RESUMEN
OBJECTIVE: To explore whether thiotert treatment can inhibit proliferation and induce apoptosis in myelodysplastic syndromes (MDS) cells. METHODS: CCK-8 assay was used for determining the cytotoxicity of thiotert to MDS cell line SKM-1 and the reversal effect of GSH, NAC, and Z-VAD-FMK on thiotert-induced inhibition of cell viability. EdU assay was deployed to detect the cell proliferation ability. Intracellular reactive oxygen species (ROS) was measured by flow cytometry after DCFH-DA staining. The expression of DNA damage- and apoptosis-related proteins was detected by Western blot. RESULTS: Thiotert treatment significantly suppressed the cell viability and proliferation ability in SKM-1 cells. A large amount of ROS generation and markedly elevated C-PARP, C-Caspase 3, and γ-H2AX were observed after thiotert administration, while BCL-2 was significantly decreased. In addition, GSH, NAC, and Z-VAD-FMK were able to mitigate the cytotoxicity of thiotert on SKM-1 cells. CONCLUSION: Thiotert can promote MDS cell apoptosis by mediating ROS production and pro-apoptotic proteins expression.
Asunto(s)
Apoptosis , Proliferación Celular , Síndromes Mielodisplásicos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Apoptosis/efectos de los fármacos , Síndromes Mielodisplásicos/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Caspasa 3/metabolismo , Daño del ADN , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
PURPOSE: According to use and disuse theory, the decreasing size of families in China may have a considerable influence on older adults' health. However, research on the associations among family size, depression, and instrumental activities of daily living (IADL) in this population is limited. Thus, the current study examined the role of depression on the impact of family size on IADL and explored the differences between urban and rural areas. METHOD: Mediation analyses were performed with data from 7,290 older adults aged ≥60 years from the Harmonized China Health and Retirement Longitudinal Study in 2011, 2013, 2015, and 2018, using stepwise regression and bootstrap methods. RESULTS: Family size had a positive impact on IADL limitations of older adults (0.29, p < 0.01), and the masking effects of depressive symptoms had a partial effect of family size on older adults' IADL. However, these effects only exist in rural areas. CONCLUSION: Providing emotional support through psychological counseling and guiding caregivers to provide moderate care support is crucial, particularly in rural areas, for alleviating depressive symptoms due to changes in family size and maintaining independent living skills among older adults. [Research in Gerontological Nursing, 17(4), 165-175.].
Asunto(s)
Actividades Cotidianas , Depresión , Composición Familiar , Humanos , Actividades Cotidianas/psicología , Estudios Longitudinales , Femenino , Anciano , Masculino , Depresión/psicología , Depresión/epidemiología , China , Persona de Mediana Edad , Anciano de 80 o más Años , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricosRESUMEN
When solving mathematical problems, young children will perform better when they can use gestures that match mental representations. However, despite their increasing prevalence in educational settings, few studies have explored this effect in touchscreen-based interactions. Thus, we investigated the impact on young children's performance of dragging (where a continuous gesture is performed that is congruent with the change in number) and tapping (involving a discrete gesture that is incongruent) on a touchscreen device when engaged in a continuous number line estimation task. By examining differences in the set size and position of the number line estimation, we were also able to explore the boundary conditions for the superiority effect of congruent gestures. We used a 2 (Gesture Type: drag or tap) × 2 (Set Size: Set 0-10 or Set 0-20) × 2 (Position: left of midpoint or right of midpoint) mixed design. A total of 70 children aged 5 and 6 years (33 girls) were recruited and randomly assigned to either the Drag or Tap group. We found that the congruent gesture (drag) generally facilitated better performance with the touchscreen but with boundary conditions. When completing difficult estimations (right side in the large set size), the Drag group was more accurate, responded to the stimulus faster, and spent more time manipulating than the Tap group. These findings suggest that when children require explicit scaffolding, congruent touchscreen gestures help to release mental resources for strategic adjustments, decrease the difficulty of numerical estimation, and support constructing mental representations.
