Wheat AGAMOUS LIKE 6 transcription factors function in stamen development by regulating the expression of Ta APETALA3.

Previous studies have revealed the functions of rice and maize AGAMOUS LIKE 6 (AGL6) genes OsMADS6 and ZAG3, respectively, in floral development; however, the functions of three wheat (Triticum aestivum) AGL6 genes are still unclear. Here, we report the main functions of wheat AGL6 homoeologous genes in stamen development. In RNAi plants, stamens showed abnormality in number and morphology, and a tendency to transform into carpels. Consistently, the expression of the B-class gene TaAPETALA3 (AP3) and the auxin-responsive gene TaMGH3 was downregulated, whereas the wheat ortholog of the rice carpel identity gene DROOPING LEAF was ectopically expressed in RNAi stamens. TaAGL6 proteins bind to the promoter of TaAP3 directly. Yeast one-hybrid and transient expression assays further showed that TaAGL6 positively regulates the expression of TaAP3 in vivo. Wheat AGL6 transcription factors interact with TaAP3, TaAGAMOUS and TaMADS13. Our findings indicate that TaAGL6 transcription factors play an essential role in stamen development through transcriptional regulation of TaAP3 and other related genes. We propose a model to illustrate the function and probable mechanism of this regulation. This study extends our understanding of AGL6 genes.

Psychological symptoms of cancer survivors during the COVID-19 outbreak: A longitudinal study.

OBJECTIVE: Due to the coronavirus disease 2019 (COVID-19) pandemic, self-isolation at home was adopted to control the spread of COVID-19 in China for 3 months from 29 January 2020. The psychological status of cancer survivors is affected by their social environment. In this study, we investigated the psychological status and psychological symptoms of Chinese cancer survivors. METHODS: A longitudinal study design was adopted, and an online sample of cancer survivors was successfully recruited via the Internet communities of cancer support groups. From 14 February to 25 May, 111 cancer survivor families completed the symptom checklist 90 (SCL-90) online three times (T1:14 to 24 February; T2: 1 to 10 April; T3: 15 to 25 May). RESULTS: For survivors and their family members, the mean total score of the SCL-90 was 172.05 (13.30) and 142.76 (26.80) at T1, 155.91 (12.18) and 133.42 (15.93) at T2, and 142.75 (11.56) and 130.14 (14.16) at T3, respectively. The SCL-90 scores of cancer survivors were significantly higher than those of family members and Chinese norms at T1, T2, and T3. Nine psychological symptoms of the SCL-90 in cancer survivors significantly declined from T1 to T2 and T3. CONCLUSIONS: The COVID-19 pandemic has had a significant adverse impact on cancer survivors and their families. Psychological assistance should be provided to cancer survivors.

Supporting her as the situation changes: A qualitative study of spousal support strategies for patients with breast cancer in China.

OBJECTIVE: Spouses who are the major source of social support for married breast cancer patients sometimes do not know how to support the patient effectively. This study aimed to investigate the experiences and strategies of spouses identified as supportive for patients throughout the disease. METHODS: A qualitative study using semi-structured in-depth interviews was conducted with 22 husbands of Chinese women with breast cancer, who had effectively supported their wives. Thematic analysis was used for data analysis. RESULTS: Three themes emerged from the data: (a) following the diagnosis, the spouse focused on "problem solving under stress" by preparing the patient for the physician's disclosure of the diagnosis, helping her to cope with the shock, and aiding her in dealing with the treatment recommendations; (b) during treatment, the spouse focused on "functional compensation" to offset the patient's reduced self-care and family care abilities; and (c) following treatment, the spouse focused on "role return" by adapting to changes in the patient and assisting her return to the family and society. CONCLUSION: Chinese spouses of women with breast cancer exhibited support strategies that varied with disease progress. Healthcare providers should aid spouses in providing support according to the changing needs of patients with breast cancer.

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.

Breast Cancer Survivors Report Similar Concerns Related to Return to Work in Developed and Developing Nations.

