Optimiranje podloge za proizvodnju celulaze s pomoću mutiranog soja Trichoderma reesei WX-112 metodom odzivnih površina

The mutant strain Trichoderma reesei WX-112 with high cellulase activity was isolated by a newly invented plate. The mutant’s ability to produce cellulase increased 1.95 times after the treatment with UV and N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Also, the medium composition was optimized using response surface methodology (RSM). A fractional factorial design (26–2) was applied to elucidate the medium components that significantly affect cellulase production. The concentration of Avicel and soybean cake flour in the medium were significant factors. The steepest ascent method was used to locate the optimal domain and a central composite design was used to estimate the quadratic response surface from which the factor levels for maximum production of cellulase were determined. The composition of fermentation medium optimized with response surface methodology was (in g/L): wheat bran 30, Avicel 36.4, soybean cake flour 24.7, KH2PO4 4 and corn steep flour 5. Compared to the original medium, the cellulase activity increased from 7.2 to 10.6 IU/mL.Mutirani soj Trichoderma reesei WX-112, velike celulazne aktivnosti, izoliran je na tek izumljenoj ploši za uzgoj. Sposobnost mutiranoga soja da proizvodi celulazu povečala se 1,95 puta nakon obrade UV-zračenjem i N-metil-N’-nitro-N nitrozogvanidinom (MNNG). Sastav podloge optimiran je metodom odzivnih površina. Reducirani faktorski plan (26–2) primijenjen je kako bi se objasnio značajan utjecaj komponenata na proizvodnju celulaze, a osobito koncentracija Avicela i odmašćenog sojinog brašna u podlozi. Metodom najstrmijeg uspona utvrđeno je optimalno područje, a centralno uređenim planom određena je kvadratna odzivna površina prema kojoj se vide razine faktora za maksimalnu proizvodnju celulaze. Podloga optimirana metodom odzivnih površina sadržavala je 30 g/L pšeničnih mekinja, 36,4 g/L Avicela, 24,7 g/L odmašćenog sojinog brašna, 4 g/L KH2PO4 i 5 g/L kukuruzne mokre meljave. U usporedbi s početnom podlogom celulazna se aktivnost povećala od 7,2 na 10,6 IU/m

Anderson Localization and Mobility Edge in Curved Spacetime

We construct a quasiperiodic lattice model in a curved spacetime to explore the crossover concerning both condensed matter and curved spacetime physics. We study the related Anderson localization and find that the model has a clear boundary of localized-extended phase separation, which leads to the mobility edge, i.e., the coexistence of nonergodic localized, critical and extended phases. A novel self-consistent segmentation method is developed to calculate the analytical expression of the critical position of phase separation, and the rich phase diagram is determined by calculating the fractal dimension and scaling index in multifractal analysis.Comment: 17 pages, 4+12 figure

ER stress: an emerging regulator in GVHD development

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematologic malignancies. However, the clinical benefits of allo-HCT are limited by the development of complications including graft-versus-host disease (GVHD). Conditioning regimens, such as chemotherapy and irradiation, which are administered to the patients prior to allo-HCT, can disrupt the endoplasmic reticulum (ER) homeostasis, and induce ER stress in the recipient’s cells. The conditioning regimen activates antigen-presenting cells (APCs), which, in turn, activate donor cells, leading to ER stress in the transplanted cells. The unfolded protein response (UPR) is an evolutionarily conserved signaling pathway that manages ER stress in response to cellular stress. UPR has been identified as a significant regulatory player that influences the function of various immune cells, including T cells, B cells, macrophages, and dendritic cells (DCs), in various disease progressions. Therefore, targeting the UPR pathway has garnered significant attention as a promising approach for the treatment of numerous diseases, such as cancer, neurodegeneration, diabetes, and inflammatory diseases. In this review, we summarize the current literature regarding the contribution of ER stress response to the development of GVHD in both hematopoietic and non-hematopoietic cells. Additionally, we explore the potential therapeutic implications of targeting UPR to enhance the effectiveness of allo-HCT for patients with hematopoietic malignancies

LBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice

Histone deacetylase inhibitors (HDACis) are a new class of compounds that induce acetylation of histone lysine tails in chromatin and modify gene expression. The Food & Drug Administration approved HDACi, Vorinostat, or suberoylanilide hydroxamic acid (SAHA), has been shown to inhibit tumor cell growth and the production of proinflammatory cytokines. In preclinical allogeneic transplant models, SAHA induces graft-versus-host disease (GVHD) amelioration in treated mice without impairing graft-versus-leukemia. LBH589 (Panobinostat), a structurally novel cinnamic hydroxamic acid class, is an HDACi more potent than SAHA. In the current work, we tested the hypothesis that LBH589 would be highly effective in the prevention of GVHD. Using mouse model of allogeneic bone marrow transplant (BMT), we unexpectedly found that treatment with LBH589 accelerated GVHD, in contrast to the treatment with SAHA that alleviated GVHD. Accelerated GVHD in the recipients treated with LBH589 was associated with elevated Th1 cytokines in recipient serum, enhanced CXCR3 expression on donor T cells, and T cell infiltration in the liver. The current study highlights the distinct effects of pan HDACi on allogeneic BMT and alerts that LBH589 (Panobinostat) could have an adverse effect on GVHD, and possibly on other inflammatory diseases

Paeoniflorin inhibits the growth of bladder carcinoma via deactivation of STAT3

Bladder cancer (BCa) is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae) can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis) synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway