personality traits, identify potential areas for intervention, and provide recommendations for improving students' overall well-being and fostering the development of a positive and healthy personality. METHODS: A stratified cluster sampling method was used to select college students from a university. The questionnaire consists of general characteristics, a life satisfaction scale, and the Big Five Inventory. Descriptive statistical methods were conducted to describe the college students' life satisfaction status; an analysis of variance was performed to compare the score of life satisfaction among different demographic features; and the correlation between the score of life satisfaction and the Big Five Inventory was also analyzed. RESULTS: A total of 3116 subjects were included in this survey. The life satisfaction of females was higher than that of males in the dimensions of family, friends, school, and overall satisfaction (p<0.05). The life satisfaction of males in the self dimension was higher than that of females (p<0.05). The life satisfaction of different weight types had statistical significance in the life dimension (p<0.05). The life satisfaction of family, school, and overall well-being among smoking college students was lower than that of non-smoking college students (p<0.05). The life satisfaction of non-drinking college students in family, friends, life, school, and overall life satisfaction scores was higher than those of drinking college students (p<0.05). College students who get plenty of sleep a day (more than eight hours) scored higher life satisfaction scores in the self dimension than sleep-deprived college students (p<0.05). In addition to the family dimension, students taking long physical exercise breaks every day had higher life satisfaction scores in every dimension than students lacking physical exercise (p<0.05). The mean score of personality in the agreeableness and openness dimensions is the highest. Correlation analysis showed that the personality score in each dimension was positively correlated with the life satisfaction score in each dimension except for the neuroticism dimension of personality (p<0.05). CONCLUSION: The life satisfaction of college students is different for different lifestyles. The student management department should pay attention to the physical and mental health of college students with low life satisfaction and further find out the reasons for the difference in life satisfaction. Meanwhile, education should be strengthened for college students and encourage them to give up smoking and alcohol; strengthen physical training; and university education should strengthen the personality cultivation of college students.

Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells.

Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.

Association between tobacco industry denormalisation beliefs and support for tobacco endgame policies: a population-based study in Hong Kong.

OBJECTIVES: To examine the associations between tobacco industry denormalisation (TID) beliefs and support for tobacco endgame policies. METHODS: A total of 2810 randomly selected adult respondents of population-based tobacco policy-related surveys (2018-2019) were included. TID beliefs (agree vs disagree/unsure) were measured by seven items: tobacco manufacturers ignore health, induce addiction, hide harm, spread false information, lure smoking, interfere with tobacco control policies and should be responsible for health problems. Score of each item was summed up and dichotomised (median=5, >5 strong beliefs; ≤5 weak beliefs). Support for tobacco endgame policies on total bans of tobacco sales (yes/no) and use (yes/no) was reported. Associations between TID beliefs and tobacco endgame policies support across various smoking status were analysed, adjusting for sociodemographics. RESULTS: Fewer smokers (23.3%) had strong beliefs of TID than ex-smokers (48.4%) and never smokers (48.5%) (p<0.001). Support for total bans on tobacco sales (74.6%) and use (76.9%) was lower in smokers (33.3% and 35.3%) than ex-smokers (74.3% and 77.9%) and never smokers (76.0% and 78.3%) (all p values<0.001). An increase in the number of TID beliefs supported was positively associated with support for a total ban on sales (adjusted risk ratio 1.06, 95% CI 1.05 to 1.08, p<0.001) and use (1.06, 95% CI 1.05 to 1.07, p<0.001). The corresponding associations were stronger in smokers than non-smokers (sales: 1.87 vs 1.25, p value for interaction=0.03; use: 1.78 vs 1.21, p value for interaction=0.03). CONCLUSION: Stronger TID belief was associated with greater support for total bans on tobacco sales and use. TID intervention may increase support for tobacco endgame, especially in current smokers.

Microangiopathy associated with poor outcome of immunoglobulin A nephropathy: a cohort study and meta-analysis.