Asunto(s)
Gestos , Humanos , Femenino , Masculino , Preescolar , Niño , Solución de Problemas , Desempeño PsicomotorRESUMEN
Decline in cognitive function poses a substantial burden on individuals, families, and society. However, the longitudinal potential mechanism underlying the link of pain and cognitive function remains unclear. Using data of 4247 participants aged 60 years and over from the China Health and Retirement Longitudinal Study in 2011, 2013, 2018, and 2020, we discussed the longitudinal predictive effect of pain on cognitive function and the mediating effects of depressive symptoms and social participation. The longitudinal mediation model analysis revealed that pain could not directly influence cognitive function, but it could indirectly predict cognitive function through the independent mediation effects of depressive symptoms and social participation. Moreover, the association between pain and cognitive function was serially mediated by depressive symptoms and social participation. Diversified interventions aimed at relieving pain and depressive symptoms, and increasing social participation in older adults would be beneficial for their cognitive function.
Asunto(s)
Cognición , Depresión , Dolor , Participación Social , Humanos , Estudios Longitudinales , Masculino , Participación Social/psicología , Femenino , Anciano , Depresión/psicología , China , Dolor/psicología , Persona de Mediana Edad , Disfunción Cognitiva/psicología , Pueblos del Este de AsiaRESUMEN
Reactive oxygen species (ROS) serve as typical metabolic byproducts of aerobic life and play a pivotal role in redox reactions and signal transduction pathways. Contingent upon their concentration, ROS production not only initiates or stimulates tumorigenesis but also causes oxidative stress (OS) and triggers cellular apoptosis. Mounting literature supports the view that ROS are closely interwoven with the pathogenesis of a cluster of diseases, particularly those involving cell proliferation and differentiation, such as myelodysplastic syndromes (MDS) and chronic/acute myeloid leukemia (CML/AML). OS caused by excessive ROS at physiological levels is likely to affect the functions of hematopoietic stem cells, such as cell growth and self-renewal, which may contribute to defective hematopoiesis. We review herein the eminent role of ROS in the hematological niche and their profound influence on the progress of MDS. We also highlight that targeting ROS is a practical and reliable tactic for MDS therapy.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Síndromes Mielodisplásicos , Humanos , Especies Reactivas de Oxígeno , Estrés Oxidativo , Apoptosis , CarcinogénesisRESUMEN
With the panel data of 21 China's industrial industries from 2008 to 2020, the relationship models between intelligent industry, energy regulation and ecological transformation are constructed and tested from two dimensions of resource saving and environmental friendliness, then equity financing is introduced into this model as moderating variable to discuss the moderating effects on the relationships between intelligent industry, energy regulation and ecological transformation. Results show that: â´China's industrial industries significantly transformed to the resource-saving type, and the environment-friendly level stayed in a slow progression. âµIntelligent industry affected ecological transformation positively and significantly. The impact of energy regulation on ecological transformation was nonlinear. The regulation of energy consumption can significantly stimulate the transformation of resource saving, and restrain the transformation of environmental friendliness; the regulation of energy structure can significantly stimulate the transformation of environmental friendliness. ⶠEquity financing can positively moderate the relationship between intelligent industry and ecological transformation, and it can also moderate the regulation of energy structure and promote the transformation to environmental friendliness, especially in the low consumption industries.
