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Arteriovenous fistula is the preferred vascular access for hemodialysis patients. High-flow arteriovenous fistula may cause high-output heart failure. Various procedures are used to reduce high-flow arteriovenous fistula. This study aimed to assess the efficacy of proximal artery restriction combined with distal artery ligation on flow reduction for high-flow arteriovenous fistula and on cardiac function and echocardiographic changes in patients undergoing hemodialysis. A retrospective analysis was performed on data collected from the medical records of patients undergoing hemodialysis with heart failure and high-flow arteriovenous fistula between May 2018 and May 2021. Thirty-one patients were treated with proximal artery restriction (banding juxta-anastomosis of the proximal artery) combined with distal artery ligation (anastomosis distal artery ligation). Changes in the Acute Dialysis Quality Initiative Workgroup cardiac function class, blood pressure, and echocardiography before and 6 months after flow restriction were compared, and post-intervention primary patency was followed-up. The technical success rate of the surgery was 100%, and no surgery-related adverse events occurred. Blood flow and blood flow/cardiac output decreased significantly after flow restriction. Blood flow decreased from 2047.21 ± 398.08 mL/min to 1001.36 ± 240.42 mL/min, and blood flow/cardiac output decreased from 40.18% ± 6.76% to 22.34% ± 7.21% (P <.001). Post-intervention primary patency of arteriovenous fistula at 6, 12, and 24 months was 96.8%, 93.5%, and 75.2%, respectively. The Acute Dialysis Quality Initiative Workgroup cardiac function class improved significantly after 6 months of flow restriction (P <.001). The systolic and diastolic left heart function improved, as evidenced by a significant decrease in left atrial volume index, left ventricular end-diastolic/end-systolic diameters, left ventricular end-diastolic volume, left ventricular mass index, cardiac output, and cardiac index and an increase in lateral peak velocity of longitudinal contraction, average septal-lateral s', and lateral early diastolic peak velocity after flow restriction (P <.05). Systolic pulmonary artery pressure decreased from 32.36 ± 8.56 mmHg to 27.57 ± 8.98 mmHg (P <.05), indicating an improvement in right heart function. Proximal artery restriction combined with distal artery ligation effectively reduced the blood flow of high-flow arteriovenous fistula and improved cardiac function. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that statins may have antitumor effects but their role in rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer. This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013. In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P =.003; OS: HR, 0.62; 95% CI, 0.39–0.96; P =.032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P =.005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P =.043; log-rank P =.028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P =.032). No such association was present in the younger group. Statin use was related to improved survival in older patients with rectal cancer. This observation is important given the low cost and safety of statins as a drug. [ABSTRACT FROM AUTHOR]

Abstract Superadsorbent hydrogel was prepared from lignin and montmorillonite for Cu(II) ions removal, and the chemical structure and morphology of the hydrogel were characterized by FT-IR, XRD, SEM and XPS. The swelling kinetics of the prepared hydrogel was investigated, and the result showed that the swelling process fit the Schott second-order dynamic equation. The influences of pH, contact time, Na+ concentration, and initial Cu(II) ion concentration on adsorption were studied, and the maximum adsorption value was 1.17 mmol/g, and the adsorption was rapid during the initial 5 h period, and copper ions adsorption on the superadsorbent hydrogel is a favorable process. The results also indicated that the adsorption kinetics was in accordance with the pseudo-second-order kinetic model and the adsorption isotherm conformed to the Freundlich model. FT-IR and XPS analysis revealed that the adsorption behavior was mainly due to ion exchange. The desorption ratios of copper ions from the superadsorbent were >0.8, and the regeneration efficiency was >80% after five cycles reuse, and the results show the excellent desorption performance and reusability of the prepared hydrogel. [ABSTRACT FROM AUTHOR]

Adsorbents based on natural polysaccharides have attracted increasing interest because of their low-cost and biodegradability, particularly, polysaccharide-based nanocomposite adsorbents. In this study the xylan/poly(acrylic acid) magnetic nanocomposite hydrogel adsorbent was prepared from wheat straw xylan and Fe 3 O 4 nanoparticles, and its adsorption property was studied on methylene blue removal. The prepared hydrogel adsorbent had a semi-interpenetrating network structure and exhibited a macro-porous structure with interconnected porous channels. Super-paramagnetic characteristic behavior was observed from magnetic analysis using a vibrating sample magnetometer. The optimum condition for methylene blue adsorption on the adsorbent was found at pH 8 with an adsorbent dosage of 3 g/L and an initial concentration of 400 mg/L, and the removal percentage reached above 90%. The adsorption isotherm of methylene blue on the prepared hydrogel adsorbent was fitted to the Langmuir model, and the pseudo-second-order kinetic model could describe the adsorption process. All obtained results indicated that the prepared hydrogel adsorbent is promising for water treatment applications. [ABSTRACT FROM AUTHOR]

