RESUMEN

Although extensive research has been conducted on the environmental impact of microplastics (MPs), their effects on microorganisms during the composting process and on the compost-soil system remain unclear. Our research investigates the microbial response to polylactic acid microplastics (PLAMPs) during aerobic composting and examines how compost enriched with PLAMPs affects plants. Our findings reveal that PLAMPs play a dual role in the composting process, influencing microorganisms differently depending on the composting phase. PLAMPs reduce the relative abundance of sensitive bacterial ASVs, specifically those belonging to Limnochordaceae and Enterobacteriaceae, during composting, while increasing the relative abundance of ASVs belonging to Steroidobacteriaceae and Bacillaceae. The impact of PLAMPs on microbial community assembly and niche width was found to be phase-dependent. In the stabilization phase (S5), the presence of PLAMPs caused a shift in the core microbial network from bacterial dominance to fungal dominance, accompanied by heightened microbial antagonism. Additionally, these intricate microbial interactions can be transferred to the soil ecosystem. Our study indicates that composting, as a method of managing PLAMPs, is also influenced by PLAMPs. This influence is transferred to the soil through the use of compost, resulting in severe oxidative stress in plants. Our research is pivotal for devising future strategies for PLAMPs management and predicting the subsequent changes in compost quality and environmental equilibrium.

RESUMEN

Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.

RESUMEN

BACKGROUND: It is well documented that childhood abuse increases the likelihood of emotional disorders particularly depressive symptoms. Childhood abuse might disrupt individuals' inhibitory control of emotional stimuli to increase the risk of depressive symptoms, and may differ in individuals' sensory processing sensitivity to the environment. OBJECTIVE: The current study aimed to examine the associations between childhood abuse and depressive symptoms among Chinese adolescents and test the mediating role of affective inhibitory control and the moderating role of sensory processing sensitivity in the relationship. METHODS: The childhood trauma questionnaire (CTQ), the highly sensitivity child scale (HSCS) and the center for epidemiological studies depression scale (CES-D) were administered to 234 junior school students who underwent the face-word Stroop task during which intraindividual reaction time variability (IIV) was calculated to assess affective inhibitory control. RESULTS: Childhood abuse was positively related to depressive symptoms. In addition, IIV under negative conditions partially mediated the relationship between childhood abuse and depressive symptoms. Sensory processing sensitivity moderated the mediation model, such that poor affective inhibitory control indexed by greater IIV under negative conditions was related to greater depressive symptoms in adolescents with high sensory processing sensitivity, but not in those with low sensory processing sensitivity. CONCLUSION: These findings suggest that disrupted affective inhibitory control of negative emotional stimuli serves as a potential mechanism linking childhood abuse with depressive symptoms, and is subjected to adolescent sensory processing sensitivity.

Asunto(s)

RESUMEN

MAIN CONCLUSION: Synthetic consortia performed better in promoting Schisandra chinensis growth than individual strains, and this result provides valuable information for the development of synthetic microbial fertilizers. Schisandra chinensis is an herbal medicine that can treat numerous diseases. However, the excessive reliance on chemical fertilizers during the plantation of S. chinensis has severely restricted the development of the S. chinensis planting industry. Plant growth-promoting rhizobacteria (PGPR) can promote the growth of a wide range of crops, and synthetic consortia of them are frequently superior to those of a single strain. In this study, we compared the effects of four PGPR and their synthetic consortia on S. chinensis growth. The pot experiment showed that compared with the control, synthetic consortia significantly increased the plant height, biomass, and total chlorophyll contents of S. chinensis, and their combined effects were better than those of individual strains. In addition, they improved the rhizosphere soil fertility (e.g., TC and TN contents) and enzyme activities (e.g., soil urease activity) and affected the composition and structure of soil microbial community significantly, including promoting the enrichment of beneficial microorganisms (e.g., Actinobacteria and Verrucomicrobiota) and increasing the relative abundance of Proteobacteria, a dominant bacterial phylum. They also enhanced the synergistic effect between the soil microorganisms. The correlation analysis between soil physicochemical properties and microbiome revealed that soil microorganisms participated in regulating soil fertility and promoting S. chinensis growth. This study may provide a theoretical basis for the development of synthetic microbial fertilizers for S. chinensis.

