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991.
Przemysaw Soek Jennifer Mytych Anna Tabcka-onczyska Marek Koziorowski 《International journal of molecular sciences》2021,22(21)
The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples. 相似文献
992.
Marta Kaszowska Grazyna Majkowska-Skrobek Pawel Markwitz Cdric Lood Wojciech Jachymek Anna Maciejewska Jolanta Lukasiewicz Zuzanna Drulis-Kawa 《International journal of molecular sciences》2021,22(21)
Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting K. pneumoniae against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on K. pneumoniae virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from Klebsiella siphovirus KP36 was used as the selective agent during the treatment of K. pneumoniae 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the wbaP gene located within the cps gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response. 相似文献
993.
Radhika Kapoor Christina Anna Stratopoulou Marie-Madeleine Dolmans 《International journal of molecular sciences》2021,22(21)
Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2–10% of women experience this condition during reproductive age, 35–50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis. 相似文献
994.
Anna Zita Mehira Kamptner Christoph-Erik Mayer Hedwig Sutterlüty 《International journal of molecular sciences》2021,22(21)
Sprouty proteins are widely accepted modulators of receptor tyrosine kinase-associated pathways and fulfill diversified roles in cancerogenesis dependent on the originating cells. In this study we detected a high expression of Sprouty3 in osteosarcoma-derived cells and addressed the question of whether Sprouty3 and Sprouty1 influence the malignant phenotype of this bone tumor entity. By using adenoviruses, the Sprouty proteins were expressed in two different cell lines and their influence on cellular behavior was assessed. Growth curve analyses and Scratch assays revealed that Sprouty3 accelerates cell proliferation and migration. Additionally, more colonies were grown in Soft agar if the cells express Sprouty3. In parallel, Sprouty1 had no significant effect on the measured endpoints of the study in osteosarcoma-derived cells. The promotion of the tumorigenic capacities in the presence of Sprouty3 coincided with an increased activation of signaling as measured by evaluating the phosphorylation of extracellular signal-regulated kinases (ERKs). Ectopic expression of a mutated Sprouty3 protein, in which the tyrosine necessary for its activation was substituted, resulted in inhibited migration of the treated cells. Our findings identify Sprouty3 as a candidate for a tumor promoter in osteosarcoma. 相似文献
995.
Karen Trchounian Anna Poladyan Armen Trchounian 《International Journal of Hydrogen Energy》2017,42(10):6590-6597
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. 相似文献
996.
Karen Trchounian Satenik Mirzoyan Anna Poladyan Armen Trchounian 《International Journal of Hydrogen Energy》2017,42(38):24026-24034
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. 相似文献
997.
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 相似文献
998.
Bernard Martel Philippe Le Thuaut Gregorio Crini Michel Morcellet Anna‐Maria Naggi Ulrich Maschke Sabrina Bertini Carmen Vecchi Xavier Coqueret Giangiacomo Torri 《应用聚合物科学杂志》2000,78(12):2166-2173
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 相似文献
999.
Tomasz Jan Kolanowski Weronika Wargocka-Matuszewska Agnieszka Zimna Lukasz Cheda Joanna Zyprych-Walczak Anna Rugowska Monika Drabik Micha Fiedorowicz Seweryn Krajewski ukasz Steczek Cezary Kozanecki Zbigniew Rogulski Natalia Rozwadowska Maciej Kurpisz 《International journal of molecular sciences》2021,22(22)
1000.
Anna Pierzchliska Marek Dro
dzik Monika Biaecka 《International journal of molecular sciences》2021,22(22)
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. 相似文献