Circulating levels of adipocytokine omentin-1 in patients with renal cell cancer

Renal cell carcinoma (RCC) is the fifth most common cancer worldwide, and becomes one of the leading causes of genitourinary cancer-related death in both males and females. Genetic alternations, alcohol consumption, occupationally harmful exposure and even obesity are well-established risk factors of RCC. Omentin-1 is a plasma adipokine synthesized in visceral adipose tissue, and its circulating serum concentration alters not only in conditions associated with insulin resistance such as Polycystic Ovary Syndrome (PCOS), but also in colorectal cancer and prostate cancer. To our best knowledge, the relationship between omentin-1 and RCC has not been clarified previously. Thus, we evaluated serum omentin-1 levels in RCC patients in the current matched case-control study. Forty-one patients newly diagnosed with RCC and forty-two healthy controls confirmed by the comprehensive medical examination were assessed. The omentin-1 concentrations were determined via utilizing enzyme-linked immunosorbent assays (ELISA) in the paired groups, in which the patients and healthy controls had no statistically significant differences in gender, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist-hip ratio (WHR), estimate glomerular filtration rate (eGFR), body-mass index (BMI) and biochemical parameters. The omentin-1 levels in healthy people were 9.86 ± 1.44 ng/mL and the circulating omentin-1 levels were dramatically decreased to 3.62 ± 0.76 ng/mL in RCC patients (p < 0.001). Besides, we revealed a negative correlation between omentin-1 with WHR (r = −0.261, p = 0.017) and BMI (r = −0.310, p = 0.004), further indicating BMI was the main influential factor on omentin-1 levels (p = 0.0091). Follow-up studies would be conducted to establish the concrete mechanisms underlying the altered circulating levels of omentin-1 and elucidate the interaction between “RCC complex system” and adipose tissues, which may together provide promising and novel pharmacological insights for RCC theragnosis in the near future.     

Oral cancer,cigarette smoke and mitochondrial 18 kDa translocator protein (TSPO) — In vitro,in vivo,salivary analysis

Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Δψ_m), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p < 0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133 ± 643 fmol/mg protein and 6956 ± 549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p < 0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p < 0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p < 0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p < 0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer.     

Polymorphisms of glutathione-S-transferase M1 and T1 and prostate cancer risk in a Tunisian population

Several genes involved in the metabolism of carcinogenesis have been found to be polymorphic in the human population, and specific alleles are associated with increase risk of cancer of various sites. This study is focused on the polymorphic enzymes glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) that involved in the detoxification of many xenobiotics involved in the etiology of prostate cancer. Objective. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 110 incident CaP cases and 122 controls. Results. The probability of having CaP was increased in men who had homozygous deleted (non-functional) genotypes at GSTT1 (OR = 2.17; 95% CI = 1–3.79) but not GSTM1 (OR = 0.89; 95% CI = 0.66–1.88). Hence, individuals lacking the GSTT1 gene are at approximately twofold higher risk of developing prostate cancer in comparison with individuals with at least one active allele in the GSTT1 locus. Conclusion. These results suggest that GSTT1 is associated with CaP risk. The effect of smoking associated with the GSTT10/0 genotype was not found to affect the risk of prostate cancer.     

A novel disintegrin protein from Naja naja venom induces cytotoxicity and apoptosis in human cancer cell lines in vitro

Animal venoms and toxins are potential bioresources that have been known to mankind as a therapeutic tool for more than a century through folk and traditional medicine. The purified “disintegrin protein” (64 kDa) from the venom of the Indian cobra snake (Naja naja) exhibited cytotoxic effects of various types of human cancer cell lines such as breast cancer (MCF-7), lung cancer (A549) and liver cancer (HepG2). In vitro cytotoxicity, DNA fragmentation, an apoptotic assay and a cell cycle analysis were performed to evaluate the anticancer activity of disintegrin against the above cell lines. The IC₅₀ value of disintegrin was determined to be 2.5 ± 0.5 μg/mL, 3.5 ± 0.5 μg/mL, and 3 ± 0.5 μg/mL for the MCF-7, A549 and HepG2 cell lines respectively. Moreover, the increased distribution of G0/G1 and S phase led to decreased populations of cells in the G2/M phase of MCF-7, HepG2 and A549 cells.     

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM).Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m² vs. 21.9 ± 2.0 kg/m² vs. 21.4 ± 1.9 kg/m²; P>.05) were prospectively recruited.Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 μg/dL vs. 297 ± 100 μg/dL; P>.05).Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.     

CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population

AimsIn this study, the effects of four single nucleotide polymorphisms (SNPs), ? 3860G > A, ? 2467delT, ? 739T > G and ? 163C > A, of CYP1A2 gene on lung cancer were evaluated in Tunisian population.Main methodsFour polymorphisms of CYP1A2 gene were analysed in 109 healthy smokers and in 101 lung cancer cases, including 63 with squamous cell carcinoma (SCC) and 41 with adenocarcinoma (AD). The genotyping for the SNPs ? 3860 G > A, ? 2467delT, ? 739T > G and ? 163C > A was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis.Key findingsThe results showed that smokers with CYP1A2 gene polymorphisms were associated with an increased risk for the development of lung AD. There was however no significant increased risk of developing lung SCC in smokers having CYP1A2 gene polymorphisms. An increased risk of developing AD was observed in smokers who are carriers of at least one copy of ? 3680A or ? 739G giving a significant odds ratio (OR) of 6.02 (CI = 2.91–12.9) and 3.01 (CI = 1.54–5.98), respectively.SignificanceThese genotyping data are consistent with the hypothesis that tobacco-specific-N-nitrosamines (TSN) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major contributors to the development of lung AD and that CYP1A2 gene product plays an important role in the metabolic activation of NNK. This study suggests that SNPs of CYP1A2 could be considered as promising biomarkers in the aetiology of lung AD in smokers.     

Clinical significance of serum transforming growth factor-β1 in lung cancer

Background: Transforming growth factor-β1 (TGF-β1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-β1 levels in patients with lung cancer and analyze the relationship between TGF-β1 and existing tumor markers for lung cancer. Methods: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-β1 was assessed alone and in combination with existing tumor markers for lung cancer. Results: Serum TGF-β1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6 × 10⁵ (0.4 × 10⁵, 0.9 × 10⁵) pg/ml vs 0.5 × 10⁵ (0.3 × 10⁵, 0.7 × 10⁵) pg/ml, P = 0.040]. Although there was a positive correlation between serum TGF-β1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P = 0.116). The ability of serum TGF-β1 to discriminate lung cancer at a cutoff value of 79,168 pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-β1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R = 0.308, P = 0.020) and neuron-specific enolase (NSE; R = 0.558, P = 0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-β1 levels. Conclusion: Quantification of serum TGF-β1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.     

Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations

Polymorphisms in 3′ untranslated region (UTR) of cancer-related genes might affect their regulation by microRNAs (miRNAs) and thereby contribute to carcinogenesis. In this study, we screened single nucleotide polymorphisms (SNPs) in 3′ UTR of cancer-related genes and investigated their effects on risk of lung cancer. First, we genotyped seven SNPs in a Chinese Han population with 600 lung cancer patients and 600 matched healthy controls and found that compared with the TT genotype of rs2239680 in 3′ UTR of baculoviral IAP repeat containing 5 (BIRC5), C allele was associated with a significantly increased risk of lung cancer and advanced pathologic stage, with the odds ratio for participants carrying the CT or CC genotype being 1.50 [95% confidence interval (CI) 1.20–1.89, P < 0.01] and 2.29 (95% CI 1.64–3.18, P < 0.01), respectively. These results were further replicated and confirmed in another independent population with 1000 lung cancer cases and 1000 matched healthy controls. In support of the postulation that the 3′ UTR SNP may directly affect miRNA-binding site, reporter gene assays indicated BIRC5 was a direct target of miR-335, and the rs2239680 T > C change resulted in altered regulation of BIRC5 expression. Moreover, BIRC5 was over expressed in lung cancer tissues compared with the normal lung tissues, and the protein levels of BIRC5 correlated with SNP genotypes in normal lung tissues. Our findings defined a 3′ UTR SNP in human BIRC5 oncogene that may increase individual susceptibility to lung cancer probably by attenuating the interaction between miR-335 and BIRC5.     