Asunto(s)

RESUMEN

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Asunto(s)

RESUMEN

BACKGROUND: Social interaction anxiety and sleep problems are prevalent during adolescence. Social interaction anxiety undermines sleep quality, however, little is known whether the association between social interaction anxiety and sleep quality is moderated by environmental factors such as childhood adversity and individual factors such as cardiac vagal control. This study sought to investigate the moderating effects of childhood adversity and cardiac vagal control on the link between social interaction anxiety and sleep quality. METHOD: The Social Interaction Anxiety Scale, the Pittsburgh Sleep Quality Index and the Childhood Trauma Questionnaire were administered to 274 adolescents, who received 3-min resting ECG recording to assess respiratory sinus arrhythmia (RSA) as an index of cardiac vagal control. RESULTS: Social interaction anxiety was negatively associated with sleep quality, and this association was moderated by childhood adversity and cardiac vagal control. In specific, social interaction anxiety was negatively associated with sleep quality among adolescents with low childhood adversity regardless of cardiac vagal control. Sleep quality was generally disrupted when adolescents exposed to high childhood adversity, but the negative association between social interaction anxiety and sleep quality among adolescents with high childhood adversity could be amortized by high cardiac vagal control. LIMITATIONS: Cross-sectional design precluded establishing causality among variables. CONCLUSION: These findings suggest that high cardiac vagal control reflecting better self-regulation might buffer the negative effect of social interaction anxiety on sleep quality particularly among adolescents exposed to early life stress.

Asunto(s)

RESUMEN

In order to investigate the 239+240Pu potential influence in the ocean, and develop a new method for rapidly monitoring radioactive pollution, the 239+240Pu spatial distribution in the South China Sea (SCS) and the Indian Ocean (IND) sediments is analyzed by SF-ICP-MS (ELEMENT 2). The inventory-weighted mean activities of 239+240Pu were 0.413 ± 0.333 mBq/g, 0.128 ± 0.044 mBq/g, and 0.483 ± 0.606 mBq/g in the sediments of the SCS, eastern IND, and Arabian Sea, respectively. The 239+240Pu activity spatial distribution in the SCS sediments was influenced by the current, the vertical distribution of Pu in seawater, and the transport of particulate matter. The 239+240Pu activity spatial distribution in the IND sediments could be impacted by Antarctic Intermediate Water. The average of 240Pu/239Pu atomic ratios were 0.258 ± 0.034, 0.219 ± 0.031, and 0.212 ± 0.028 in the sediments of the SCS, eastern IND, and Arabian Sea, respectively. The 240Pu/239Pu atomic ratios in the SCS and IND indicate that Pu from the Pacific Proving Ground (PPG) is transported to the IND via the SCS internal current and transverse ocean currents within Indonesia. In addition, a seawater advection-dispersion equation (S-ADE) model is established based on the actual physical processes of radionuclides in the seawater column and well fitting results were obtained (R2 = 0.49 to 0.99). The 239+240Pu data and the geographic information from the sample site were used to correct the Pu distribution in the seawater. The calculated 239+240Pu mean concentrations in the surface seawater were 2.465 mBq/m3 and 2.205 mBq/m3 for the SCS and the eastern IND seawater, respectively, and the result is consistent with the previous measurements. Then, the 239+240Pu stored in the study area of SCS and eastern IND was estimated to be approximately 1.0-1.4% of the global ocean based on the model. This study provides a useful model for guiding and designing future monitoring of pollution by anthropogenic Pu and other isotopes.

Asunto(s)

RESUMEN

Background: Life satisfaction (LS) serves as a crucial indicator of social wellbeing and plays a significant role in formulating strategies aimed at enhancing health outcomes among the hearing-disabled population. This study aimed to examine the effect of anxiety, depression, and structural social capital on life satisfaction among people with hearing disabilities in Shanghai, China. Methods: A cross-sectional study was conducted in Shanghai, China. As of March 2022, 337 people with hearing disabilities were recruited from the Shanghai Disabled Persons' Federation. An online survey was conducted using a four-part questionnaire to collect data including demographic characteristics, the Hospital Anxiety and Depression Scale (HADS), the Social Capital Scale (SCS), and a single-item question to measure life satisfaction. One-sample t-tests, Pearson's correlation analysis, and hierarchical multiple regression analysis were performed. Results: Anxiety (ß = - 0.153) and depression (ß = - 0.242) were significant factors influencing life satisfaction among people with hearing disabilities. Structural social capital also played an influential role in life satisfaction, and people with hearing disabilities who lack social networks (ß = 0.125) and social support (ß = 0.121) reported significantly lower levels of life satisfaction. However, no significant relationship was found in this study between LS and other components of structural social capital, such as social participation. Conclusion: This study shows that paying attention to mental health is critical for people with hearing disabilities to achieve social wellbeing and promote LS improvement. At the same time, the government and society also need to focus on the structural social capital, provide various social service programs, enhance social support, and expand social networks, improving LS for people with hearing disabilities.