Abstract: Background: The mammalian target of rapamycin (mTOR) is known to regulate cell growth, and it also participates in pain transmission as has been recently verified in inflammatory and neuropathic pain models. The targeting of mTOR represents a new strategy for the control of chronic pain. In the present study, we investigated the effect of mTOR in the expression of PSD95 and NR2B-PSD95 or GluA2-PSD95 interaction ratio in a chronic constriction injury (CCI) mice model. Methods: Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were respectively used to assess mechanical allodynia and thermal hyperalgesia after CCI operation and intrathecal injection of rapamycin. Western blot and co-immunoprecipitation were used to investigate the effects of rapamycin on the expression of PSD95 and interaction ratio of NR2B-PSD95 or GluA2-PSD95 in the spinal dorsal horn of mice. Results: Our study demonstrated that the inhibition of spinal mTOR with intrathecal injections of rapamycin (1μg/5μL) for days 1–6 after CCI surgery led to an obvious decrease in CCI-induced neuropathic pain. Rapamycin significantly reduced the PMWT of CCI mice, whereas there was no significant effect on PWTL. The active form of the mTOR signaling pathway (p-mTOR, p-4EBP1 and p-p70S6k) at the spinal level remarkably increased in CCI mice, and rapamycin could inhibit this up-regulation. The increased expression of PSD95 and the interaction ratio of GluA2-PSD95 or NR2B-PSD95 could also be inhibited by intrathecal injection of rapamycin. Conclusion: These data suggest that the mTOR pathway is activated in the spinal dorsal horn in CCI-induced neuropathic pain, and the intrathecal injection of rapamycin can reduce mechanical allodynia. Our findings indicate that spinal mTOR is an important component of CCI-induced neuropathic pain, and mTOR may be a potential target for chronic pain therapy. [Copyright &y& Elsevier]

Abstract: Hydrogels based on hemicellulose of wheat straw were prepared as a novel carrier for controlled drug delivery. The chemical structure and morphology of the hydrogels were characterised using FT-IR and SEM, respectively. The swelling ratios of the hydrogels were determined, and the results showed that the hydrogels were pH-responsive. The swelling kinetics of the hydrogels followed a Fickian diffusion process in media with a pH of 1.5, and water uptake was controlled collaboratively by hydrogel relaxation and water diffusion in media with pH values of 7.4 and 10.0. The degradation test of the hydrogels was conducted under simulated physiological conditions, and both hemicellulose content and the crosslinking density of the hydrogels were major factors that affected the biodegradability of the hemicellulose-based hydrogels. A comparison of the in vitro release of acetylsalicylic acid and theophylline indicated that the drug release was controlled both by the hydrogel and by the intrinsic character of the drug. According to the results presented here, hemicellulose-based hydrogels can be used in biomedical fields, especially for controlled drug release. [Copyright &y& Elsevier]

Abstract: Structural characterization and isolation of lignin and hemicelluloses from crops are very important for industrial utilization. In this paper, the sequential treatments of barley straw using 90% dioxane, 80% acidic dioxane, 100% dimethyl sulfoxide, and 8% NaOH released total 93% of original lignin and 87% of original hemicelluloses. The extractions with acidic dioxane and dimethyl sulfoxide produced the original hemicelluloses and high-condensed lignin mainly from the middle lamella. FT-IR and NMR analyses show that the hemicelluloses of barley straw contain acidic arabinxylans as the major polysaccharides, which are substituted by α-l-arabinofuranose, 4-O-methyl-glucuronic acid, acetyl group (DS=0.13), and xylose at O-3 and/or O-2 of xylan, and lignin contains β-O-4′ as a predominant interunit linkage with high amounts of β-5′ and β-1′. The guaiacyl and syringyl units are more etherified, and the proportion of erythro-β-O-4′ is slightly higher than that of threo-β-O-4′ in the lignin of barley straw. [Copyright &y& Elsevier]