Asunto(s)
Financiación del Capital , Industrias , China , Desarrollo EconómicoRESUMEN
BACKGROUND: Previous studies have suggested the dual sensory loss (DSL) is linked to depression, and that they are associated with higher healthcare expenditures, respectively. However, the association between DSL, depression and healthcare expenditures remains ambiguous. OBJECTIVES: The current study aims to examine the association between DSL, depression and healthcare expenditures as well as catastrophic health expenditures (CHE) among Chinese people aged 45 and above. METHODS: We first utilized the China Health and Retirement Longitudinal Survey (CHARLS) 2018 to obtain data from a total of 13,412 Chinese individuals aged 45 and above to conduct a cross-sectional study. DSL was defined as a combined variable of self-reported vision loss and hearing loss. Depression was measured using The Center for Epidemiologic Studies Depression Scale (CESD-10). The healthcare expenditures, including outpatient out-of-pocket cost and inpatient out-of-pocket cost, were obtained from the Harmonized CHARLS section. CHE were defined as out-of-pocket (OOP) health spending equal to or higher than 40 % of a household's capacity to pay. A Tobit linear regression with three models and a path analysis were conducted to estimate the association between DSL, depression and healthcare expenditures and CHE. Then we utilized 2011CHARLS and 2018CHARLS to present a longitudinal analysis. A path analysis was conducted to estimate the association between 2011DSL, 2018depression and 2018healthcare expenditures and CHE. RESULTS: Depression has a significant mediating effect between DSL and healthcare expenditures. (For outpatient OOP cost: a = 0.453, b = 23.559, c = 25.257, the proportion of mediating effect in total effect = 29.71 %; for inpatient OOP cost: a = 0.453, b = 13.606, c = 15.463, the proportion of mediating effect in total effect = 28.50 %; all P < 0.05). The mediating effect of depression also exists in the association between DSL and CHE (a = 0.453, b = 0.018, c = 0.043, the proportion of mediating effect in total effect = 15.90 %; P < 0.05). The mediation effect of depression on healthcare expenditures and CHE also exists in the longitudinal analysis using CHARLS 2011 and CHARLS 2018 (all P < 0.05). LIMITATIONS: The DSL status were based on self-report and we used 2018CHARLS to conduct the study, which may cause some bias. CONCLUSION: Significant mediating effect of depression exists between DSL and higher healthcare expenditures and CHE. The mental health of elder people with DSL should be focused on, and we should have an overall viewpoint on the topic of healthcare expenditures and CHE.
Asunto(s)
Depresión , Pueblos del Este de Asia , Gastos en Salud , Humanos , Enfermedad Catastrófica , Estudios Transversales , Depresión/epidemiologíaRESUMEN
Acute myeloid leukemia (AML) is a prevalent hematological malignancy that exhibits a wide array of molecular abnormalities. Although traditional treatment modalities such as chemotherapy and allogeneic stem cell transplantation (HSCT) have become standard therapeutic approaches, a considerable number of patients continue to face relapse and encounter a bleak prognosis. The emergence of immune escape, immunosuppression, minimal residual disease (MRD), and other contributing factors collectively contribute to this challenge. Recent research has increasingly highlighted the notable distinctions between AML tumor microenvironments and those of healthy individuals. In order to investigate the potential therapeutic mechanisms, this study examines the intricate transformations occurring between leukemic cells and their surrounding cells within the tumor microenvironment (TME) of AML. This review classifies immunotherapies into four distinct categories: cancer vaccines, immune checkpoint inhibitors (ICIs), antibody-based immunotherapies, and adoptive T-cell therapies. The results of numerous clinical trials strongly indicate that the identification of optimal combinations of novel agents, either in conjunction with each other or with chemotherapy, represents a crucial advancement in this field. In this review, we aim to explore the current and emerging immunotherapeutic methodologies applicable to AML patients, identify promising targets, and emphasize the crucial requirement to augment patient outcomes. The application of these strategies presents substantial therapeutic prospects within the realm of precision medicine for AML, encompassing the potential to ameliorate patient outcomes.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Inmunoterapia/métodos , Terapia de Inmunosupresión , Trasplante de Células Madre Hematopoyéticas/métodos , Microambiente TumoralRESUMEN
Background and Objectives: This study aims to explore the association between hearing impairment (HI) and functional disability and to examine whether depression mediates this association. Research Design and Methods: In the study, 11 335 individuals aged 45 years and older were analyzed from the China Health and Retirement Longitudinal Study. The study used logistic regression and Karlson/Holm/Breen's method to examine the correlation between HI, depression, and functional disability. Functional disability was assessed using activities of daily living and instrumental activities of daily living. Results: HI was significantly associated with activities of daily living disability (odds ratio [OR]â =â 1.34, 95% confidence interval [CI]â =â 1.21-1.49) and instrumental activities of daily living disability (ORâ =â 1.57, 95% CIâ =â 1.46-1.68). The mediated effect of depression accounted for 22.80% and 15.17% of the total effect of HI on activities of daily living and instrumental activities of daily living disability, respectively. Additionally, depression partially mediated the effects of HI on specific activities of daily living and instrumental activities of daily living tasks, including bathing (33.23%), toileting (27.50%), doing chores (37.36%), preparing meals (28.04%), shopping (25.81%), taking care of finances (11.82%), and taking medicine (12.71%). Discussion and Implications: HI increased the likelihood of functional disability partially through depression in middle-aged and older adults, suggesting that emphasizing the mental wellness of these people with HI is necessary to prevent impairments in physical function.
