The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

Dietary Antioxidant Insufficiency Is Associated With Increased Inflammatory Markers and Poorer Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Antioxidant insufficiency, elevated inflammatory markers, and poor health-related quality of life (HRQOL) are prevalent in patients with heart failure (HF). OBJECTIVE: The objective of this study was to examine the associations among dietary antioxidant intake, inflammatory markers, and HRQOL in patients with HF. METHODS: This was a secondary analysis of 265 patients with HF who completed a 4-day food diary. We assessed intake of 10 antioxidants: alpha carotene, beta carotene, beta cryptoxanthin, lutein, zeaxanthin, lycopene, vitamins C and E, zinc, and selenium. Antioxidant insufficiency was reflected by a measured level for each antioxidant that was below the estimate average requirement or lower than median for antioxidants without an estimate average requirement. Inflammatory markers including serum C-reactive protein, cytokines (interleukins 6 and 10), tumor necrosis factor-alpha, and soluble receptors (sTNFR1 and sTNFR2) were assessed with enzyme immunoassay. Health-related quality of life was measured using the Minnesota Living with Heart Failure at 12 months. RESULTS: Dietary antioxidant insufficiency predicted C-reactive protein (ß = 0.135, P = .032) and interleukin 10 (ß = -.155, P = .027). Patients with higher antioxidant insufficiency had higher C-reactive protein and lower interleukin 10. Both antioxidant insufficiency (ß = 0.13, P = .049) and higher C-reactive protein (ß = 0.16, P = .019) were independently associated with poorer HRQOL while adjusting for covariates. CONCLUSIONS: Dietary antioxidant insufficiency was associated with increased markers of inflammation and poorer HRQOL. Improvement of diet quality among patients with HF may be a fruitful area of research for enhancing HRQOL.

Lineage switch of KMT2A-rearranged adult B-lineage acute lymphoblastic leukemia following bispecific T-cell engager and monoclonal antibody therapy.

Adult B-lineage acute lymphoblastic leukemia (B-ALL) with t(4;11)(q21;q23) is very rare. It is characterized by mixed-lineage leukemia and has the potential for lineage switching during the treatment course. We report the disease course of a patient with B-ALL with t(4;11)(q21;q23) to demonstrate that close monitoring of cell morphology and immunophenotyping is necessary to capture the lineage switch at an early stage. Cell morphology, immunophenotyping, and cytogenetics were used to evaluate the patient's disease status. A 36-year-old woman was diagnosed with B-ALL with t(4;11)(q21;q23), which encodes the KMT2A::AFF1 fusion. After the initial induction chemotherapy, her disease remained refractory, and the patient received salvage immunotherapy with blinatumomab and inotuzumab ozogamicin. However, the ALL did not respond. Repeated bone marrow examinations unexpectedly revealed the emergence of a major population of monoblasts, in addition to a minor population of the original B lymphoblasts. The patient was diagnosed with disease evolution from B-ALL to mixed-phenotype acute leukemia (MPAL, B/myeloid). We present this case to highlight the potential of KMT2A-rearranged B-ALL to undergo lineage switch following B-cell targeted therapy. Patients with this kind of B-ALL should therefore be closely monitored to capture potential changes in the nature of the disease and prompt appropriate treatment.

Acculturation Strategies and Pap Screening Uptake among Sub-Saharan African Immigrants (SAIs).

Although regular cervical cancer screening can prevent cervical cancer, screening utilization remains low among immigrant population including sub-Saharan African immigrants (SAIs). Acculturation is a complex process, which can lead to adoption of positive or negative health behaviors from the dominant culture. Acculturation strategies are the varying ways in which individuals seek to go about their acculturation by either maintaining or rejecting their own cultural values ip or accepting or rejecting the host culture's cultural values. Cervical cancer screening behaviors among SAI women may be influenced by their acculturation strategies. We conducted a secondary analysis of data to examine the relationship between acculturation strategies and Pap screening among 99 SAI women recruited from community settings. Data were collected on Pap screening behavior and acculturation strategy. Traditionalists and Integrationists were the dominant acculturation strategies; 32.3% women were Traditionalists and 67.7% Integrationists. From the logistic regression models, Integrationists had seven times the odds of having ever been screened compared to Traditionalists (OR = 7.08, 95% CI = 1.54-28.91). Cervical cancer screening interventions should prioritize Traditionalists for cancer screening. Acculturation strategies may be used to tailor cancer prevention and control for SAIs. More research among a larger SAI women sample is warranted to further our understanding of Pap screening patterns and acculturation strategies.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