Abstract: In this paper, a new micromachined interdigital coplanar waveguide (CPW) structure has been developed and its characteristics have been studied as a function of transmission line parameters. In interdigital CPW, the ground conductor is thickened by micromachining techniques which is helpful for reducing the interference between the adjacent center conductors while microwave transmits along it. Within the frequency range from 5 to 20GHz, the return loss of this structure has two minimal values whose positions change with the structural parameters. The relative bandwidths reached 23.5% and 9.97% at 8.3 and 16.55GHz while the insertion losses are about 0.33 and 0.5dB/cm, respectively. The interdigital CPW is useful for designing bandpass filter and phase shifter and minimizing the whole size of microelectromechanical system (MEMS) devices. [Copyright &y& Elsevier]

Abstract: Seven residual hemicellulosic preparations (19.6–45.0% of the original hemicelluloses) were extracted from wheat straw pre-treated with various organic solvents using 1.8% H2O2–0.18% cyanamide at 50°C and pH 10.0 for 4h. Their chemical compositions and physicochemical properties were determined using GC, HPLC, GPC, FT-IR and 13NMR spectroscopy. The results indicated that all the residual hemicellulosic preparations were heteropolysaccharides containing xylose, glucose, arabinose, galactose, mannose, rhamnose and 4-O-methyl-α-d-glucopyranosyluronic acid. The predominant monosaccharide was xylose, ranging between 67.7% and 81.9% of the total neutral sugars, composed mainly of l-arabino-(4-O-methyl-d-glucurono)-d-xylan. The content of contaminant lignin in the isolated residual hemicelluloses was 2.89–5.31%. The M w values of the two residual hemicellulosic preparations H6 and H7 (42,710 and 44,080gmol−1, respectively) obtained from the aqueous-alcohol pre-treated straw were much higher than those of H1–H5 (12,980–15,950gmol−1) extracted from the organic acid pre-treated straw. [Copyright &y& Elsevier]

The chemical modification of rice, wheat, rye, and barley straws, and poplar wood fibre using acetic anhydride at different time and temperatures in the absence of solvent and catalyst has been investigated. It was found that the weight percent gain increased with an increment of reaction temperature and time, and the fastest rate of reaction occurred during the initial 1 h acetylation process. The characterization of acetylated straws and poplar wood fibre was performed by FT-IR, solid-state 13C-NMR, and thermal studies. Thermal stability of acetylated straws was found to be higher than the unmodified straws. [Copyright &y& Elsevier]

Bisphenol S (BPS) is an endocrine disruptor which is widely used in commercial plastic products. Previous studies have shown that exposure to BPS has toxic effects on various aspects of mammalian, but there are few reports about reproductive toxicity. In order to investigate the effects of maternal BPS exposure on the reproductive of F1 and F2 female mice, the pregnant mice were orally administered with different dosages of BPS only once every day from 12.5 to 15.5 days post-coitus (dpc). The results showed that maternal BPS exposure to 2 μg per kg of body weight per day (2 μg/kg) and 10 μg/kg accelerated the meiotic prophase I (MPI) of F1 female mice and the expression of the genes related to meiotic were increased. Further studies showed that maternal BPS exposure resulted in a significant increase in the percentage of oocytes enclosed in primordial follicles in the 3 days post-partum (3 dpp) ovaries of F1 female mice. And at the time of 21 days post-partum (21 dpp) in F1 female mice, the number of antral follicles were significantly lower compare to controls. In the study of five-week female mice of F1, we found that BPS disturbed the folliculogenesis, and the maturation rates and fertilization rates of oocytes were significantly decreased. Of note, maternal BPS exposure disrupted H3K4 and H3K9 tri-methylation levels in F1 ovaries. Maternal BPS exposure only affected the cyst breakdown in F2 female mice. Taken together, our results suggest that, maternal BPS exposure impaired the process of meiosis and oogenesis of F1 and F2 offspring, resulting in abnormal follicular development and serious damage to the reproduction. Image 1 • Maternal Bisphenol S exposure accelerated meiosis in the F1 fetus oocytes. • Maternal Bisphenol S exposure impaired oogenesis in F1 and F2 mice. • Maternal Bisphenol S exposure resulted in epigenetic alterations of F1 female mice. [ABSTRACT FROM AUTHOR]