EPID-based in vivo dosimetry for stereotactic body radiotherapy of non-small cell lung tumors: Initial clinical experience

PurposeEPID-based in vivo dosimetry (IVD) has been implemented for stereotactic body radiotherapy treatments of non-small cell lung cancer to check both isocenter dose and the treatment reproducibility comparing EPID portal images.Methods15 patients with lung tumors of small dimensions and treated with volumetric modulated arc therapy were enrolled for this initial experience. IVD tests supplied ratios R between in vivo reconstructed and planned isocenter doses. Moreover a γ-like analysis between daily EPID portal images and a reference one, in terms of percentage of points with γ-value smaller than 1, P_γ<1, and mean γ-values, γ_mean, using a local 3%–3 mm criteria, was adopted to check the treatment reproducibility. Tolerance levels of 5% for R ratio, P_γ<1 higher than 90% and γ_mean lower than 0.67 were adopted.ResultsA total of 160 EPID images, two images for each therapy session, were acquired during the treatment of the 15 patients. The overall mean of the R ratios was equal to 1.005 ± 0.014 (1 SD), with 96.9% of tests within ± 5%. The 2 D image γ-like analysis showed an overall γ_mean of 0.39 ± 0.12 with 96.1% of tests within the tolerance level, and an average P_γ<1 value equal to 96.4 ± 3.6% with 95.4% of tests with P_γ<1 > 90%. Paradigmatic discrepancies were observed in three patients: a set-up error and a patient morphological change were identified thanks to CBCT image analysis whereas the third discrepancy was not fully justified.ConclusionsThis procedure can provide improved patient safety as well as a first step to integrate IVD and CBCT dose recalculation.     

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

Background: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. Patients and methods: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. Results: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P > 0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P = 0.55). Conclusion: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men.     

Over-production of human interferon-γ by HCDC of recombinant Escherichia coli

A simple fed-batch process was developed using a modified variable specific growth rate feeding strategy for high cell density cultivation of Escherichia coli BL21 (DE3) expressing human interferon-gamma (hIFN-γ). The feeding rate was adjusted to achieve the maximum attainable specific growth rate during fed-batch cultivation. In this method, specific growth rate was changed from a maximum value of 0.55 h⁻¹ at the beginning of feeding and then it was reduced to 0.4 h⁻¹ at induction time.The final concentration of biomass and IFN-γ was reached to ∼115 g l⁻¹ (DCW) and 42.5 g(hIFN-γ) l⁻¹ after 16.5 h, also the final specific yield and overall productivity of recombinant hIFN-γ (rhIFN-γ) were obtained 0.37 g(hIFN-γ) g⁻¹ DCW and 2.57 g(hIFN-γ) l⁻¹ h⁻¹, respectively. According to available data this is the highest specific yield and productivity that has been reported for recombinant proteins production yet.     

5-((1-Aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones as potential anticancer agents with anti-inflammatory properties

A series of novel 5-((1-aroyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (3a–z) have been evaluated for in vitro cytotoxicity against a panel of 60 human tumor cell lines. Compound 3k exhibited the most potent growth inhibition against melanoma MDA-MB-435 cells (GI₅₀ = 850 nM), against leukemia SR cancer cells (GI₅₀ = 1.45 μM), and OVCAR-3 (GI₅₀ = 1.26 μM) ovarian cancer cell lines. The structurally related compound 3s had a GI₅₀ value of 1.77 μM against MDA-MB-435 cells. The N-naphthoyl analogue 3t had GI₅₀ values of 1.30 and 1.91 μM against HOP-92 non-small cell lung cancer and MDA-MB-435 melanoma cell lines, respectively. The related analogue 3w had GI₅₀ values of 1.09 μM against HOP-92 non-small cell lung cancer cell lines. Interestingly, docking of the two active molecules 3k and 3w into the active site of COX-2 indicates that these compounds are COX-2 ligands with strong hydrophobic and hydrogen bonding interactions. Thus, compounds 3k, 3t, 3s, and 3w constitute a new class of anticancer/anti-inflammatory agents that may have unique potential for cancer therapy.     

New prenylated isoflavonoids as protein tyrosine phosphatase 1B (PTP1B) inhibitors from Erythrina addisoniae

Bioassay-guided fractionation of the EtOAc extract of the root of Erythrina addisoniae (Leguminosae) resulted in the isolation of four new (1–4), along with 2 known prenylated isoflavonoids (5–6). The structures of the isolates were assigned on the basis of spectroscopic data analysis, focusing on interpretation of 1D and 2D NMR, and MS data. All the isolates were evaluated for their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), as well as their growth inhibition on MCF7, adriamycin-resistant MCF7 (MCF7/ADR), and MDA-MB-231 breast cancer cell lines. Compounds which exhibited PTP1B inhibitory activity (IC₅₀ values ranging from 4.6 ± 0.3 to 24.2 ± 2.1 μM) showed potential cytotoxic activity (IC₅₀ values ranging from 3.97 ± 0.17 to 11.4 ± 1.9 μM). Taken together, our data suggest that prenylated isoflavonoids, especially the isoflavone-type skeleton could be considered as new lead compounds against breast cancer via PTP1B inhibition.     