RESUMEN

BACKGROUND: The aim of this study was to investigate the effect of citrulline on the pyroptosis of mouse macrophage RAW264.7 and the mechanism. We investigated the effect of citrulline on pyroptosis of RAW264.7 cell induced by lipopolysaccharide (LPS), and the modulation of nuclear factor-kappaB (NF-κB) signaling. METHODS: Pyroptosis was evaluated using flow cytometry and caspase-1/sytox double staining. Cell counting kit-8 assay was performed to evaluate cell viability. RESULTS: Citrulline promoted cell viability and inhibited the pyroptosis of RAW264.7 cell stimulated by LPS. Furthermore, citrulline inactivated NF-κb/p65 signaling pathway by suppressing p65 nuclear translocation induced by LPS. An NF-κb signaling pathway activator, betulinic acid, reversed the inhibition of pyroptosis induced by citrulline. CONCLUSION: Citrulline inhibited LPS-induced pyrophosis, which may be closely related to the inactivation of NF-κB/p65 signaling pathway.

Asunto(s)

RESUMEN

AIMS: Short-term blood pressure (BP) time in target range (TTR) independently predicts cardiovascular (CV) outcomes in adults. However, there are limited data regarding long-term TTR for BP among elderly participants. We aimed to determine whether future CV risk varies for those who can maintain a long-term systolic BP (SBP) target range by assessing TTR in elderly individuals with hypertension. METHODS AND RESULTS: The Chinese veteran cohort study included 943 elderly participants with hypertension aged over 75 years. The primary outcome was the first occurrence of CV events during annual visits. Time in target range was estimated over 15 years of follow-up using linear interpolation. The target range was defined as 120-140 mmHg according to guidelines. The association between SBP TTR and CV outcomes was estimated using multivariable Cox proportional hazards models. During the 15 year follow-up, the probability of CV events gradually decreased with increasing TTR for SBP. After multivariable adjustment for traditional CV risk factors and mean BP, comparing the highest vs. lowest quartiles of TTR for SBP, the hazard ratios (HRs) [95% confidence intervals (CIs)] were 0.424 (0.289-0.624) for the primary outcome. For each 1 SD increase in TTR, the risk of the primary outcome decreased by 25.4% (HR: 0.746; 95% CI: 0.666-0.834). Consistent findings were observed in sensitivity analyses. CONCLUSION: Greater long-term TTR for SBP was associated with a decreased risk of CV events in elderly individuals independent of mean BP, suggesting that SBP TTR might serve as a modifiable risk factor for future CV health in elderly patients with hypertension. LAY SUMMARY: This ongoing Chinese veteran cohort study adds to the understanding of the relationship between higher long-term systolic blood pressure (SBP) time in target range (TTR) and cardiovascular benefits among elderly individuals with hypertension.

Higher long-term systolic blood pressure (SBP) time in target range (TTR) is associated with a significantly decreased risk of cardiovascular events independent of mean SBP, suggesting that TTR might serve as an essential measure for monitoring BP status. It might be helpful for lowering the risk of cardiovascular events when the time in SBP target range is maintained after antihypertensive therapy.