RESUMEN
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.
Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Ferroptosis , Daño por Reperfusión , Humanos , Anciano , Ferroptosis/fisiología , Especies Reactivas de Oxígeno/metabolismo , COVID-19/complicaciones , Enfermedades Cardiovasculares/etiología , SARS-CoV-2/metabolismo , Hierro/metabolismoRESUMEN
Objectives: Health workers in rural primary care systems are at increased risk of job burnout, but their associations with different positions have received scant attention in the literature. Thus, this study aims to measure job burnout in different positions in rural China and to identify factors associated with it. Methods: A cross-sectional survey was conducted with a total of 15,627 participants from six provinces in China. And job burnout was measured using the Chinese version of the Maslach Burnout Inventory-General Scale (MBI-GS). Multilevel regression analyses were used in examining factors potentially associated with job burnout in different positions. Results: Overall, more than half of providers suffered from moderate burnout. The degree of job burnout varied among different positions. Middle managers showed higher levels personal stress, while general staff showed the lowest interpersonal and self-evaluation dimensions of burnout. Job duty, job capability, job treatment, and career advancement are potential factors affecting these results. Conclusion: Interventions aimed at providing appropriate training and development opportunities, developing relevant career planning and management strategies, and implementing reasonable staffing and job design may be promising strategies for alleviating burnout in different positions and improving health system performance.
Asunto(s)
Agotamiento Psicológico , Personal de Salud , Humanos , Estudios Transversales , Ansiedad , China/epidemiologíaRESUMEN
BACKGROUND: With population aging becoming a pressing global concern, social support is more meaningful for older adults. In particular, financial supports, such as health insurance and financial assistance derived from family, all play great role in assistance affairs. Research shows social support possibly has an impact on poverty, but the association between formal and informal supports is unclear. We are aimed at verifying the association between distinct social supports and exploring whether this association would affect poverty alleviation for older adults. METHODS: A total of 2,683 individuals aged 60 years or older who have medical expenses were included in a survey conducted by the China Health and Retirement Longitudinal Study in 2018. A chi-square analysis and an independent samples T test all were used to explore the differences of social supports among old people with different economic condition. A binary logistic regression was aimed at analyzing the association between social supports and poverty for older adults. The structural equation model was established to evaluate the association between formal support and informal support and the mechanism(s) of social supports affecting poverty. RESULTS: The overall average rate of reimbursement for outpatient care was 0.20 with standard deviation 0.22, and the average reimbursement rate of inpatient care for the poor older adults is nearly 5% lower than the average of the non-poor older adults. We found that having private health insurance and higher reimbursement rate of inpatient care were associated with lower likelihood of living in poverty for older adults. Formal support would directly affect poverty, but its impact on poverty through informal support is insignificant even if formal support is negatively associated with informal support. CONCLUSION: A dilemma in reducing the economic burden of disease and receiving family assistance for older adults was revealed, and a more complete health security and higher level of medical expenses compensation would be beneficial to prevent poverty. Optimizing the primary healthcare and increasing the percentage of insurance compensation, policies that focus on the specific cultural values and strengthening the role of supplementary insurance are advantaged for alleviating poverty among older adults.
Asunto(s)
Pobreza , Jubilación , Humanos , Anciano , Estudios Longitudinales , China/epidemiología , Apoyo SocialRESUMEN
Objectives: This study aims to investigate the mediating role of depression and the moderating effect of gender in the relationship between total sleep time (TST) and instrumental activities of daily living (IADL) in middle-aged and elderly people (aged 45 or above). Methods: The data used in this study is from the China Health and Retirement Longitudinal Study (CHARLS), including a total of 10,460 respondents. Associations between TST, IADL, depression, and gender were analyzed using logistic regression and Karlson, Holm, and Breen (KHB) methods. Results: Short (OR = 1.42, 95% CI = 1.28-1.58 of ≤6 h) and long TST (OR = 1.16, 95% CI = 1.02-1.32 of 8-9 h; OR = 1.35, 95% CI = 1.19-1.54 of >9 h) were both associated with IADL. The mediation effect analyses observed that depression explained 64.80% of the total effect of short TST (≤6 h) and IADL, but was insignificant in long TST (8-9 h and >9 h). Meanwhile, gender has moderating effects on the mediation effect model. Conclusion: The study suggests that health interventions that focused on the dimensions of TST and depression are crucial for preventing functional disability while accounting for gender differences.
Asunto(s)
Actividades Cotidianas , Depresión , Anciano , Persona de Mediana Edad , Humanos , Depresión/epidemiología , Estudios Longitudinales , Duración del Sueño , China/epidemiologíaRESUMEN
Gastric cancer (GC) is one of the most common neoplastic malignancies, which permutes a fourth of cancer-related mortality globally. RNA modification plays a significant role in tumorigenesis, the underlying molecular mechanism of how different RNA modifications directly affect the tumor microenvironment (TME) in GC is unclear. Here, we profiled the genetic and transcriptional alterations of RNA modification genes (RMGs) in GC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through the unsupervised clustering algorithm, we identified three distinct RNA modification clusters and found that they participate in different biological pathways and starkly correlate with the clinicopathological characteristics, immune cell infiltration, and prognosis of GC patients. Subsequently, univariate Cox regression analysis unveiled 298 of 684 subtype-related differentially expressed genes (DEGs) are tightly interwoven to prognosis. In addition, we conducted the principal component analysis to develop the RM_Score system, which was used to quantify and predict the prognostic value of RNA modification in GC. Our analysis indicated that patients with high RM_Score were characterized by higher tumor mutational burden, mutation frequency, and microsatellite instability which were more susceptible to immunotherapy and had a favorable prognosis. Altogether, our study uncovered RNA modification signatures that may have a potential role in the TME and prediction of clinicopathological characteristics. Identification of these RNA modifications may provide a new understanding of immunotherapy strategies for gastric cancer.
RESUMEN
OBJECTIVES: This article aimed to examine the effects of social connection comprising loneliness and social isolation on cognitive impairment-free life expectancy (CIFLE). METHODS: Data on 28,563 older adults (aged 65+) were drawn from the Chinese Longitudinal Healthy Longevity Survey with a median follow-up of 4.00 years. Multistate Markov models were used to estimate the independent and joint effects of social connection with CIFLE. Cognitive impairment was measured by the modified Mini-Mental State Examination. RESULTS: For men and women, respectively, reduced CIFLEs at age 65 associated with loneliness were 0.95 (95% CI: 0.41-1.48) and 1.35 (95%: CI 0.77-1.90) years, and those associated with social isolation were 2.23 (95% CI: 1.67-2.78) and 2.49 (95% CI: 1.67-3.30) years. Compared with those with neither loneliness nor social isolation ('neither' group), older adults at age 65 with both loneliness and social isolation ('both group') lost CIFLEs of 2.68 (95% CI: 1.89-3.48) and 3.51 (95% CI, 2.55-4.47) years for men and women, respectively. Similar patterns were observed in the oldest-old adults (age 85 or over). A growth trend transpired in the difference of the proportion of the remaining CIFLE between 'neither' group and 'both' group with age. CONCLUSION: Loneliness and social isolation are associated with decreased CIFLE in older Chinese adults. Policy makers and the public must be informed that early identification and management of loneliness and social isolation, especially when coexisting, are crucial.