Does consanguinity lead to decreased incidence of breast cancer?

Background: In the Middle East region, consanguinity remains to be a central feature where it has shown an increasing trend. Breast cancer is an extremely complex disease, characterized by a progressive multistep process caused by interactions of both environmental and genetic factors. Aim: The aim of this study was to examine the possible effect of consanguinity on the risk of breast cancer in a population with a high rate of consanguinity and find the associated risk-modifying factors. Subjects and methods: The study included 167 Qatari and other Arab expatriates women with breast cancer and 341 age and ethnicity matched control women. A questionnaire that included the socio-demographic information, type of consanguinity, medical history, life style habits, dietary intake and tumor grade was designed to collect, the information of cases and controls. A total number of 214 breast cancer patients were approached and 167 cases completed the questionnaires with a response rate of 78%. Of the 417 healthy women who agreed to participate in this study, 341 responded to the questionnaire (81.8%). Results: The study revealed that the rate of parental consanguinity was lower in breast cancer patients (24%) than in controls (32.3%) (p = 0.062). Female controls were slightly younger (46.5 ± 11.9) than breast cancer patients (48.4 ± 10.7). Breast cancer incidence was significantly higher in Qatari women (34.1%) compared to other Arab women (65.9%) (p = 0.034). A significant difference was noted only in occupation of the studied women between cases and controls (p < 0.001). Overweight (46.7%) and obesity (32.9%) were significantly higher in female breast cancer patients compared to controls (p = 0.028). Overall, the mean coefficient of consanguinity was lower in breast cancer patients (0.014) than in controls (0.018) (p = 0.0125). Family history of breast cancer was significantly more often in breast cancer patients (14.4%) than in controls (6.2%) (p = 0.002). However, the family history of breast cancer was more often positive in cases of non-consanguineous parents (15.7%) than cases of consanguineous parents (10.0%). Conclusion: The present study revealed the lack of association between of breast cancer and the parental consanguinity in Arab women residing in Qatar. The family history of breast cancer and the body mass index (BMI) are highly associated with breast cancer.     

Kinetic analysis of photosynthetic growth and photohydrogen production of two strains of Rhodobacter Capsulatus

Two mutants of Rhodobacter Capsulatus (JP91 and IR3), a photosynthetic purple non-sulfur bacterium, were grown in a batch photobioreactor under illumination with 30 mmol l⁻¹ dl-lactate and 5 mmol l⁻¹ l-glutamate as carbon and nitrogen source, respectively. Bacterial growth was measured by monitoring the increase in absorbance at 660 nm. The photosynthetic growth processes under different cultivated temperatures are well fitted by a specific logistic model to analyze the kinetics of photosynthetic growth of two strains, thus the apparent growth rates (k) of these photosynthetic bacteria, the variations of cell dry weight (CDW) as well as their relationship with temperature are obtained. In present work, k is (0.1465 ± 0.0146), (0.2266 ± 0.0207) and (0.3963 ± 0.0257) h⁻¹ for JP91 and (0.1117 ± 0.0122), (0.1218 ± 0.0133) and (0.2223 ± 0.0152) h⁻¹ for IR3 at 26, 30 and 34 °C, respectively. And the difference between CDW_max and CDW₀ is (0.8997 ± 0.0097), (0.8585 ± 0.0093) and (0.9241 ± 0.0099) g l⁻¹ for JP91 and (0.8167 ± 0.0089), (0.7878 ± 0.0086) and (0.8358 ± 0.0091) g l⁻¹ for IR3 at 26, 30 and 34 °C, respectively. Also real-time monitoring of hydrogen production rates is acquired by recording the flow rates of photohydrogen for these two strains under different temperatures. The effects of temperature on the bacteria growth, hydrogen production capability and substrate conversion efficiency are discussed based on these results. The most preferment temperature, 30 °C, showed good substrate conversion efficiency of 52.7 and 68.2% for JP91 and IR3, respectively.     