Asunto(s)

RESUMEN

INTRODUCTION: Exposure to childhood trauma is found to increase internalizing and externalizing behavior problems in adolescents, however, the potential mechanism of this link remains underexplored. This study investigated the associations between childhood trauma and internalizing and externalizing behavior problems among adolescents, and tested the mediating role of executive function and the moderating role of life events stress in this relationship. METHODS: Questionnaire data were collected from 952 junior students in Northwest China. Participants ranged in age from 11 to 15 years old (M = 12.88 years, SD = 0.72; 53% females). SPSS 26.0 was used to analyze the relationship between variables and examine the mediation model and the moderated mediation model. RESULTS: Childhood trauma was positively associated with internalizing and externalizing behavior problems among adolescents. In addition, executive function partially mediated the relations between childhood trauma and internalizing and externalizing behavior problems. Life events stress was observed to moderate the relations between childhood trauma and executive function, as well as executive function and internalizing and externalizing behavior problems, but the effect sizes were relatively small. CONCLUSIONS: These findings underscore the role of executive function and life events stress in the association between childhood trauma and behavioral problems among adolescents.

Asunto(s)

RESUMEN

BACKGROUND: Sexual satisfaction is one of the issues faced by breast cancer survivors (BCSs). AIM: This study aims to explore the mediation of stigma in the relationship between perceived social support (PSS) and sexual satisfaction among breast cancer survivors. METHODS: A cross-sectional study was conducted among 918 BCSs in Shanghai Cancer Rehabilitation Club. Data were collected using an online questionnaire including questions on sociodemographic characteristics, health status, PSS, stigma and sexual satisfaction of participants. The bootstrap method was used to test the significance of the simple mediation model. OUTCOMES: The simple mediation of stigma was found significant in the relationship between PSS and sexual satisfaction. RESULTS: Stigma plays an intermediary role in the relationship between 2 dimensions of PSS (family and friends) and sexual satisfaction, but not in the relationship between the dimension of other significant people of PSS and sexual satisfaction. CLINICAL TRANSLATION: It is important to reduce stigma when improving the sexual satisfaction of BCSs from the perspective of PSS. STRENGTHS & LIMITATIONS: The mediating role of stigma in the relationship between PSS and sexual satisfaction among BCSs has been shown for the first time. Study limitations include limitations in the representativeness of population by the study sample and the cross-sectional study design. CONCLUSIONS: Stigma mediates the relationship between PSS and sexual satisfaction, which needs to be eliminated in intervention practice. Yuxin Zhang, Jie Zhao, Nan Jiang, et al. Effects of Stigma on the Relationship Between Perceived Social Support and Sexual Satisfaction Among Breast Cancer Survivors. J Sex Med 2022;19:1002-1011.

Asunto(s)

RESUMEN

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality, and so far patients have failed to benefit from therapeutics clinically available. Max interacting protein 1-0 (Mxi1-0) is one of the functional isoforms of Mxi1. Although it also binds to Max, Mxi1-0, unlike other Mxi1 isoforms, cannot antagonize the oncoprotein c-Myc because of its unique proline rich domain (PRD). While Mxi1-0 was reported to promote cell proliferation via largely uncharacterized mechanisms, it is unknown whether and how it plays a role in the pathogenesis of HPH. Methods: GEO database was used to screen for genes involved in HPH development, and the candidate players were validated through examination of gene expression in clinical HPH specimens. The effect of candidate gene knockdown or overexpression on cultured pulmonary arterial cells, e.g., pulmonary arterial smooth muscle cells (PASMCs), was then investigated. The signal pathway(s) underlying the regulatory role of the candidate gene in HPH pathogenesis was probed, and the outcome of targeting the aforementioned signaling was evaluated using an HPH rat model. Results: Mxi1 was significantly upregulated in the PASMCs of HPH patients. As the main effector isoform responding to hypoxia, Mxi1-0 functions in HPH to promote PASMCs proliferation. Mechanistically, Mxi1-0 improved the expression of the proto-oncogene c-Myc via activation of the MEK/ERK pathway. Consistently, both a MEK inhibitor, PD98059, and a c-Myc inhibitor, 10058F4, could counteract Mxi1-0-induced PASMCs proliferation. In addition, targeting the MEK/ERK signaling significantly suppressed the development of HPH in rats. Conclusion: Mxi1-0 potentiates HPH pathogenesis through MEK/ERK/c-Myc-mediated proliferation of PASMCs, suggesting its applicability in targeted treatment and prognostic assessment of clinical HPH.