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Firmiana danxiaensis is an endemic species of Danxia landform in China. Identifying the main driving factors of its distribution can provide scientific basis for the conservation of F. danxiaensis and related habitats. With GeoDetector, we analyzed the correlation (measured by q value) between the spatial distribution of F. danxiaens and its habitat factors in F. danxiaens Nature Reserve in Nanxiong City and the Guangdong Danxia Mountain Tourism Scenic Area (core scenic area). Factors measured in this study included geographical elements (geomorphological type, soil subtype, elevation, slope, aspect) and climatic elements (annual precipitation and annual sunshine hours, mean annual relative humidity and mean annual wind speed). Our results showed that the main habitat factors affecting the spatial distribution of F. danxiaensis were soil subtype, annual sunshine hours, and geomorphologic genesis type. The q values of those three factors were higher than the mean values of all factors. In the pairwise combination of habitat factors, the interaction between geomorphologic genesis types ∩ annual sunshine hours and soil subtypes ∩ annual sunshine hours was enhanced by two factors and the q value was greater than the mean value of all combinations, with a strong correlation. Compared with other factors, the q value of soil subtypes, annual sunshine hours and geomorphologic genesis types were significantly different in the ecological detection of spatial distribution correlation of F. danxiaensis. The spatial distribution of F. danxiaensis was significantly correlated with soil subtypes, geomorphologic genesis types and annual sunshine hours, indicating that the GeoDetector is a useful method for vegetation habitat factor analysis and species distribution prediction.

Racial differences in dietary antioxidant intake and cardiac event-free survival in patients with heart failure.

BACKGROUND: Heart failure is a chronic, burdensome condition with higher re-hospitalization rates in African Americans than Whites. Higher dietary antioxidant intake is associated with lower oxidative stress and improved endothelial function. Lower dietary antioxidant intake in African Americans may play a role in the re-hospitalization disparity between African American and White patients with heart failure. OBJECTIVE: The objective of this study was to examine the associations among race, dietary antioxidant intake, and cardiac event-free survival in patients with heart failure. METHODS: In a secondary analysis of 247 patients with heart failure who completed a four-day food diary, intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, lycopene, vitamins C and E, zinc, and selenium were assessed. Antioxidant deficiency was defined as intake below the estimated average requirement for antioxidants with an established estimated average requirement, or lower than the sample median for antioxidants without an established estimated average requirement. Patients were followed for a median of one year to determine time to first cardiac event (hospitalization or death). Survival analysis was used for data analysis. RESULTS: African American patients had more dietary antioxidant deficiencies and a shorter cardiac event-free survival compared with Whites ( p = .007 and p = .028, respectively). In Cox regression, race and antioxidant deficiency were associated with cardiac event-free survival before and after adjusting for covariates. CONCLUSION: African Americans with heart failure had more dietary antioxidant deficiencies and shorter cardiac event-free survival than Whites. This suggests that encouraging African American patients with heart failure to consume an antioxidant-rich diet may be beneficial in lengthening cardiac event-free survival.

Depressive symptoms and inflammatory biomarkers in patients with heart failure.

BACKGROUND: Inflammation may be a link between depressive symptoms and outcomes in patients with heart failure. It is not clear whether inflammatory markers are independently related to depressive symptoms in this population. AIM: To determine which inflammatory biomarkers are independently associated with depressive symptoms in heart failure. METHODS AND RESULTS: We analyzed data from 428 outpatients enrolled in a heart failure registry (32% female, 61 ± 12 years, 48% New York Heart Association Class III/IV). Depressive symptoms were measured with the Beck Depression Inventory-II. Serum C-reactive protein (CRP), cytokines (interleukin 1 receptor antagonist, 2, 4, 6, 8, 10), tumor necrosis alpha, and soluble receptors sTNFR1 and sTNFR2 were measured with enzyme immunoassay. Multiple regressions were used to determine which biomarkers were associated with depressive symptoms controlling for demographics, heart failure severity, and clinical variables. Twenty-seven percent (n = 119) had depressive symptoms. CRP was related to depressive symptoms after controlling for age and gender, but no inflammatory biomarkers were associated with depressive symptoms after controlling for all variables in the model. CONCLUSIONS: There was no relationship between inflammatory biomarkers and depressive symptoms. Our findings, in combination with prior researchers', suggest there is not a robust relationship between depressive symptoms and individual biomarkers of inflammation in heart failure.

Energetic studies on DNA-peptide interaction in relation to the enthalpy-entropy compensation paradox.