Aim To determine whether breast cancer survivors (BCS) at work following the diagnosis and/or treatment of breast cancer, in a rapidly developing country such as China experience similar to return to work challenges as reported in nations with established return to work (RTW) policy and procedures for employees with cancer. Methods Semi-structured interviews were conducted with 16 BCS who returned to work following diagnosis and/or primary cancer treatment. An Interpretative Phenomenological Analysis was used to investigate responses. Results Three recurring themes emerged: (1) challenges at work related to residual effects of diagnosis and/or primary treatment; (2) positive and negative responses from employers and/or supervisors; and (3) positive and negative responses from co-workers/colleagues. Although several participants experienced a high level of workplace support, there was a subgroup that did report challenges related to symptom burden, cognitive limitations, and both positive and negative responses by employers and co-workers were reported. Conclusions Findings indicate similar challenges in BCS who RTW during and/or following cancer treatment in both rapidly developing and developed nations. Results suggest that regardless of the existence of workplace policies and practices related to RTW for workers with a history of cancer, a subgroup of BCS experience similar challenges when returning to work. These findings highlight the international nature of RTW challenges and suggest the need for more global efforts to develop and evaluate workplace interventions to assist with these similarities.

Experiences and insomnia-associated factors in Chinese breast cancer survivors: a qualitative study.

AIMS AND OBJECTIVES: This study aimed to explore the experiences and factors associated with insomnia in Chinese breast cancer survivors. BACKGROUND: Insomnia is a common and significant symptom in breast cancer survivors. Quantitative studies are unable to describe the experience of insomnia and the sleep-associated factors from a personal point of view. A profound understanding of the experience of insomnia in breast cancer survivors can provide information for health workers and caregivers to allow them to provide more effective support. DESIGN: A descriptive qualitative research was adopted. METHODS: In-depth interviews were conducted with 22 insomniac breast cancer survivors. A qualitative content analysis was used to analyse the data. RESULTS: Three themes emerged concerning the experiences of insomnia, including sleep neglect, insomnia perception and insomnia anxiety. Participants reported their own opinions on three insomnia-associated factors, including factors associated with hospitalisation, factors associated with breast cancer and the therapies and too much attention placed on sleep. CONCLUSIONS: Survivors would neglect their sleep problems in the early stage after diagnosis. When they became aware of their sleep problems, they were inclined to worry too much and sought help from traditional Chinese medicine. Anticipatory sleep anxiety, excessive negative cognitive activities and insomnia became a vicious circle for insomniac breast cancer survivors. RELEVANCE TO CLINICAL PRACTICE: The findings provide detailed information to help nurses understand the experiences of breast cancer survivors with insomnia. Nurses could provide proper care to help prevent insomnia or improve sleep.

[Flavanoids Extracted from Onion Inhibited Activation of Microglia and Release of Proinflammatory Factors around the Hematoma in ICH Model Rats].

OBJECTIVE: To study flavanoids extracted from onion (FEO) on the number of activated microglia and the release of proinflammatory factors in intracerebral hemorrhage (ICH) model rat at different time points, and to explore its possible mechanism for treating ICH. METHODS: Totally 100 Wistar rats were used for preparing ICH model, and ICH model was successfully established in 90 of them. The 90 rats were randomly divided into the sham-operation group (n =10) , the ICH group (n =40) , the FEO group (n =40). Totally 100 [L autoblood was injected from fixed position to rats in the ICH group and the FEO group during modeling. Meanwhile, FEO at 0. 2 mL/10 g was given to rats in the FEO group, twice daily. No drug intervention was given to rats in the ICH group and the sham-operation group. Each group was further sub-divided into 5 sub-groups according to different time points such as 6, 24, 48, 72 h, and 7 days. There were 8 rats in each sub-group of the ICH group and the FEO group, 10 groups in total. There were 2 rats in each subgroup of the sham-operation group, 5 groups in total. Neurological functions at different time points were observed by Garcia JH. The injury degree of brain tissue was observed at dif- ferent time points using HE staining. Activated microglia around hematoma were observed at different time points after ICH by using immunohistochemical staining. Expressions of TNF-α and IL-1 ß at different time points after ICH was detected using ELISA. RESULTS: In the ICH group, degenerated and necrotic zone occurred around hematoma after injecting autoblood, cells were untidily arranged with irregular nucleus, partial nucleus were shrunken with lamellar interstitial edema of the medulla. As time went by, degenerated and necrotic zone was dilated; vacant zone occurred around cells; cells were unevenly distributed with reduced neuron numbers. Meanwhile, infiltration of lymphocytes and neutrophils occurred. In the FEO group after FEO intervention, necrotic cells were lesser, cell arrangement and nucleus morphology were obviously alleviated, and infiltration of inflammatory cells was reduced at corresponding time points. Compared with the sham-operation group, behavioral scores at 5 time points all decreased, the number of activated microglia was added, and expressions of TNF-α and IL-1 ß in hematoma tissue increased in the ICH group (P <0. 01). Compared with the ICH group, behavioral scores at 48 and 72 h, as well as day 7 all increased, the number of activated microglia was reduced, and expressions of TNF-α and IL-1ß in hematoma tissue decreased in the FEO group (P <0. 01). CONCLUSION: FEO using the ethanol reflux method could improve symptoms of ICH model rats possibly by inhibiting activation of microolia and the release of proinflammatory factors around the hematoma.