RESUMEN

This study aimed to explore the molecular mechanism of myocardial protection. The effects of miR-32-3p and ring finger protein 13 (RNF13) on endoplasmic reticulum (ER) stress-induced apoptosis of A-10 cells and human umbilical vein endothelial cells (HUVEC) were detected using flow cytometry. The effects of miR-32-3p and phenylbutyric acid (PBA) on plaque instability and myocardial tissue injury in rats were investigated after establishment of arterial plaque model and embolization model and treatment with miR-32-3p-antagomir and PBA. RNF13, which was differentially expressed in myocardial infarction, was the direct target gene of miR-32-3p. MiR-32-3p inhibited RNF13 expression and targeted RNF13 to inhibit ER stress-induced cell apoptosis. Furthermore, inhibiting miR-32-3p expression induced arterial plaque instability by reducing survival, increasing pathological lesions in arterial tissue, up-regulating ER stress-related proteins, and regulating the expressions of apoptosis-related proteins in the model rats. However, PBA reversed the effects of miR-32-3p-antagomir on the model rats. MiR-32-3p regulates myocardial injury induced by micro-embolism and micro-vascular obstruction by targeting RNF13 to regulate the stability of atherosclerotic plaques.

Asunto(s)

RESUMEN

Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and pathways in VECs that are involved in the development and progression of unprovoked VTE (uVTE). The microarray dataset GSE118259 was downloaded from the Gene Expression Omnibus database, and 341 up-regulated and 8 down-regulated genes were identified in the VTE patients relative to the healthy controls, including CREB1, HIF1α, CBL, ILK, ESM1 and the ribosomal protein family genes. The protein-protein interaction (PPI) network and the transcription factor (TF)-miRNA-target gene network were constructed with these differentially expressed genes (DEGs), and visualized using Cytoscape software 3.6.1. Eighty-nine miRNAs were predicted as the targeting miRNAs of the DEGs, and 197 TFs were predicted as regulators of these miRNAs. In addition, 237 node genes and 4 modules were identified in the PPI network. The significantly enriched pathways included metabolic, cell adhesion, cell proliferation and cellular response to growth factor stimulus pathways. CREB1 was a differentially expressed TF in the TF-miRNA-target gene network, which regulated six miRNA-target gene pairs. The up-regulation of ESM1, HIF1α and CREB1 was confirmed at the mRNA and protein level in the plasma of uVTE patients. Taken together, ESM1, HIF1α and the CREB1-miRNA-target genes axis play potential mechanistic roles in uVTE development.

Asunto(s)

RESUMEN

OBJECTIVES: This study aims to explore the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. METHODS: A cross-sectional study was performed among 3996 Chinese cancer survivors recruited at Shanghai Cancer Rehabilitation Club from March to April 2017. Data were collected through self-reported questionnaires. The questionnaire includes information about demographic, cancer characteristics, comorbidities, lifestyle factors, and sexual satisfaction. Sexual satisfaction was measured by a single-item scale. The distribution of sexual satisfaction among different demographic and cancer characteristics was compared using the chi-squared test. Logistic regression models were conducted to assess the effects of lifestyle factors, comorbidities on sexual satisfaction after adjustment for demographic and cancer characteristics. RESULTS: More than 40% of male and female cancer survivors reported no sexual satisfaction. Sexual satisfaction of cancer survivors is significantly associated with both the number and the type of comorbidities. Heart disease, musculoskeletal system disease, diabetes, and hyperlipidemia are the comorbidities significantly associated with sexual satisfaction of cancer survivors. Lifestyle factors other than smoking, including exercise or fitness, drinking alcohol, and eating fruits and vegetables are significantly correlated with sexual satisfaction. Besides, all of the above associations show gender differences. In addition, demographic characteristics include sex, age, marital status, living status, and average monthly income are also significantly associated with sexual satisfaction of cancer survivors. CONCLUSION: Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction.

Asunto(s)