Although there is abundant evidence to demonstrate that maternal smoking during pregnancy will harm the health of future generations, the impact of nicotine use by pregnant woman upon the oogenesis and folliculogenesis of female offspring has not been as widely scrutinized. Here we focus on the effects of nicotine on the meiotic progression of fetal oocytes. The data indicated that in pregnant mice treated with nicotine, intracellular ROS increased in follicles within the fetal ovary. Excessive intracellular hydrogen peroxide (H 2 O 2) and superoxide anion (O 2 -) decreased mitochondrial membrane potential, inducing mitochondrial dysfunction, triggering an autophagic cascade and inhibiting anti-autophagic proteins. Fetal oocytes in F1 offspring of pregnant mice treated with nicotine exhibited a delay in meiotic prophase I, especially from the stage of pachytene to diplotene. In pubertal F1 offspring we observed a reduced number of follicles; the same reduction was also observed in F2 offspring. Of note, we found that melatonin ameliorated nicotine-induced oocyte damage and increased the expression of MnSOD, which decreased the production of nicotine-induced intracellular ROS. In addition, melatonin also maintained normal H3K4 and H3K9 di- and tri-methylation in F1 and F2 ovaries. Taken together, the current evidence suggests that, in the mouse, melatonin could prevent nicotine-impaired fetal oogenesis and folliculogenesis in offspring. Image 1 • Melatonin ameliorates maternal nicotine exposure causes damage to fetal oogenesis. • Melatonin rescued nicotine-induced ROS and mitochondrial dysfunction. • Melatonin prevent nicotine damage transgenerational transmission. [ABSTRACT FROM AUTHOR]

Abstract: This work investigated the characteristics of dissolved organic matter (DOM) in the source water from Huangpu River and treatability by the pre-ozonation, coagulation, filtration, post-ozonation and biologically activated carbon (BAC) process. The molecular weight distribution and DOC of each fraction obtained from membrane filters were analyzed. The results showed that the <3kDa fraction contained mainly DOM from the raw water sample, suggesting that the water had been highly contaminated by anthropogenic activities. The raw water contained more hydrophilic fraction and less hydrophobic fraction, especially the non-acid hydrophilic fraction. Since there was a higher content of DOM in the <3kDa and non-acid hydrophilic fractions, chlorination of the Huangpu River water produced a greater trihalomethane formation potential (THMFP) and haloacetic acid formation potential (HAAFP), which indicated that the low molecular weight DOM and hydrophilic fractions were the major disinfection by-product precursors in the chlorine disinfection process. However, these DOM fractions cannot be effectively removed through conventional water treatment. The combined pre- and post-ozonation BAC process showed better removal efficiency of DOM and DBPFP compared to the conventional process. Furthermore, positive activity and dose-related effect was observed in the raw water extracts and no genetoxicity was observed for the sample from BAC in the Ames test. Therefore, the results of this study suggest that the advanced O3-BAC process is a better alternative for the treatment of drinking water from Huangpu River. [Copyright &y& Elsevier]

Abstract: The decomposition of diethyl phthalate (DEP) in water using UV–H2O2 process was investigated in this paper. DEP cannot be effectively removed by UV radiation and H2O2 oxidation alone, while UV–H2O2 combination process proved to be effective and could degrade this compound completely. With initial concentration about 1.0mg/L, more than 98.6% of DEP can be removed at time of 60min under intensity of UV radiation of 133.9μW/cm2 and H2O2 dosage of 20mg/L. The effects of applied H2O2 dose, UV radiation intensity, water temperature and initial concentration of DEP on the degradation of DEP have been examined in this study. Degradation mechanisms of DEP with hydroxyl radicals oxidation also have been discussed. Removal rate of DEP was sensitive to the operational parameters. A simple kinetic model is proposed which confirms to pseudo-first order reaction. There is a linear relationship between rate constant k and UV intensity and H2O2 concentration. [Copyright &y& Elsevier]

Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT.Methods and materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery.Results: Survivin positivity was related to worse survival, independent of Dukes'' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71).Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. [Copyright &y& Elsevier]

The present study was undertaken to investigate the extractability of the hemicelluloses from bagasse obtained by ultrasound-assisted extraction methods. The results showed that the ultrasonic treatment and sequential extractions with alkali and alkaline peroxide under the conditions given led to a release of over 90% of the original hemicelluloses and lignin. This fact as well as the sugar composition and structural features of the isolated seven hemicellulosic fractions indicated that ultrasonication attacked the integrity of cell walls, cleaved the ether linkages between lignin and hemicelluloses, and increased accessibility and extractability of the hemicelluloses. Increasing alkali concentration from 0.5 to 2 M and alkaline peroxide percentage from 0.5% to 3.0% resulted in degradation of hemicellulosic backbone as shown by a decrease in their molecular weights from 43,580 to 14,470 and 30,180 to 18,130 g mol−1, respectively. However, there were no significant differences in the structural features of the seven sequential alkali- or alkaline peroxide-soluble hemicellulosic fractions, which are composed mainly of l-arabino-(4-O-methyl-d-glucurono)-d-xylans. Ferulic and p-coumaric acids were found to be chemically linked with hemicelluloses. [Copyright &y& Elsevier]