Asunto(s)
Disfunción Cognitiva , Soledad , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Soledad/psicología , Aislamiento Social/psicología , Disfunción Cognitiva/psicología , Estudios Longitudinales , Esperanza de VidaRESUMEN
BACKGROUND: Studies have shown chronic disease-based healthcare utilization inequity is common. Hence, exploring this issue can help in establishing targeted measures and protecting the rights and interests of vulnerable groups. Against this background, the purpose of this study is to explore the latent classification of elderly patients with chronic disease and compare healthcare utilization inequity among latent classes. METHODS: This study used the data of 7243 elderly patient with chronic diseases collected from the China Health and Retirement Longitudinal Study in 2018. Latent class analysis was used to classify the patients with chronic diseases, and analysis of variance and [Formula: see text] tests were utilized to test the differences in characteristics among latent classes. Healthcare utilization inequity was measured based on the concentration index (CI), and the CI was decomposed to compare the horizontal index of healthcare utilization among the latent classes. RESULTS: The patients with chronic diseases were divided into five latent classes, namely, the musculoskeletal system, hypertension, respiratory system, digestive system and cardiovascular system groups. Statistically significant differences in social demographic characteristics were observed among the five latent classes (P < 0.05). A pro-rich healthcare utilization inequity for all respondents was observed (outpatient CI = 0.080, inpatient CI = 0.135), and a similar phenomenon in latent classes was found except for the musculoskeletal system group in outpatient visits (CI = -0.037). The digestive system group had the worst equity (outpatient CI = 0.197, inpatient CI = 0.157) and the respiratory system group had the best (outpatient CI = 0.001, inpatient CI = 0.086). After balancing the influence of health need factors, healthcare utilization inequity was almost alleviated. Furthermore, for all respondents, the contribution of health need factors (65.227% for outpatient and 81.593% for inpatient) was larger than that of socioeconomic factors (-21.774% for outpatient and 23.707 for inpatient), and self-rated health status was the greatest contributor (57.167% for outpatient and 79.399% for inpatient). The characteristics were shown in latent classes. CONCLUSIONS: Healthcare utilization inequity still exists in elderly patients with chronic diseases, and the specific performances of inequity vary among latent classes. Moreover, self-rated health status plays an important role in healthcare utilization inequity. Providing financial support to low-income patients with certain chronic diseases, focusing on their physical and mental feelings and guiding them to evaluate their health status correctly could be essential for alleviating healthcare utilization inequity among elderly patients with chronic diseases.
Asunto(s)
Disparidades en Atención de Salud , Aceptación de la Atención de Salud , Humanos , Anciano , Estudios Longitudinales , Factores Socioeconómicos , China/epidemiología , Enfermedad CrónicaRESUMEN
Background: Gastric cancer (GC) is an important disease and the fifth most common malignancy worldwide. Autophagy is an important process for the turnover of intracellular substances. Autophagy-related genes (ARGs) are crucial in cancer. Accumulating evidence indicates the clinicopathological significance of the tumor microenvironment (TME) in predicting prognosis and treatment efficacy. Methods: Clinical and gene expression data of GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A total of 22 genes with differences in expression and prognosis were screened from 232 ARGs. Three autophagy patterns were identified using an unsupervised clustering algorithm and scored using principal component analysis to predict the value of autophagy in the prognosis of GC patients. Finally, the relationship between autophagy and ferroptosis was validated in gastric cancer cells. Results: The expression of ARGs showed obvious heterogeneity in GC patients. Three autophagy patterns were identified and used to predict the overall survival of GC patients. These three patterns were well-matched with the immunophenotype. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses showed that the biological functions of the three autophagy patterns were different. A scoring system was then set up to quantify the autophagy model and further evaluate the response of the patients to the immunotherapy. Patients with high autophagy scores had a more severe tumor mutation burden and better prognosis. High autophagy scores were accompanied by high microsatellite instability. Patients with high autophagy scores had significantly higher PD-L1 expression and increased survival. The experimental results confirmed that the expression of ferroptosis genes was positively correlated with the expression of autophagy genes in different autophagy clusters, and inhibition of autophagy dramatically reversed the decrease in ferroptotic cell death and lipid accumulation. Conclusions: Autophagy patterns are involved in TME diversity and complexity. Autophagy score can be used as an independent prognostic biomarker in GC patients and to predict the effect of immunotherapy and ferroptosis-based therapy. This might benefit individualized treatment for GC.