RESUMEN

OBJECTIVE: The folic acid analog pemetrexed (PMX) is recommended for the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, the mechanisms underlying PMX cytotoxicity in NSCLC remain to be fully explored. METHODS: PMX effect was evaluated in a urethane-induced lung adenocarcinoma mouse model. The interaction between PMX and intracellular proteins, particularly peroxisome proliferator-activated receptor γ (PPARγ), was investigated. The role of PPARγ in mediating pemetrexed cytotoxicity was investigated using NSCLC cell lines, mouse models and clinical specimens. RESULTS: This study found that PPARγ expression was correlated with prolonged progression-free survival in NSCLC patients. PPARγ downregulated hypoxanthine-guanine phosphoribosyl transferase (HGPRT), a key enzyme for nucleotide salvage synthesis, thereby sensitizing cells to PMX inhibition on nucleotide de novo synthesis. PMX was also a candidate partial agonist of PPARγ, and PMX-activated PPARγ bound to NF-κB and transcriptionally suppressed the NF-κB target gene, c-Myc. PMX inhibited tumor growth by activating PPARγ in a urethane-induced lung cancer model characterized by elevated NF-κB activity. CONCLUSION: PPARγ improves pemetrexed therapeutic efficacy in non-squamous NSCLC. The cytotoxicity effect of PMX can be synergized by activating PPARγ and thereby inhibiting NF-κB pathway.

RESUMEN

Vascular calcification (VC) accompanies the trans-differentiation of vascular smooth muscle cells (VSMCs) into osteo/chondrocyte-like cells and resembles physiological bone mineralization. However, the molecular mechanisms underlying VC initiation and progression have remained largely elusive. The aim of the present study was to identify the genes and pathways common to VSMC and osteoblast calcification and construct a regulatory network of non-coding RNAs and transcription factors (TFs). To this end, the Gene Expression Omnibus dataset GSE37558 including mRNA microarray data of calcifying VSMCs (CVSMCs) and calcifying osteoblasts (COs) was analyzed. The differentially expressed genes (DEGs) were screened and functionally annotated and the microRNA (miRNA/mRNA)-mRNA, TF-miRNA and long non-coding RNA (lncRNA)-TF regulatory networks were constructed. A total of 318 DEGs were identified in the CVSMCs relative to the non-calcified VSMCs, of which 43 were shared with the COs. The CVSMC-related DEGs were mainly enriched in the functional terms cell cycle, extracellular matrix (ECM), inflammation and chemotaxis-mediated signaling pathways, of which ECM was enriched by the DEGs for the COs as well. The protein-protein interaction network of CVSMCs consisted of 281 genes and 3,650 edges. There were 30 hub genes in this network, including maternal embryonic leucine zipper kinase (MELK), which potentially regulates the differentially expressed TF (DETF) forkhead box (FOX)M1 and is a potential target gene of Homo sapiens miR-485-3p and miR-181d. The TF-miRNA network included 251 TFs and 60 miRNAs, including 10 DETFs such as FOXO1 and snail family transcriptional repressor 2 (SNAI2). Furthermore, the lncRNAs H19 imprinted maternally expressed transcript (H19) and differentiation antagonizing non-protein coding RNA (DANCR) were predicted as the upstream regulators of FOXO1 and SNAI2 in the lncRNA-TF regulatory network. DANCR, MELK and FOXM1 were downregulated, and H19, FOXO1 and SNAI2 were upregulated in the CVSMCs. Taken together, the CVSMCs and COs exhibited similar molecular changes in the ECM. In addition, the MELK-FOXM1, H19/DANCR-FOXO1 and SNAI2 regulatory pathways likely mediate VSMC calcification.

RESUMEN

BACKGROUND: Breast cancer is a common tumor in China and has become a public health problem in modern society. Stress plays an important role in the occurrence and progression of cancer. At present, the current situation of stress on breast cancer survivors (BCSs) in China has not been fully understood. This study aims to explore the stress and coping strategies of Chinese BCSs, which provide suggestions to help BCSs reduce stress. METHODS: Sixty-three BCSs from the Shanghai Cancer Rehabilitation Club in China were included in this study and were divided into eight focus groups. These were transcribed verbatim, coded using thematic analysis and analyzed using NVivo 11. RESULTS: Three themes were extracted from the data to address our research objectives: stress, coping strategies and expectations. The stress of BCSs included psychological stress, stress caused by physical pain, economic stress, stress caused by the change of life status, and stress caused by information overload; the coping strategies included self-strategies and help from others; from the perspective of the survivors, they put forward their expectations for both the society and themselves. CONCLUSIONS: This study shows that BCSs face a variety of stress. In the face of stress, BCSs need comprehensive support, including social and family support to cope with stressors. The findings from this study provide evidence for improving the quality of life among BCSs.

Asunto(s)

RESUMEN

Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1ß (IL-1ß) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL-1ß or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH.

Asunto(s)