Background: Microangiopathy (MA) lesions are not rare in immunoglobulin A nephropathy (IgAN) and have been suggested to have a potential role in increasing risk in renal function decline. However, this suggestion has not been universally accepted. We aimed to investigate its role in our cohort and in multiple studies through a systematic meta-analysis. Methods: This cohort study included 450 IgAN patients, confirmed by renal biopsy, at Tongji Hospital, China, from January 2012 to December 2016. Clinical data were collected and analysed. We systematically searched PubMed and Web of Science for studies investigating the association between MA lesions and IgAN. Results: In our cohort, IgAN patients with MA were significantly older and had higher blood pressure, more proteinuria, worse kidney function and increased uric acid levels compared with patients without MA. When comparing pathological features with the non-MA group, the MA group exhibited more global glomerulosclerosis and interstitial fibrosis/tubular atrophy. MA lesions were independently associated with a composite kidney outcome in IgAN patients {adjusted hazard ratio 2.115 [95% confidence interval (CI) 1.035-4.320], P = .040}. Furthermore, this relationship was validated in a meta-analysis involving 2098 individuals from five independent cohorts. The combined data showed a 187% adjusted risk of poor renal outcome in IgAN patients with MA compared with patients without MA [adjusted risk ratio 2.87 (95% CI 2.05-4.02; I2 = 53%). Conclusion: MA lesions could serve as a valuable predictor for disease progression in patients with IgAN, extending beyond the widely recognized Oxford MEST-C score.

Focusing on the role of protein kinase mTOR in endometrial physiology and pathology: insights for therapeutic interventions.

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase crucial for cellular differentiation, proliferation, and autophagy. It shows a complex role in the endometrium, influencing both normal and pathogenic conditions. mTOR promotes the growth and maturation of endometrial cells, enhancing endometrial receptivity and decidualization. However, it also contributes to the development of endometriosis (EMs) and endometrial cancer (EC), thus emerging as a therapeutic target for these conditions. In this review, we summarize recent research progress on the mTOR signalling pathway in the endometrium. This provides insights into female endometrial structure and function and guides the prevention and treatment of related diseases.

Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies.

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Binocular Summation With Quantitative Contrast Sensitivity Function: A Novel Parameter to Evaluate Binocular Function in Intermittent Exotropia.

Purpose: Intermittent exotropia (IXT) is the most common form of strabismus. Surgery can potentially improve binocular function in patients with IXT. We aimed to evaluate binocular function using a novel parameter-binocular summation ratio (BSR), measured using quantitative contrast sensitivity function (CSF) in patients with IXT before and after surgery. Methods: Prospective study of 63 patients with IXT and 41 healthy controls were consecutively enrolled and underwent quantitative CSF testing binocularly and monocularly. BSR was calculated by dividing the CSF of the binocular value by the better monocular value. Forty-eight patients with IXT underwent strabismus surgery. BSR, stereoacuity, fusion ability, and strabismus questionnaires were assessed pre-operatively and 2 months postoperatively. Results: Sixty-three patients with IXT (median age = 9 years) compared with 41 healthy controls showed a worse mean BSR based on all CSF metrics at baseline (the area under the log CSF [AULCSF], spatial frequency [SF] cutoff, and contrast sensitivity at 1.0-18.0 cpd SF). All 48 patients with IXT showed successful alignment after surgery, and there were significant improvements in BSR based on the AULCSF, SF cutoff, and contrast sensitivity at 6.0, 12.0, and 18.0 cpd SF, respectively. The distance stereoacuity and fusion ability also improved after surgery, and a better BSR was associated with better stereoacuity and fusion. For strabismus questionnaires, the psychosocial subscale scores improved postoperatively, whereas the functional subscale scores did not change. Conclusions: BSR based on quantitative CSF can characterize binocular function across a range of spatial frequencies and can be used as a supplemental measurement for monitoring binocularity in patients with IXT in clinical settings.

Comparing the impact of three-dimensional digital visualization technology versus traditional microscopy on microsurgeons in microsurgery: a prospective self-controlled study.