The effects of mitochondrial complex I blockade on ATP and permeability in rat pulmonary microvascular endothelial cells in culture (PMVEC) are overcome by coenzyme Q1 (CoQ1)

In isolated rat lung perfused with a physiological saline solution (5.5 mM glucose), complex I inhibitors decrease lung tissue ATP and increase endothelial permeability (K_f), effects that are overcome using an amphipathic quinone (CoQ₁) [Free Radic. Biol. Med. 65:1455–1463; 2013]. To address the microvascular endothelial contribution to these intact lung responses, rat pulmonary microvascular endothelial cells in culture (PMVEC) were treated with the complex I inhibitor rotenone and ATP levels and cell monolayer permeability (PS) were measured. There were no detectable effects on ATP or permeability in experimental medium that, like the lung perfusate, contained 5.5 mM glucose. To unmask a potential mitochondrial contribution, the glucose concentration was lowered to 0.2 mM. Under these conditions, rotenone decreased ATP from 18.4±1.6 (mean±SEM) to 4.6±0.8 nmol/mg protein, depolarized the mitochondrial membrane potential (Δψ_m) from −129.0±3.7 (mean±SEM) to −92.8±5.5 mV, and decreased O₂ consumption from 2.0±0.1 (mean±SEM) to 0.3±0.1 nmol/min/mg protein. Rotenone also increased PMVEC monolayer permeability (reported as PS in nl/min) to FITC–dextran (~40 kDa) continually over a 6 h time course. When CoQ₁ was present with rotenone, normal ATP (17.4±1.4 nmol/mg protein), O₂ consumption (1.5±0.1 nmol/min/mg protein), Δψ_m (−125.2±3.3 mV), and permeability (PS) were maintained. Protective effects of CoQ₁ on rotenone-induced changes in ATP, O₂ consumption rate, Δψ_m, and permeability were blocked by dicumarol or antimycin A, inhibitors of the quinone-mediated cytosol–mitochondria electron shuttle [Free Radic. Biol. Med. 65:1455–1463; 2013]. Key rotenone effects without and with CoQ₁ were qualitatively reproduced using the alternative complex I inhibitor, piericidin A. We conclude that, as in the intact lung, PMVEC ATP supply is linked to the permeability response to complex I inhibitors. In contrast to the intact lung, the association in PMVEC was revealed only after decreasing the glucose concentration in the experimental medium from 5.5 to 0.2 mM.     

Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men

PurposeTranslesion DNA synthesis (TLS) plays an important role in promoting replication through DNA lesions. Genetic polymorphisms in TLS genes may have potential roles in lung cancer development in humans.MethodsWe evaluated the association between genetic variants in six TLS genes and the risk and survival of lung cancer in a case–control study in China. Included in the study are 224 lung cancer patients and 448 healthy controls.ResultsCarriers of the G allele of POLκ rs5744724 had significantly reduced risk of lung cancer (odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.44–0.89), comparing with those carrying the C allele, and the AA genotype of PCNA rs25406 was also associated with significantly decreased cancer risk compared with the major homozygote alleles (OR = 0.47, 95% CI: 0.25–0.86). Haplotype analysis showed that subjects with the POLκ C-G (rs5744533–rs5744724) haplotype had decreased risk of lung cancer (OR = 0.69, 95% CI: 0.49–0.98), comparing with those carrying the C-C haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were independent prognostic factors for lung cancer survival with hazard radio (HR) 1.54 (95% CI: 1.12–2.12) and 1.44 (95% CI: 1.06–1.97) respectively.ConclusionsOur findings suggested that genetic variants in POLκ and PCNA genes may play roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung cancer survival in Chinese men.     

Chromate reduction by resting cells of Achromobacter sp. Ch-1 under aerobic conditions

Chromate reduction was carried out by resting cells of Achromobacter sp. Ch-1 with lactate as electron donor under aerobic conditions. The reduction activity of the samples supplemented with lactate was two times as those without lactate. The reduction rate was influenced by initial pH and lactate concentration. Under the optimal conditions, pH 9.0 and 4000 mg l⁻¹ lactate supplement, reduction rate was 5.45 mg l⁻¹ min⁻¹. The reduction rate decreased with increasing of Cr(VI) concentrations and increased with cell densities proportionally. The maximum reduction limit of Ch-1 cells was obtained at 2107 mg l⁻¹ of Cr(VI).     

Production of an anti-MUC1 C595 dbFv antibody fragment in recombinant Escherichia coli

The production of C595 diabody fragment (dbFv) in Escherichia coli (E. coli) HB2151 clone has been explored. The comparison of fermentation processes mode demonstrated that a higher biomass inoculum operation enhanced C595 dbFv production. It was demonstrated that a concentration of 12.1 mg l⁻¹ broth of dbFv and a cell concentration of 23.6 g l⁻¹ broth were achieved at the end of 75 l fermentation.