The polymorphism at codon 201 of the “deleted in colorectal carcinoma” (DCC) gene has been liked to susceptibility to colorectal cancer. However, its clinicopathological significance has not been reported. We examined the codon 201 polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did not significantly differ from normal to transitional mucosa and to tumor, but LOH was increased from transitional mucosa to tumor. Almost all of the LOH cases showed the polymorphism. The polymorphism was increased from well/moderately to poorly differentiated and to mucinous carcinoma (P=0.03). The polymorphism was more frequently seen in advanced stages than in earlier stages (P=0.02), and further predicted worse survival (P=0.04). The data suggest that the codon 201 polymorphism of the DCC gene was a target of LOH, and predicted prognosis in colorectal cancer patients. [Copyright &y& Elsevier]

Purpose: To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.Methods and Materials: Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.Results: RhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry-based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.Conclusions: RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways. [ABSTRACT FROM AUTHOR]

Skin-derived stem cells (SDSCs) have the potential to differentiate into gametes and are a potential resource for research and clinical applications. Sufficient amount of primordial germ cells (PGCs) is an important requirement for successful differentiation of SDSCs into gametes in vitro . Retinoic acid (RA), a vitamin A–derived small lipophilic molecule, promotes the growth of PGCs in vivo ; however, the role of RA on the proliferation of PGC-like cells (PGCLCs) derived from SDSCs remains unknown. In this study, SDSCs were induced to differentiate into the embryoid body and cocultured with mouse fibroblasts to form PGCLCs. The proliferation of PGCLCs with the presence of various concentrations of RA was investigated in vitro . Immunofluorescence labeling showed that the 5-Bromo-2-deoxyUridine-positive ratio of PGCLCs was increased after the cells were treated with 5-μM RA, and flow cytometry results showed that the number of cells in the S phase was increased significantly. The messenger RNA expression levels of cell cycle–related genes, CCND1 and CDK2 , were also increased. Furthermore, RA effectively promoted the external proliferation of endogenous PGCs when 11.5-days postcoitum fetal mouse genital ridges were cultured in vitro . In conclusion, 5-μM RA promoted the proliferation of SDSCs-derived PGCLCs and endogenous PGCs. Our study will provide a valuable model system for studying the differentiation of stem cells into gametes in vitro . [ABSTRACT FROM AUTHOR]

Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT. [Copyright &y& Elsevier]

Background & Aims: Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. Methods: Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry. Results: Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2pg/ml, p =0.003) and the validation (142.2 vs. 89.9pg/ml, p =0.004) trials. Serum levels of IL-21 (p =0.005) or HBV-DNA (p =0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4+ and CD8+ T cells during the first 12weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations. Conclusions: Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB. [Copyright &y& Elsevier]

Abstract: Microstructure of a transient liquid phase (TLP) bonded joint between single crystal DD98 and polycrystalline K465 superalloys was investigated by scanning electron microscopy, transmission electron microscopy and X-ray diffraction techniques. After bonding at 1190°C for 2h, many phases formed in the centerline of the bonding zone due to an incompletely solidified liquid interlayer. There are script-like, tree-like and blocky compounds besides solid solution γ phase in this region. The script-like phase is CrB boride that is rich in Cr, the tree-like compound rich in Ni is M23B6 with FCC structure, and the blocky phase enriched in Ti, Ta, and Nb, is MC carbide that resulted from the interdiffusion of C atoms between dissimilar base metals. After TLP bonding, many blocky and fine M6C particles rich in Cr and W appeared in the diffusion zone of the K465 side. A number of blocky and platelet M3B2 borides rich in W, Cr and Mo precipitated in the diffusion zone of the DD98 side. [Copyright &y& Elsevier]

Abstract: In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. qPCR amplification of near-full-length (∼16kb) mtDNA revealed >50% loss of full-length product, whereas amounts of a qPCR product of a nuclear gene (13kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60–70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders. [Copyright &y& Elsevier]

Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer. [Copyright &y& Elsevier]