BACKGROUND: Emerging three-dimensional digital visualization technology (DVT) provides more advantages than traditional microscopy in microsurgery; however, its impact on microsurgeons' visual and nervous systems and delicate microsurgery is still unclear, which hinders the wider implementation of DVT in digital visualization for microsurgery. METHODS AND MATERIAL: Forty-two microsurgeons from the Zhongshan Ophthalmic Center were enrolled in this prospective self-controlled study. Each microsurgeon consecutively performed 30 min conjunctival sutures using a three-dimensional digital display and a microscope, respectively. Visual function, autonomic nerve activity, and subjective symptoms were evaluated before and immediately after the operation. Visual functions, including accommodative lag, accommodative amplitude, near point of convergence and contrast sensitivity function (CSF), were measured by an expert optometrist. Heart rate variability was recorded by a wearable device for monitoring autonomic nervous activity. Subjective symptoms were evaluated by questionnaires. Microsurgical performance was assessed by the video-based Objective Structured Assessment of Technical Skill (OSATS) tool. RESULTS: Accommodative lag decreased from 0.63 (0.18) diopters (D) to 0.55 (0.16) D ( P =0.014), area under the log contrast sensitivity function increased from 1.49 (0.15) to 1.52 (0.14) ( P =0.037), and heart rate variability decreased from 36.00 (13.54) milliseconds (ms) to 32.26 (12.35) ms ( P =0.004) after using the DVT, but the changes showed no differences compared to traditional microscopy ( P >0.05). No statistical significance was observed for global OSATS scores between the two rounds of operations [mean difference, 0.05 (95% CI: -1.17 to 1.08) points; P =0.95]. Subjective symptoms were quite mild after using both techniques. CONCLUSIONS: The impact of DVT-based procedures on microsurgeons includes enhanced accommodation and sympathetic activity, but the changes and surgical performance are not significantly different from those of microscopy-based microsurgery. Our findings indicate that short-term use of DVT is reliable for microsurgery and the long-term effect of using DVT deserve more consideration.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

Prevalence and adverse outcomes of pre-operative frailty in patients undergoing carotid artery revascularization: a meta-analysis.

Introduction: Frailty can lead to a decrease in the patient's resistance to interference such as injury and disease, and cause a series of complications. An increasing number of studies have found that pre-operative frailty exacerbates the occurrence of adverse events after carotid artery revascularization, but an integrated quantitative analysis is currently lacking. Therefore, we conducted a meta-analysis to evaluate the impact of pre-operative frailty on patients undergoing carotid artery revascularization. Method: According to the PRISMA guidelines, we systematically searched for relevant studies on Medline, Embase, Ovid, CINAHL, Web Of Science, and Cochrane Library from establishment until June 2023. Summarize the risk of adverse outcome events through OR and 95% CI. Results: A total of 16 cohort studies were included, including 1692338 patients. Among patients who underwent carotid artery revascularization surgery, the prevalence of pre-operative frailty was 36% (95% CI = 0.18-0.53, P < 0.001). Compared with non frail individuals, frail individuals have an increased risk of mortality (OR = 2.35, 95% CI = 1.40-3.92, P = 0.001, I2 = 94%), stroke (OR = 1.33, 95% CI = 1.10-1.61, P = 0.003, I2 = 71%), myocardial infarction (OR = 1.86, 95% CI = 1.51-2.30, P < 0.001, I2 = 61%), and non-home discharge (OR = 2.39, 95% CI = 1.85-3.09, P < 0.001, I2 = 63%). Conclusion: The results of this article show that patients undergoing carotid artery revascularization have a higher prevalence of pre-operative frailty, which can lead to an increased risk of postoperative death, stroke, myocardial infarction, and non-home discharge. Strengthening the assessment and management of frailty is of great significance for patient prognosis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=416234, identifier: CRD42023416234.

Ultrasound findings of the sternoclavicular and shoulder joints in patients on maintenance hemodialysis.

