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Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs ...when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD+ to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells.
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•Lactate supports lysosomal acidification and autophagy in cancer•Lactate oxidation by LDHB yields protons that fuel lysosomal V-ATPase•Targeting LDHB selectively blocks autophagy in oxidative and glycolytic cancer cells•Targeting LDHB is a promising anticancer approach
Brisson et al. show that lactate dehydrogenase B (LDHB) is critical for lysosomal activity and autophagy in cancer cells. Silencing LDHB selectively inhibits the proliferation of both oxidative and glycolytic cancer cells over normal cells, suggesting inhibition of LDHB as a promising anticancer approach.
Summary
Background
Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs).
Aim
To evaluate the accuracy of faecal chitinase 3‐like 1(CHI3L1) ...compared to calprotectin in detecting endoscopic activity in IBD.
Methods
Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut‐off value was determined using a receiver‐operating curve.
Results
In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 μg/g showing a sensitivity of 90.5% and a specificity of 59.1%.
In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 μg/g showing a sensitivity of 86.4% and a specificity of 80.0%.
Conclusion
Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.
We evaluated the ability of three mosquito species (Aedes caspius, Aedes detritus, Culex pipiens), collected in southern France and Tunisia, and of different laboratory-established colonies (Aedes ...aegypti, Aedes albopictus, Aedes vexans, Anopheles gambiae, Culex pipiens, Culex quinquefasciatus) to disseminate two strains of Rift Valley fever virus (RVFV), the virulent ZH548 and the avirulent Clone 13. After feeding on an infectious blood meal at 10(8.5) plaque-forming units/mL, females were maintained at 30 degrees C for 14 days. Surviving females were tested for the presence of virus on head squashes. Disseminated infection rate corresponds to the number of females with disseminated infection among surviving females. Among field-collected mosquitoes, Cx. pipiens was the most susceptible species with disseminated infection rates ranging from 3.9% to 9.1% for French strains and up to 14.7% for Tunisian strains. Among laboratory-established colonies, Ae. aegypti from Tahiti exhibited the highest disseminated infection rates: 90% when infected with ZH548 and 72.6% with Clone 13. The presence of competent Cx. pipiens in southern France and Tunisia indicates the potential for RVFV epizootics to occur if the virus was introduced into countries of the Mediterranean basin.
Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive ...within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin β. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin α and meprin β. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Isoenzyme variation was assessed in 79 mosquito samples of Aedes aegypti, and susceptibility to a dengue 2 virus strain was evaluated in 83 samples. Analysis of FST values, differentiation indexes, ...and geographic distances separating populations revealed that genetic differences between populations depended on the species' history of migration and colonization. Three major clusters were identified: (1). the sylvan form, Ae. ae. formosus, from West Africa and some islands in the Indian Ocean; (2). the domestic form, Ae. ae. aegypti, from Southeast Asia and South America; and (3). Ae. ae. aegypti populations from the South Pacific islands. Two groups were identified on the basis of susceptibility to the dengue virus: (1). populations with high infection rates, mostly the Ae. ae. aegypti form, and (2). mosquitoes with lower infection rates, specifically Ae. ae. formosus. Other evolutionary and epidemiological implications of the genetic variability of Ae. aegypti are also discussed.
To identify the mosquito species able to sustain the transmission of West Nile Virus (WNV) in the Camargue region (the main WNV focus of southern France), we assessed the vector competence of Culex ...modestus and Culex pipiens, the most abundant bird-feeders, and Aedes caspius, the most abundant mammophilic species occasionally found engorged with avian blood. Female mosquitoes were exposed to the infectious meal (10(10.3) plaque forming units (PFU)/mL) by membrane feeding, and hold at 26 degrees C. After the incubation period, disseminated infection was assessed by WNV detection using an indirect fluorescent antibody assay (IFA) on head squashes, and the transmission rate was assessed by the presence of WNV RNA in salivary secretions with a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). After 14 incubation days, the disseminated infection and the transmission rates were 89.2% and 54.5% for Cx. modestus, 38.5% and 15.8% for Cx. pipiens, and 0.8% and 0 for Ae. caspius. Culex modestus was found to be an extremely efficient laboratory WNV vector and could thus be considered the main WNV vector in wetlands of the Camargue. Culex pipiens was a moderately efficient laboratory WNV vector, but in dry areas of the region it could play the main role in WNV transmission between birds and from birds to mammals. Aedes caspius was an inefficient vector of WNV in the laboratory, and despite its high densities, its role in WNV transmission may be minor in southern France.
In Crohn's disease (CD) the deficiency of mannan-binding lectin (MBL) is associated with an increased prevalence of anti-Saccharomyces cerevisiae antibodies (ASCA) and with complicated phenotypes of ...the disease. However, the role of MBL in intestinal inflammation is currently unclear. A study was undertaken to analyse local MBL expression in human intestine and the consequences of MBL deficiency in experimental colitis and yeast infection.
ASCA were measured by ELISA. MBL was assessed by ELISA and quantitative PCR. Wild type and MBL-deficient mice were administered dextran sulfate sodium (DSS) in the presence or absence of viable Candida albicans or adhesive invasive Escherichia coli (AIEC). Mice were infected with C albicans to assess generation of anti-yeast mannan antibodies.
MBL expression was virtually undetectable in the intestinal mucosa of both healthy controls and patients with CD, irrespective of macroscopic inflammation, indicating that systemic MBL must be responsible for the reduced risk of complicated disease in MBL-competent patients with CD. MBL-deficient mice showed enhanced DSS colitis upon oral challenge with C albicans or AIEC. C albicans could be recovered from the kidneys of colitic/C albicans-fed MBL-deficient, but not wild type mice. Infection with C albicans induced high titres of anti-C albicans mannan IgM and IgG in MBL-deficient mice but only a modest and transient IgM response with no class switch to IgG in wild type mice. Cross-reactive ASCA IgM continuously increased in MBL-deficient mice but rapidly declined after transient induction in wild type mice. In MBL-deficient mice, increased C albicans dissemination correlated with reduced early retention in the circulation.
These results suggest that systemic MBL helps to prevent excessive inflammation upon access of normally mild pathogens across the damaged intestinal epithelium. Lack of this innate defence promotes antibody responses with cross-reactive potential against common mannan epitopes. These interpretations are compatible with the increased prevalence of ASCA and complicated disease phenotypes in MBL-deficient patients with CD.
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