Posttraumatic growth and psychological distress in Chinese early-stage breast cancer survivors: a longitudinal study.

OBJECTIVE: To describe the dynamic changes in posttraumatic growth (PTG) and psychological distress in hospitalized early-stage breast cancer (BC) survivors over a 6-month period. METHODS: A longitudinal study design was adopted. The PTG inventory (PTGI) and distress management screening measure were used 3 months after diagnosis, then again at 6 and 9 months after diagnosis. For baseline data, 155 BC patients who were receiving chemotherapy were selected from four first-class tertiary hospitals in Beijing from April 2010 to March 2011 using a purposive sampling method. Of these, 120 BC patients completed the follow-up investigation. A repeated measures analysis of variance, followed by least significant difference post-hoc analysis, was used to compare PTG and psychological distress. RESULTS: The total score of the PTGI was 62.72 ± 14.66 in BC survivors at 3 months after diagnosis.There was a weak negative relationship between PTG and psychological distress (r = ­0.282, p<0.001).PTG increased and psychological distress decreased from 3 to 9 months after diagnosis. The PTGI scores were 63.24 ± 14.21, 68.26 ± 15.29, and 70.29 ± 16.07 at 3, 6, and 9 months after diagnosis, respectively, with distress thermometer scores of 3.62 ± 1.98, 2.59 ± 2.00, and 2.51 ± 1.00, respectively. CONCLUSIONS: At 3 months after diagnosis, BC survivors develop PTG at a low level while they are receiving chemotherapy. PTG showed a weak negative association with psychological distress. The level of PTG shows an increasing tendency, whereas the degree of psychological distress exhibits a downward trend in the 9 months after diagnosis.

TP53R175H mutation promotes breast cancer cell proliferation through CORO1A-P38 MAPK pathway regulation.

Breast cancer is the most commonly diagnosed cancer in women. Among all types, triple-negative breast cancer is particularly challenging to cure because of its high recurrence rates and invasive and metastatic capacity. Although numerous studies have explored the role of TP53 mutations in cancer, there is a dearth of research regarding the correlation between TP53 mutations and breast cancer cell proliferation. In this study, our aim was to examine the impact of TP53 mutations on the prognosis of patients with breast cancer bioinformatics techniques. To detect cell proliferation, a CCK8 assay was performed, and western blotting was used to identify the expression of p53, p38, and p-p38 proteins. Cellular mRNA sequencing was used to screen target genes of TP53 mutations, and molecular docking was performed to identify the drugs that could hinder the proliferation of breast cancer cells.The results showed that the TP53 mutation rate is higher in patients with triple-negative breast cancer than non-triple-negative breast cancer, and those with TP53 mutations tended to have a poorer prognosis than those without. Patients with R175H site mutations also had shorter survival times than those without. Cytological experiments revealed that the TP53R175H mutation increases the rate of breast cancer cell proliferation. In conjunction with this, CORO1A was found to be a downstream target of TP53 mutations, and it was determined to promote breast cancer cell proliferation. Moreover, CORO1A overexpression resulted in the downregulation of p-p38 levels. Molecular docking studies further revealed that tea polyphenols can inhibit breast cancer proliferation by binding to p53.