RESUMEN
Breast invasive carcinoma (BRCA) is a carcinoma with a fairly high incidence, and the therapeutic schedules are generally surgery and chemotherapy. However, chemotherapeutic drugs tend to produce serious toxic side effects, which lead to the cessation of treatment. Therefore, it is imperative to develop treatment strategies that are more effective and have fewer side effects at the genetic level. Centromeric protein W (CENPW) is an oncogene that plays an important part in nucleosome assembly. To date, no studies have reported the prognostic significance of CENPW in breast carcinoma. In this study, we verified that CENPW expression is up-regulated in breast carcinoma and positively associated with the level of immune cell infiltration. The clinicopathological characteristics further suggest that CENPW expression is correlated with a worse prognosis of breast carcinoma. Interestingly, the CENPW mutation contributes to the poor prognosis. Next, we discovered that the genes interacting with CENPW are mainly concentrated in the cell cycle pathway, and CENPW is co-expressed with CDCA7, which is also highly expressed in breast carcinoma and leads to a worse prognosis. Our subsequent studies verified that knockdown of CENPW significantly inhibits the proliferation and migration of breast carcinoma cells and promotes their apoptosis rate. Notably, inhibition of CEMPW sensitizes breast cancer cells to chemotherapeutic drugs that have been found to induce cell cycle arrest. In summary, these results provide extensive data and experimental evidence that CENPW can serve as a novel predictor of breast cancer and may act as a prospective therapeutic target.
RESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas, with high mortality and poor prognoses worldwide. Succinate dehydrogenase (SDH) consists of four nuclear-encoded subunits and it is the only complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Previous studies have shown decreased SDH activity in ccRCC. However, the role and underlying molecular mechanisms of SDH in ccRCC initiation and development remain unclear. In the present study, pan-cancer analysis of SDH gene expression was analyzed and the relationship between SDH gene expression and clinicopathological parameters was assessed using different databases. cBioPortal, UACLAN, and Tumor Immune Estimation Resource (TIMER) were subsequently utilized to analyze genetic alterations, methylation, and immune cell infiltration of SDH genes in ccRCC patients. We found SDHs were significantly downregulated in ccRCC tissues and correlated with ccRCC progression. Increased methylation and high SDH promoter mutation rates may be the cause of reduced expression of SDHs in ccRCC. Moreover, the interaction network showed that SDH genes were correlated with ferroptosis-related genes. We further demonstrated that SDH inhibition dampened oxidative phosphorylation, reduced ferroptotic events, and restored ferroptotic cell death, characterized by eliminated mitochondrial ROS levels, decreased cellular ROS and diminished peroxide accumulation. Collectively, this study provides new insights into the regulatory role of SDH in the carcinogenesis and progression of ccRCC, introducing a potential target for advanced antitumor therapy through ferroptosis.
Asunto(s)
Carcinoma de Células Renales , Ferroptosis , Neoplasias Renales , Carcinogénesis/genética , Carcinoma de Células Renales/metabolismo , Femenino , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismoRESUMEN
Camellia oleifera is believed to exhibit a complex intraspecific polyploidy phenomenon. Abnormal microsporogenesis can promote the formation of unreduced gametes in plants and lead to sexual polyploidy, so it is hypothesized that improper meiosis probably results in the formation of natural polyploidy in Camellia oleifera. In this study, based on the cytological observation of meiosis in pollen mother cells (PMCs), we found natural 2n pollen for the first time in Camellia oleifera, which may lead to the formation of natural polyploids by sexual polyploidization. Additionally, abnormal cytological behaviour during meiosis, including univalent chromosomes, extraequatorial chromosomes, early segregation, laggard chromosomes, chromosome stickiness, asynchronous meiosis and deviant cytokinesis (monad, dyads, triads), was observed, which could be the cause of 2n pollen formation. Moreover, we confirmed a relationship among the length-width ratio of flower buds, stylet length and microsporogenesis. This result suggested that we can immediately determine the microsporogenesis stages by phenotypic characteristics, which may be applicable to breeding advanced germplasm in Camellia oleifera. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01002-5.