Abstract: Background and purpose: An exon 2 G4C14→A4T14 polymorphism in the p73 gene was shown to be related to survival in several types of cancers, including colorectal cancer. The purpose was to investigate if this polymorphism was related to survival in rectal cancer patients with or without preoperative radiotherapy. Materials and methods: DNA extracted from tissue of 138 rectal cancer patients that received preoperative radiotherapy or had surgery alone was typed for the polymorphism by PCR using confronting two-pair primers. Results: Among patients, 69% had GC/GC genotype, 27% had GC/AT and 4% had AT/AT. In the radiotherapy group, patients carrying the AT (GC/AT+AT/AT) allele had stronger expression of p53 (p =0.001) and survivin protein (p =0.03) than those carrying the GC/GC genotype. Further, among patients receiving preoperative radiotherapy the GC/GC genotype tended to be related to better survival (p =0.20). Patients with GC/GC genotype, along with negative p53 and weak survivin expression showed better survival than the other patients (p =0.03), even after adjusting for TNM stage and tumor differentiation (p =0.01, RR, 7.63, 95% CI, 1.50–38.74). In the non-radiotherapy group, the polymorphism was not related to survival (p =0.74). Conclusions: Results suggest that the p73 G4C14→A4T14 polymorphism could be one factor influencing outcome of preoperative radiotherapy in rectal cancer patients. [Copyright &y& Elsevier]

Chronic iron overload has slow and insidious effects on heart, liver, and other organs. Because iron-driven oxidation of most biologic materials (such as lipids and proteins) is readily repaired, this slow progression of organ damage implies some kind of biological "memory." We hypothesized that cumulative iron-catalyzed oxidant damage to mtDNA might occur in iron overload, perhaps explaining the often lethal cardiac dysfunction. Real time PCR was used to examine the "intactness" of mttDNA in cultured H9c2 rat cardiac myocytes. After 3-5 days exposure to high iron, these cells exhibited damage to mtDNA reflected by diminished amounts of near full-length 15.9-kb PCR product with no change in the amounts of a 16.1-kb product from a nuclear gene. With the loss of intact mtDNA, cellular respiration declined and mRNAs for three electron transport chain subunits and 16 S rRNA encoded by mtDNA decreased, whereas no decrements were found in four subunits encoded by nuclear DNA. To examine the importance of the interactions of iron with metabolically generated reactive oxygen species, we compared the toxic effects of iron in wild-type and rho° cells. In wild-type cells, elevated iron caused increased production of reactive oxygen species, cytostasis, and cell death, whereas the rho° cells were unaffected. We conclude that long-term damage to cells and organs in iron-overload disorders involves interactions between iron and mitochondrial reactive oxygen species resulting in cumulative damage to mtDNA, impaired synthesis of respiratory chain subunits, and respiratory dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers.Methods and Materials: p73 was immunohistochemically examined on biopsies (unirradiated, n=102), distant (from the large bowel, n=82), and adjacent (adjacent to primary tumor, n=89) normal mucosa samples, primary tumors (n=131), and lymph node metastasis (n=32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT.Results: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (pConclusions: Normal epithelial cells seem more sensitive to RT than tumor cells regarding p73 expression. Patients with p73-negative rectal tumors may have a lower risk of local recurrence after RT. [ABSTRACT FROM AUTHOR]

Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes’ stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT. [Copyright &y& Elsevier]

Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2–negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2–positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors. [Copyright &y& Elsevier]

The female reproductive lifespan is largely determined by the size of primordial follicle pool, which is established in early life. Bisphenol S (BPS), frequently present in plastic products used in daily life, has been demonstrated as an exogenous estrogen-like endocrine disrupting chemical interfering with the endocrine and reproductive systems. However, the molecular mechanisms of its reproductive toxicity remain to be determined. In the present study, we focused on the effect of BPS on the early ovarian folliculogenesis of mice. Our in vivo experiments showed that the treatment with BPS at 2 and 10 μg/kg body weight/day for 3 days induced abnormal germ cell cyst breakdown and primordial follicle assembly in the mouse ovary, further affecting later ovarian differentiation and reducing oocyte quality. In addition, our in vitro study demonstrated that BPS could interact with estrogen receptors (ERs) to induce phosphorylation of JNKs, which is responsible for reducing oocyte adhesion in cysts. Meanwhile, BPS exposure up-regulated Notch signaling pathway to increase the proliferation of granulosa cells precursors. Our study provided new evidence for the adverse effects of BPS on female reproduction, especially after perinatal exposure, and elucidated how it works. Image 1 • Bisphenol S (BPS) exposure results in abnormal germ cell cyst breakdown. • BPS exposure activates the JNKs signaling through estrogen receptors. • BPS exposure increase the proliferation of granulosa cells precursors. [ABSTRACT FROM AUTHOR]