Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1

The NAD-dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD⁺ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX-resistant K562 cells (K562R) in a dose-dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX-induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX-induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase-3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.     

Comparison Between poly(dG-dC)·poly(dG-dC) and DNA Modified by cis-diamminedichloroplatinum (II): Immunological and Spectroscopic Studies

Abstract

The importance of the base composition and of the conformation of nucleic acids in the reaction with the drug cis-diamminedichloroplatinum(II) has been studied by competition experiments between the drug and several double-stranded polydeoxyribonucleotides. Binding to poly(dG)·poly(dC) is larger than to poly (dG-dC)·poly(dG-dC). There is no preferential binding in the competition between poly(dG-dC) ·poly(dG-dC), poly(dA-dC) ·poly(dG-dT) and poly(dA-dG)·poly(dC-dT). In the competition between poly(dG-dC) ·poly (dG-dC) (B conformation) and poly(dG-br⁵dC) ·poly(dG-br⁵dC) (Z conformation), the drug binds equally well to both polynucleotides. In natural DNA, modification of guanine residues in (GC)_n·(GC)_nsequences by the drug has been revealed by the inhibition of cleavage of these sequences by the restriction enzyme BssHII. By means of antibodies to platinated poly(dG-dC), it is shown that some of the adducts formed in platinated poly(dG-dC) are also formed in platinated pBR322 DNA. The type of adducts recognized by the antibodies is not known. Thin layer chromatography of the products after chemical and enzymatic hydrolysis of platinated poly(dG-dC) suggests that interstrand cross-links are formed. Finally, the conformations of poly(dG-m⁵dC) modified either by cis-diamminedichloroplatinum(II) or by trans-diammine- dichloroplatinum(II) have been compared by circular dichroism. Both the cis-isomer and the trans-isomer stabilize the Z conformation when they bind to poly(dG-m⁵dC) in the Z conformation. When they bind to poly(dG-m⁵dC) in the B conformation, the conformations of poly(dG-m⁵dC) modified by the cis or the trans-isomer are different. Moreover, the cis-isomer facilitates the B form-Z form transition of the unplatinated regions while the trans-isomer makes it more difficult.     

Variation in embolism occurrence and repair along the stem in drought‐stressed and re‐watered seedlings of a poplar clone

Root pressure and plasma membrane intrinsic protein (PIP) availability in the xylem have been recognized to participate in the refilling of embolized conduits, yet integration of the two mechanisms has not been reported in the same plant. In this study, 4‐month‐old seedlings of a hybrid poplar (Populus alba × Populus glandulosa) clone 84K were subjected to two contrasting soil‐water treatments, with the drought treatment involving withholding of water for 17 days to reduce the soil‐water content to 10% of the saturated field capacity, followed by a re‐watering cycle. The percentage loss of stem hydraulic conductance (PLC) sharply increased, and stomatal conductance and photosynthesis declined in response to drought stress; these processes were gradually restored following the subsequent re‐watering. Embolism was most severe in the middle portions of the stem, followed by the basal and top portions of the stems of seedlings subjected to drought stress and subsequent re‐watering. Although drought stress eliminated root pressure, re‐watering partially restored it in a short period of time. The expression of PIP genes in the xylem was activated by drought stress, and some PIP genes were further stimulated in the top portion after re‐watering. The dynamics of root pressure and differential expression of PIP genes along the stem coincided with changes in PLC, suggesting that root pressure and PIPs work together to refill the embolized vessels. On the basis of the recovery dynamics in PLC and g_smax (maximum stomatal conductance) after re‐watering, the stomatal closure and xylem cavitation exhibited fatigue due to drought stress.     

The emission of floral scent from Lilium ‘siberia’ in response to light intensity and temperature

Floral scent is an important part of volatile compounds emitted from plants, and is influenced by many environmental factors. In this study, the floral scent emitted from Lilium ‘siberia’, a common breed of lily, was collected by dynamic headspace at different levels of light intensity (0, 100, 300, 600, 1,000, and 1,500 μmol m^?2 s^?1) and temperature (10, 20, 30, and 40 °C). Using the automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) technique, the components and release amounts were subsequently identified to investigate the influence of light and temperature on the emission of floral scent. The results revealed that the numbers and release amounts of floral scent components were significantly influenced by light intensity and temperature, showing the similar pattern: first increasing and then decreasing. After light intensity treatment, the maximum numbers and release amounts mainly appeared at 600 and 1,000 μmol m^?2 s^?1. For temperature treatment, 30 °C resulted in the highest numbers and release amounts of the floral scent components. At different levels of light intensity and temperature, terpenoid compounds showed the highest numbers and release amounts among the component categories. α-Ocimene and linalool were the two terpenoid compounds with the highest release amounts, and accounted for the highest proportion. The results obtained provide evidence that both light intensity and temperature trigger the emission of floral scent. The particular response mechanisms must be investigated in future research.     

Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

The Role of Mitochondrial DNA Mutations in Hearing Loss

Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of hearing loss. Of these, the homoplasmic A1555G and C1494T mutations at the highly conserved decoding site of the 12S rRNA gene are well documented as being associated with either aminoglycoside-induced or nonsyndromic hearing loss in many families worldwide. Moreover, five mutations associated with nonsyndromic hearing loss have been identified in the tRNA^Ser(UCN) gene: A7445G, 7472insC, T7505C, T7510C, and T7511C. Other mtDNA mutations associated with deafness are mainly located in tRNA and protein-coding genes. Failures in mitochondrial tRNA metabolism or protein synthesis were observed from cybrid cells harboring these primary mutations, thereby causing the mitochondrial dysfunctions responsible for deafness. This review article provides a detailed summary of mtDNA mutations that have been reported in deafness and further discusses the molecular mechanisms of these mtDNA mutations in deafness expression.     

Infrequent Breakfast Consumption Is Associated with Higher Body Adiposity and Abdominal Obesity in Malaysian School-Aged Adolescents

Unhealthy dietary pattern increases the risk of obesity and metabolic disorders in growing children and adolescents. However, the way the habitual pattern of breakfast consumption influences body composition and risk of obesity in adolescents is not well defined. Thus, the aim of the present study was to assess any associations between breakfast consumption practices and body composition profiles in 236 apparently healthy adolescents aged 12 to 19 years. A self-administered questionnaire on dietary behaviour and lifestyle practices and a dietary food frequency questionnaire were used. Body composition and adiposity indices were determined using standard anthropometric measurement protocols and dual energy χ-ray absorptiometry (DXA). Mean age of the participants was 15.3±1.9 years. The majority of participants (71.2%) fell in the normal body mass index (BMI) ranges. Breakfast consumption patterns showed that only half of the participants (50%) were consuming breakfast daily. Gender-specific multivariate analyses (ANCOVA) showed that in both boys and girls, those eating breakfast at least 5 times a week had significantly lower body weight, body mass index (BMI), BMI z-scores, waist circumference, body fat mass and percent body fat (%BF) compared to infrequent breakfast eaters, after adjustment for age, household income, pubertal status, eating-out and snacking practices, daily energy intakes, and daily physical activity levels. The present findings indicate that infrequent breakfast consumption is associated with higher body adiposity and abdominal obesity. Therefore, daily breakfast consumption with healthy food choices should be encouraged in growing children and adolescents to prevent adiposity during these critical years of growth.