Enhancement of Escherichia coli bacterial biomass and hydrogen production by some heavy metal ions and their mixtures during glycerol vs glucose fermentation at a relatively wide range of pH

Escherichia coli growth and H₂ production were followed in the presence of heavy metal ions and their mixtures during glycerol or glucose fermentation at pH 5.5–7.5. Ni²⁺ (50 μM) with Fe²⁺ (50 μM) but not sole metals stimulated bacterial biomass during glycerol fermentation at pH 6.5. Ni²⁺+Fe³⁺ (50 μM), Ni² +Fe³⁺+Mo⁶⁺ (20 μM) and Fe³⁺+Mo⁶⁺ (20 μM) but not sole metals enhanced up to 3-fold H₂ yield but Cu⁺ or Cu²⁺ (100 μM) inhibited it. At pH 7.5 stimulating effect on biomass was observed by Ni²⁺+Fe²⁺+Mo⁶⁺. H₂ production was enhanced 2.7 fold particularly by Ni²⁺+Fe³⁺+Mo⁶⁺ at the late stationary growth phase. Whereas at pH 5.5 increased biomass was when Fe²⁺+Mo⁶⁺ or Mo⁶⁺ were added. H₂ yield was decreased compared with that at pH 6.5, but metal ions again enhanced it. During glucose fermentation at pH 6.5 biomass was increased by the mixtures of metal ions, and 1.2 fold increased H₂ yield was observed. At pH 7.5 Ni²⁺+Fe²⁺ increased biomass but Cu⁺ or Cu²⁺ had suppressing effect; Fe³⁺+Mo⁶⁺ stimulated H₂ production. At pH 5.5 biomass also was raised by Ni²⁺+Fe²⁺+Mo⁶⁺; H₂ yield was increased upon Mo⁶⁺ and Mo⁶⁺+Fe²⁺ or Mo⁶⁺+Fe³⁺ additions. The results point out the importance of Ni²⁺, Fe²⁺, Fe³⁺ and Mo⁶⁺ and some of their combinations for E. coli bacterial growth and H₂ production mostly during glycerol but not glucose fermentation and at acidic conditions (pH 5.5 and 6.5). They can be used for optimizing fermentation processes on glycerol, controlling bacterial biomass and developing H₂ production biotechnology.     

Hydrogen production by Escherichia coli growing in different nutrient media with glycerol: Effects of formate,pH, production kinetics and hydrogenases involved

The Escherichia coli BW25113 or MC4100 wild type parental strains growth and H₂ production kinetics was studied in batch cultures of minimal salt medium (MSM) and peptone medium (PM) at pH of 5.5–7.5 upon glycerol (10 g L^?1) fermentation and formate (0.68 g L^?1) supplementation. The role of formate alone or with glycerol on growth and H₂ production via hydrogenases (Hyd) was investigated in double hyaB hybC (lacking large subunits of Hyd 1 and 2), triple hyaB hybC hycE (lacking large subunits of Hyds 1-3) and sole selC (lacking formate dehydrogenase H) mutants during 24 h bacterial growth. H₂ production was delayed and observed after 24 h bacterial wild type strains growth on MSM. Moreover, it reached the maximal values after 72 h growth at the pH 6.5 and pH 7.5. Biomass formation of the mutants used was inhibited ～3.5 fold compared with wild type, and H₂ production was absent in hyaB hybC hycE and selC mutants upon glycerol utilization on MSM at pHs of 5.5–7.5. Formate inhibited bacterial growth on MSM with glycerol, but enhanced and recovered H₂ production by hybC mutant at pH 7.5. H₂ evolution was delayed at pH 7.5 in PM, but observed and stimulated at pH 6.5 upon glycerol and formate utilization in hyaB hybC mutant. H₂ production was absent in hyaB hybC hycE and selC mutants upon glycerol, formate alone or with glycerol fermentation at pH 6.5 and pH 7.5; formate supplementation had no effect. The results point out E. coli ability to grow and utilize glycerol in MSM with comparably high H₂ yield: as well as they suggest the key role of Hyd-3 at both pH 6.5 and pH 7.5 and the role of Hyd-2 and Hyd-4 at pH 7.5 in H₂ production by E. coli during glycerol fermentation with formate supplementation. The results obtained are novel and might be useful in H₂ production biotechnology development using different nutrient media and glycerol and formate as feedstock.     

Water‐sorption behavior of P‐phenylene diamine–based polyimide thin films

Four different p‐PDA–based polyimide thin films were prepared from their respective poly(amic acid)s through thermal imidization at 400°C: poly(p‐phenylene pyromellitimide) (PMDA‐PDA); poly(p‐phenylene biphenyltetra carboximide) (BPDA‐PDA); poly(p‐phenylene 3,3′,4,4′‐oxydiphthalimide) (ODPA‐PDA); and poly(p‐phenylene 4,4′‐hexafluoroisopropylidene diphthalimide) (6FDA‐PDA). Water‐sorption behaviors of polyimide films were gravimetrically investigated at 25°C and 22–100% relative humidity by using the modified electromicrobalance (Thin Film Diffusion Analyzer). The diffusion coefficients of water for the polyimides varies in the range of 1.6 to 10.5 × 10⁻¹⁰ cm²/s, and are in the increasing order: BPDA‐PDA < PMDA‐PDA ∼ ODPA‐PDA < 6FDA‐PDA. The water uptakes of polyimides vary from 1.46 to 5.80 wt %, and are in the increasing order: BPDA‐PDA < ODPA‐PDA < 6FDA‐PDA < PMDA‐PDA. The water‐sorption behaviors for the p‐PDA–based polyimides are closely related to the morphological structure; specifically, the diffusion coefficients in p‐PDA–based polyimide thin films are closely related to the in‐plane orientation and mean intermolecular distance, whereas the water uptakes are affected by the packing order. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1315–1323, 2000     