INTRODUCTION: Ultrasonographic examination of joints is a non-invasive method to detect and monitor Dialysis-associated amyloidosis (DRA). METHODS: An ultrasonographic examination of the sternoclavicular (SC) and shoulder joints was performed in patients on maintenance hemodialysis (MHD) and those with normal renal function in the control group. The maximum distance (D) of SC, the rotator cuff thickness (RCs), and the echogenic pads (EPs) of the shoulder were evaluated. RESULTS: Compared with the control group, the MHD group had a higher D of SC, a higher proportion of RCs ≥8 mm, and a higher proportion of EPs positive. Adjust for age and Kt/V, the D of SC was positively related to dialysis vintage, standardized coefficients ß = 0.329, p = 0.004. A significant positive correlation existed between the D of SC and the RCs. CONCLUSION: In addition to the shoulder joint, the sternoclavicular is a suitable site for ultrasonographic detection of DRA.

Circulating small extracellular vesicles microRNAs plus CA-125 for treatment stratification in advanced ovarian cancer.

BACKGROUND: No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. METHODS: RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. RESULTS: Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). CONCLUSION: Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.

The prognostic significance of circulating plasma cells in newly diagnosed multiple myeloma patients.

Objective: Multiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM. Methods: This study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93). Results: Of the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs <0.165% had a PFS of <33 months (p=0.001). The median OS was not reached for two groups; the 3-year OS for patients with cPCs ≥0.165% was 71% compared with 87% for those with cPCs <0.165% (p=0.003). In transplant patients, cPCs ≥0.165% also predicted worse prognosis. Similarly, when considering cytogenetic risk factors in conjunction with cPC levels, comparable results were obtained. To evaluate whether the Revised International Staging System (R-ISS) groups could be further stratified based on different prognostic factors related to cPCs, our study revealed similar median PFS and OS rates in R-ISS II stage patients with cPCs ≥0.165% compared to those in the III stage (p=0.659 and 0.249, respectively). Conclusion: This study demonstrates that a high ratio of cPCs serves as a reliable indicator for predicting a poorer prognosis in MM cases. Furthermore, incorporating the R-ISS system and cytogenetic risk factors alongside the level of cPCs enhances the accuracy of prognostic predictions for patients with MM.

Translation of paired box 6 (PAX6) mRNA is IRES-mediated and inhibited by cymarin in breast cancer cells.

Paired box 6 (PAX6) is a member of the PAX family and plays an essential role in cancer cell cycle progression, colony formation, proliferation and invasion. Its expression is upregulated in many cancers including breast cancer, but the process of PAX6 mRNA translation has rarely been studied. We found that PAX6 translation level increased in MCF-7 breast cancer cells treated with the chemotherapeutic drug adriamycin (ADM), which might be attributable to internal ribosome entry site (IRES)-mediated translation. By modifying a bicistronic luciferase plasmid that is widely used to examine IRES activity, we found that the 469-base 5'-UTR of PAX6 mRNA contains an IRES element and that core IRES activity is located between nucleotides 159 and 333. Moreover, PAX6 IRES activity was induced during ADM treatment, which may be the main reason for the elevated level of PAX6 protein. We also found that cymarin, a cardiac glycoside, acts as an inhibitor of PAX6 protein expression by impairing its IRES-mediated translation. Furthermore, MCF-7 cell proliferation was suppressed during treatment with cymarin. These results provide novel insights into the translation mechanism of PAX6 in breast cancer cells and suggest that cymarin is a promising candidate for the treatment of breast cancer via targeting the expression of PAX6.

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases.

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

IL-2Rα-biased agonist enhances antitumor immunity by invigorating tumor-infiltrating CD25+CD8+ T cells.

To avoid regulatory T cell promotion and vascular toxicity, the interleukin-2 receptor-ß/interleukin-2 receptor-γ (IL-2Rßγ)-biased approach is used by most IL-2 analogs in immuno-oncology. However, recent clinical disappointments in these IL-2 agonists have questioned this strategy. Here we show that both wild-type (IL-2wt) and IL-2Rßγ-attenuated (IL-2α-bias) agonists that preserve IL-2Rα (CD25) activities can effectively expand tumor-specific CD8+ T cells (TSTs) and exhibit better antitumor efficacy and safety than the 'non-α' counterpart (IL-2nα). Mechanistically, TSTs coexpress elevated CD25 and PD-1 and are more susceptible to stimulation by IL-2Rα-proficient agonists. Moreover, the antitumor efficacy of anti-PD-1 depends on activation of PD-1+CD25+ TSTs through autocrine IL-2-CD25 signaling. In individuals with cancer, a low IL-2 signature correlates with non-responsiveness to anti-PD-1 treatment. In mouse models, IL-2α-bias, but not IL-2nα, restores the IL-2 signature and synergizes with anti-PD-1 to eradicate large established tumors. These findings underscore the indispensable function of CD25 in IL-2-based immunotherapy and provide rationales for evaluating IL-2Rα-biased agonists in individuals with cancer.

Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis.

OBJECTIVE: This study aimed to investigate the effect of oleracein E (OE) in improving 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC). METHODS: Lipopolysaccharide (LPS) was used to induce a UC cell model, and TNBS was used to induce a UC rat model. ELISA was performed to assess the levels of inflammatory factors (IL-1ß, TNF-α, and IL-6). Moreover, the activities of catalase (CAT), myeloperoxidase (MPO), and malonaldehyde (MDA) were detected by kits. Western blotting was performed to assess related proteins of the Nrf2/HO-1 signaling pathway, tight junction protein (ZO-1, Occludin, and claudin-2) expression levels, and apoptosis-related proteins (Bcl2, Bax, and cleaved caspase 3). Flow cytometry was used to analyze ROS levels. The morphology of colon tissues and the apoptosis of cells were detected by HE and TUNEL staining, respectively. RESULTS: OE significantly increased the activity of CAT and decreased the activity of MPO in LPS-induced Caco-2 cells and TNBS-induced UC rats. However, the levels of IL-1ß, IL-6, and TNF-α were markedly reduced both in vivo and in vitro. In addition, OE significantly increased the levels of Nrf2/HO-1 signaling pathway-related proteins and tight junction proteins and inhibited cell apoptosis. HE staining showed that OE significantly decreased the severity of acute TNBS-induced colitis in rats. CONCLUSION: OE may exert a regulatory effect on ameliorating intestinal barrier injury and reducing inflammation and oxidative stress levels by activating the Nrf2/HO-1 pathway.

Identification of angiogenesis-related genes signature for predicting survival and its regulatory network in glioblastoma.

Glioblastoma (GBM) is notorious for malignant neovascularization that contributes to undesirable outcome. However, its mechanisms remain unclear. This study aimed to identify prognostic angiogenesis-related genes and the potential regulatory mechanisms in GBM. RNA-sequencing data of 173 GBM patients were obtained from the Cancer Genome Atlas (TCGA) database for screening differentially expressed genes (DEGs), differentially transcription factors (DETFs), and reverse phase protein array (RPPA) chips. Differentially expressed genes from angiogenesis-related gene set were extracted for univariate Cox regression analysis to identify prognostic differentially expressed angiogenesis-related genes (PDEARGs). A risk predicting model was constructed based on 9 PDEARGs, namely MARK1, ITGA5, NMD3, HEY1, COL6A1, DKK3, SERPINA5, NRP1, PLK2, ANXA1, SLIT2, and PDPN. Glioblastoma patients were stratified into high-risk and low-risk groups according to their risk scores. GSEA and GSVA were applied to explore the possible underlying GBM angiogenesis-related pathways. CIBERSORT was employed to identify immune infiltrates in GBM. The Pearson's correlation analysis was performed to evaluate the correlations among DETFs, PDEARGs, immune cells/functions, RPPA chips, and pathways. A regulatory network centered by three PDEARGs (ANXA1, COL6A1, and PDPN) was constructed to show the potential regulatory mechanisms. External cohort of 95 GBM patients by immunohistochemistry (IHC) assay demonstrated that ANXA1, COL6A1, and PDPN were significantly upregulated in tumor tissues of high-risk GBM patients. Single-cell RNA sequencing also validated malignant cells expressed high levels of the ANXA1, COL6A1, PDPN, and key DETF (WWTR1). Our PDEARG-based risk prediction model and regulatory network identified prognostic biomarkers and provided valuable insight into future studies on angiogenesis in GBM.