This study aims to interpret the energetic basis of complex DNA-peptide interactions according to a novel allosteric interaction network approach. In common with other designed peptides, five new conjugates incorporating the XPRK or XHypRK motif (Hyp = hydroxyproline) attached to a N-methylpyrrole (Py) tract with a basic tail have been found to display cooperative binding to DNA involving multiple monodentate as well as interstrand bidentate interactions. Using quantitative DNase I footprinting it appears that allosteric communication via cooperative binding to multiple sites on complementary DNA strands corresponds to two different types of DNA-peptide interaction network. Temperature variation experiments using a dodecapeptide RY-12 show that lower temperature (25 °C) favor a circuit type of allosteric interaction network, whereas higher temperatures (31 and 37 °C) afford only a partial-circuit type of network. Circular dichroism studies show that our five peptides induce significant local conformational changes in DNA via the minor groove, with apparently dimeric binding stoichiometry. Isothermal titration calorimetry reveals that these peptides, together with another seven for comparison, are strongly exothermic upon binding to a model 13-mer DNA duplex, characterized by ΔH ranging from -14.7 to -74.4 kcal mol(-1), and also high TΔS ranging from -6.5 to -65.9 kcal mol(-1). Multiple monodentate and bidentate interactions, as well as ionic forces that mediate positive cooperativity in sequence recognition, are consistent with a dramatic decrease in entropy and a 'tightening' effect of DNA conformation. Distinctive enthalpy-entropy compensation (EEC) relationships are demonstrated for the interaction of all twelve designed peptides with DNA, affording a straight line of slope close to unity when ΔH is plotted versus TΔS, with a y-axis intercept (average ΔG) corresponding to -8.5 kcal mol(-1), while the observed ΔG ranges from -8.2 to -9.1 kcal mol(-1) for the peptides. The EEC seen with peptide RY-12 binding to the model duplex persists throughout various incubation temperatures. The net compensation of energy between the favorable negative ΔH and unfavorable negative ΔS components thus constrains the value of net binding free energy ΔG within a remarkably constant range, as is clearly visible in a 3-dimensional energetic plot. We conclude that the preservation of a rather narrowly-defined ΔG value is central to the EEC in DNA-peptide interactions, illuminating the universal EEC paradox commonly found in diverse biochemical reactions.

Commonalities and differences in correlates of depressive symptoms in men and women with heart failure.

OBJECTIVE: (i) To compare the prevalence and severity of depressive symptoms between men and women enrolled in a large heart failure (HF) registry. (ii) To determine gender differences in predictors of depressive symptoms from demographic, behavioral, clinical, and psychosocial factors in HF patients. METHODS: In 622 HF patients (70% male, 61 ± 13 years, 59% NYHA class III/IV), depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). Potential correlates were age, ethnicity, education, marital and financial status, smoking, exercise, body mass index (BMI), HF etiology, NYHA class, comorbidities, functional capacity, anxiety, and perceived control. To identify gender-specific correlates of depressive symptoms, separate logistic regression models were built by gender. RESULTS: Correlates of depressive symptoms in men were financial status (p = 0.027), NYHA (p = 0.001); functional capacity (p < 0.001); health perception (p = 0.043); perceived control (p = 0.002) and anxiety (p < 0.001). Correlates of depressive symptoms in women were BMI (p = 0.003); perceived control (p = 0.013) and anxiety (p < 0.001). CONCLUSIONS: In HF patients, lowering depressive symptoms may require gender-specific interventions focusing on weight management in women and improving perceived functional capacity in men. Both men and women with HF may benefit from anxiety reduction and increased control.

Methylation profiling using degenerated oligonucleotide primer-PCR specific for genome-wide amplification of bisulfite-modified DNA.

DNA methylation is one of the essential epigenetic processes that play a role in regulating gene expression. Aberrant methylation of CpG-rich promoter regions has been associated with many forms of human cancers. The current method for determining the methylation status relies mainly on bisulfite treatment of genomic DNA, followed by methylation-specific PCR (MSP). The difficulty in acquiring a methylation profiling often is limited by the amount of genomic DNA that can be recovered from a given sample, whereas complex procedures of bisulfite treatment further compromise the effective template for PCR analysis. To circumvent these obstacles, we developed degenerated oligonucleotide primer (DOP)-PCR to enable amplification of bisulfite-modified genomic DNA at a genome-wide scale. A DOP pair was specially designed as follows: first 3' DOP, CTCGAGCTGHHHHHAACTAC, where H is a mixture of base consisting of 50% A, 25% T, and 25% C; and second 5' DOP, CTCGAGCTGDDDDDGTTTAG, where D is a mixture of base consisting of 50% T, 25% G, and 25% A. Our results showed that bisulfite-modified DNAs from a cell line, cord blood cells, or cells obtained by laser capture microdissection were amplified by up to 1000-fold using this method. Subsequent MSP analysis using these amplified DNAs on nine randomly selected cancer-related genes revealed that the methylation status of these genes remained identical to that derived from the original unamplified template.