Construction and validation of a risk-prediction model for chemotherapy-related cognitive impairment in patients with breast cancer.

PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.

Chronic Stress Dampens Lactobacillus Johnsonii-Mediated Tumor Suppression to Enhance Colorectal Cancer Progression.

Colorectal cancer development and outcome are impacted by modifiable risk factors, including psychologic stress. The gut microbiota has also been shown to be linked to psychologic factors. Here, we found a marked deteriorative effect of chronic stress in multiple colorectal cancer models, including chemically induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA sequencing data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed colorectal cancer group by activated ß-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on colorectal cancer progression. Stressed colorectal cancer mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC/MS-MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced colorectal cancer progression by decreasing ß-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on colorectal cancer. Altogether, these data identify that stress impacts the gut microbiome to support colorectal cancer progression. SIGNIFICANCE: Chronic stress stimulates cancer stemness by reducing the intestinal abundance of L. johnsonii and its metabolite PCA to enhance ß-catenin signaling, forming a basis for potential strategies to circumvent stress-induced cancer aggressiveness. See related commentary by McCollum and Shah, p. 645.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study.

PURPOSE: This study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. METHODS: The study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. RESULTS: The hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. CONCLUSION: Our findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients' cognitive decline throughout chemotherapy.

Right femoral vein and right dorsal artery thrombosis in childhood acute myeloid leukemia: A case report.

BACKGROUND: It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis. METHODS: We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency. RESULTS: After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered. CONCLUSION: For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.

TRPC absence induces pro-inflammatory macrophages and gut microbe disorder, sensitizing mice to colitis.

The transient receptor potential canonical (TRPC) channels, encoded in seven non-allelic genes, are important contributors to calcium fluxes, are strongly associated with various diseases. Here we explored the consequences of ablating all seven TRPCs in mice focusing on colitis. We discovered that absence of all seven TRPC proteins in mice (TRPC HeptaKO mice) promotes the development of dextran sulfate sodium (DSS)-induced colitis. RNA-sequence analysis highlighted an extremely pro-inflammatory profile in colons of DSS-treated TRPC HeptaKO mice, with an amount of increased pro-inflammatory cytokines and chemokines. Flow cytometry analysis showed that the infiltration of Ly6Chi monocytes and neutrophils in colonic lamina propria was significantly increased in DSS-treated TRPC HeptaKO mice. Results also revealed that macrophages from TRPC HeptaKO mice exhibited M1 polarization and enhanced secretion of pro-inflammatory factors. In addition, the composition of gut microbiota was markedly disturbed in DSS-treated TRPC HeptaKO mice. However, upon antibiotic cocktail (Abx)-treatment, TRPC HeptaKO mice showed no significant differences with WT mice in disease severity. Collectively, these data suggest that ablation of all TRPCs promotes the development of DSS-induced colitis by inducing pro-inflammatory macrophages and gut microbiota disorder.

Beta-adrenergic receptor blocker propranolol triggers anti-tumor immunity and enhances irinotecan therapy in mice colorectal cancer.

Colorectal cancer (CRC) stands as the second leading cause of cancer-related deaths worldwide with limited available medicines. While drug repurposing comes as a promising strategy for cancer treatment, we discovered that propranolol (Prop), a non-selective ß1 and ß2 adrenergic receptor blocker, significantly inhibited the development of subcutaneous CT26 CRC and AOM/DSS-induced CRC models. The RNA-seq analysis highlighted the activated immune pathways after Prop treatment, with KEGG analysis enriched in T-cell differentiation. Routine analyses of blood revealed a decrease in neutrophil to lymphocyte ratio, a biomarker of systemic inflammation, and a prognostic indicator in the Prop-treated groups in both CRC models. Analysis of the tumor-infiltrating immune cells exhibited that Prop regressed the exhaustion of CD4+ and CD8+ T cells in the CT26-derived graft models, which was further corroborated in the AOM/DSS-induced models. Furthermore, bioinformatic analysis fitted well with the experimental data, showing that ß2 adrenergic receptor (ADRB2) was positively correlated with T-cell exhaustion signature in various tumors. The in vitro experiment showed no direct effect of Prop on CT26 cell viability, while T cells were activated with significantly-upregulated production of IFN-γ and Granzyme B. Consistently, Prop was unable to restrain CT26 tumor growth in nude mice. At last, the combination of Prop and the chemotherapeutic drug Irinotecan acted out the strongest inhibition in CT26 tumor progress. Collectively, we repurpose Prop as a promising and economical therapeutic drug for CRC treatment and highlight T-cell as its target.