Grafting of cyclodextrins onto polypropylene nonwoven fabrics for the manufacture of reactive filters. II. Characterization

A novel method for the preparation of immobilized α, β, or γ‐cyclodextrins on polypropylene nonwoven supports has been previously presented. The obtained new materials were prepared by graft‐polymerization of glycidyl methacrylate onto polypropylene after activation of the support by the electron beam technique, followed by the coupling of cyclodextrins with the epoxide groups. The structure of the resulting materials is characterized in detail using Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance analysis, differential scanning calorimetry, thermogravimetric analysis, and optical microscopy. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 2166–2173, 2000     

A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors—statins—via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene’s genetic variability.     

Dendritic Cells and Cancer Immunotherapy: The Adjuvant Effect

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.     

Tau Cleavage Contributes to Cognitive Dysfunction in Strepto-Zotocin-Induced Sporadic Alzheimer’s Disease (sAD) Mouse Model

Tau cleavage plays a crucial role in the onset and progression of Alzheimer’s Disease (AD), a widespread neurodegenerative disease whose incidence is expected to increase in the next years. While genetic and familial forms of AD (fAD) occurring early in life represent less than 1%, the sporadic and late-onset ones (sAD) are the most common, with ageing being an important risk factor. Intracerebroventricular (ICV) infusion of streptozotocin (STZ)—a compound used in the systemic induction of diabetes due to its ability to damage the pancreatic β cells and to induce insulin resistance—mimics in rodents several behavioral, molecular and histopathological hallmarks of sAD, including memory/learning disturbance, amyloid-β (Aβ) accumulation, tau hyperphosphorylation, oxidative stress and brain glucose hypometabolism. We have demonstrated that pathological truncation of tau at its N-terminal domain occurs into hippocampi from two well-established transgenic lines of fAD animal models, such as Tg2576 and 3xTg mice, and that it’s in vivo neutralization via intravenous (i.v.) administration of the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) is strongly neuroprotective. Here, we report the therapeutic efficacy of 12A12mAb in STZ-infused mice after 14 days (short-term immunization, STIR) and 21 days (long-term immunization regimen, LTIR) of i.v. delivery. A virtually complete recovery was detected after three weeks of 12A12mAb immunization in both novel object recognition test (NORT) and object place recognition task (OPRT). Consistently, three weeks of this immunization regimen relieved in hippocampi from ICV-STZ mice the AD-like up-regulation of amyloid precursor protein (APP), the tau hyperphosphorylation and neuroinflammation, likely due to modulation of the PI3K/AKT/GSK3-β axis and the AMP-activated protein kinase (AMPK) activities. Cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations occurring in STZ-infused mice were also strongly attenuated by 12A12mAb delivery. These results further strengthen the causal role of N-terminal tau cleavage in AD pathogenesis and indicate that its specific neutralization by non-invasive administration of 12A12mAb can be a therapeutic option for both fAD and sAD patients, as well as for those showing type 2 diabetes as a comorbidity.     

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC₅₀=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.     

Assessing the antiproliferative effect of biogenic silver chloride nanoparticles on glioblastoma cell lines by quantitative image‐based analysis

Glioblastoma is the most life‐threatening tumour of the central nervous system. Temozolomide (TMZ) is the first‐choice oral drug for the treatment of glioblastoma, although it shows low efficacy. Silver nanoparticles (AgNPs) have been shown to exhibit biocidal activity in a variety of microorganisms, including some pathogenic microorganisms. Herein, the antiproliferative effect of AgCl‐NPs on glioblastoma cell lines (GBM02 and GBM11) and on astrocytes was evaluated through automated quantitative image‐based analysis (HCA) of the cells. The cells were treated with 0.1‐5.0 μg/ml AgCl‐NPs or with 9.7‐48.5 μg/ml TMZ. Cells that received combined treatment were also analysed. At a maximum tested concentration of AgCl‐NPs, GBM02 and GBM11, the growth decreased by 93% and 40%, respectively, following 72 h of treatment. TMZ treatment decreased the proliferation of GBM02 and GBM11 cells by 58% and 34%, respectively. Combinations of AgCl‐NPs and TMZ showed intermediate antiproliferative effects; the lowest concentrations caused an inhibition similar to that obtained with TMZ, and the highest concentrations caused inhibition similar to that obtained with AgCl‐NPs alone. No significant changes in astrocyte proliferation were observed. The authors’ findings showed that HCA is a fast and reliable approach that can be used to evaluate the antiproliferative effect of the nanoparticles at the single‐cell level and that AgCl‐NPs are promising agents for glioblastoma treatment.