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study.

BACKGROUND: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) µg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). CONCLUSIONS: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00154180.

PEACE-S risk coping: A qualitative study exploring protective behavioral strategies of first-degree relatives of breast cancer survivors.

PURPOSE: Breast cancer is a major cause of morbidity worldwide and first-degree relatives of breast cancer survivors have a significantly higher risk of breast cancer that can be reduced by altering controllable risk factors. This study examined protective behavioral strategies used to cope with the risk in female first-degree relatives based on descriptions of their experiences, as well as their reason(s) for choosing a particular coping strategy. METHODS: A total of 25 first-degree relatives of breast cancer survivors in 13 families were recruited for this descriptive qualitative study. Data were collected between January and November 2020 through individual interviews, and a thematic analysis was performed using MAXQDA software. RESULTS: Three themes under an overarching theme of 'competition with breast cancer risk' were identified: (1) protective behavioral strategies for coping with breast cancer risk (four coping types); (2) barriers and facilitators for behavior change (five unfavorable and favorable factors related to the type of coping); and (3) significant determinants of coping strategy types. Based on these three themes, we developed a Personal restrictions, Exposure hazards, Adverse circumstances, Coping ability, Endorsement from social network, and Significant determinants ('PEACE-S') scale model of first-degree relatives' strategies for coping with breast cancer risk. CONCLUSIONS: First-degree relatives present different risk coping strategies that are shaped by individual and external factors and specific determinants. Our results provide insights that can help healthcare professionals design targeted interventions based on first-degree relatives' individual circumstances to mitigate breast cancer risk in this group through the adoption of healthy lifestyle choices.

Dysfunction of Cytotoxic T Lymphocyte Induced by Hepatoma Cells through the Gln-GLS2-Endoplasmic Reticulum Stress Pathway.

BACKGROUND: Metabolic activities of tumor cells lead to a depletion of nutrients within the tumor microenvironment, which results in the dysfunction of infiltrating T cells. Here, we explored how glutamine (gln) metabolism, which is essential for biosynthesis and cellular function, can affect the functions of cytotoxic T lymphocytes (CTLs). METHODS: Activated CTLs were co-cultured with hepatoma cells. Western blot was used to analyze changes of proteins and ELISA was used to analyze changes of effector. RNA-sequencing was used to detect differentially expressed genes in CTLs. The status of the endoplasmic reticulum (ER) was investigated using transmission electron microscopy experiments. RESULTS: Co-culturing CTLs and hepatoma cells revealed that CTLL-2 cells in the co-culture group expressed high levels of PD-1 (Programmed cell death protein 1), TIM-3 (T cell immunoglobulin and mucin domain-containing protein-3), GRP78 (Glucose regulated protein 78), and P-PERK (phosphorylated protein kinase RNA-activated-like endoplasmic reticulum kinase) and secreted low levels of Granzyme B and perforin. Additionally, the substructure of the ER was severely damaged. When CTLs were treated with an inhibitor of ER stress, their functions were restored. Next, complete medium without Gln was used to culture cells, causing CTLs to display dysfunction and ER stress. WB results revealed decreased expression levels of GLS2 and SLC1A5 (Solute carrier family 1 member 5) in CTLs in the co-culture group. Subsequently, glutaminase (GLS) inhibitors were added to the cultures. As expected, CTLs treated with a GLS2 inhibitor had increased protein content of PD-1 and TIM-3, decreased secretion of Granzyme B and perforin, and an enhanced ER stress response. CONCLUSIONS: In summary, CTLs are functionally downregulated induced by hepatoma cells through the Gln-GLS2-ERS pathway.

Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway.

Aims: In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function. Methods: The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP. Results: The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly. Conclusion: Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.