Turkish journal of biology = Turk biyoloji dergisi最新文献

Neurodegeneration is the progressive loss of structure or function of neurons. Amyloid beta oligomers and aggregates have been linked to neurodegeneration. While previous studies have suggested that dietary α-tocopherol intake can prevent amyloid beta aggregation and protect the brain against neurotoxicity, other research, however, indicated that tocotrienol forms might be used as an alternate agent against this kind of degeneration. In the presented research, we compared the in vitro protective effects of α-tocopherol and α-tocotrienol. In this context, we formed an in vitro neurodegeneration model with primary isolated neurons and measured α-tocopherol's and α-tocotrienol's protective effects. As a result, α-tocopherol and α-tocotrienol prevent the degeneration of neurons. Moreover, α-tocopherol and α-tocotrienol regulated the neuron's calcium channels mechanism by decreasing the expression of the calcium channel alpha 1C subunit. We also observed that the amount of amyloid beta accumulation in the extracellular matrix decreased with the application of these isoforms. In specific time points, α-tocopherol and α-tocotrienol differ in terms of protective effects. In conclusion, it could be interpreted that, in more extended periods, α-tocotrienol could be a significant protective agent against amyloid beta-induced neurodegeneration, and it can be used as an alternative to other protective agents, especially α-tocopherol.

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were transfected and compared to negative control siRNAs. We determined mRNA levels in autophagy, invasion, and apoptosis genes with the combination of reverse transcription-polymerase chain reaction (RT-PCR) and western blotting in PC3 cell lines after STMN1 silencing. It was determined that STMN1 was overexpressed significantly in PCa cases, immunohistochemically. The overexpression of STMN1 was significantly correlated with the high-grade Gleason score, and it was associated with a worse prognosis of PCa cases according to the Kaplan-Meier survival analysis (p < 0.05). Significant silencing in STMN1 was determined (87.5%) after siRNA applications. Especially, invasion genes such as claudin 7, fibroblast growth factor 8, hypoxia-inducible factor 1 subunit alpha, hepatocyte growth factor, matrix metallopeptidase 2, 7 genes, markedly, decreased by siRNA-mediated STMN1silencing. STMN1 silencing was determined to significantly increase caspase 3 protein expression by using western blot analysis (p < 0.001). Although STMN1 silencing did not have a significant effect on the induction of apoptosis and autophagy-related genes in PCa cells, it was shown to affect apoptotic mechanisms through the caps3 protein. siRNA-mediated STMN1 silencing decreases proliferation in the PCa cell line. It is thought that STMN1 can serve as a potential therapeutic target in the advanced stage-PCa, especially.

The selection of a wound dressing is crucial for successful wound management. Conventional dressings are preferable for the treatment of simple wounds. However, a bioactive wound dressing that supports wound management and accelerates the healing process is required when it comes to treating non-self-healing wounds. 2-deoxy-D-ribose (2dDR) is a small deoxy sugar that naturally occurs in human body. Although we have previously demonstrated that 2dDR can be used to induce neovascularisation and accelerates wound healing in vitro and in vivo, the literature on small sugars is conflicting, and the knowledge on how 2dDR achieves its biological activity is very limited. In this study, several small sugars including D-glucose (DG), 2-deoxy-D-glucose (2dDG), 2deoxy-L-ribose (2dLR) were compared to 2dDR by investigating their effects on the metabolic activities of both human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts (HDFs). Then, for the first time, a two-dimensional (2D) scratch wound healing model was used to explore the migratory response of HDFs in response to 2dDR treatment. Finally, 2dDR was incorporated into Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) polymer fibres via electrospinning, and the metabolic activity of both types of cells in vitro was investigated in response to sugar release via Alamar Blue assay. The results demonstrated that 2dDR was the only sugar, among others, that enhances the metabolic activity of both HDMECs and HDFs and the migratory response of HDFs in a 2D scratch assay in a dose-dependent manner. In addition to direct administration, 2dDR was also found to increase the metabolic activity of HDMECs and HDFs over 7 days when released from polymer fibres. It is concluded that 2dDR is a potential pro-angiogenic agent that has a positive impact not only on endothelial cells but also fibroblasts, which take a key role in wound healing. It could easily be introduced into polymeric scaffolds to be released quickly to enhance the metabolic activity and the migratory response of cells that are associated with angiogenesis and wound healing.

Coronavirus disease 2019 (COVID-19) pandemic has been an important global interest that affected millions of people, and it requires a deep investigation of the disease immunology for developing further therapeutic applications. Adoptive T cell therapy promises to address T cell-dependent immune dysregulation in COVID-19 patients by the generation of specific T cell clones against virus-specific antigens. Additionally, targeting B cell-dependent protection through COVID-19 vaccines, which have been developed in the recent year, possessed sufficient prevention for spreading the virus, since the cases and deaths related to COVID-19 tend to decrease after the vaccination. However, adoptive cell therapies are now encouraging scientists to deal with pathological challenges like inadequate T cell-dependent immune response or lymphopenia, since they are the most frequent outcome of severe infection, especially in immunocompromized patients. In this review, the current knowledge of immunopathology of COVID-19 was aimed to be highlighted along with the T cell responses against SARS-CoV-2 to comprise a basis for therapeutics. Moreover, current therapeutics and treatment strategies for COVID-19 were discussed to evaluate possible agents. Furthermore, the use of adoptive T cell therapy representing an emerging therapeutic approach was purposed to be presented comprehensively against SARS-CoV-2 infection. Even though further studies are needed to fully understand T cell response against SARS-CoV-2 in order to develop therapies to provide long term and efficient protection, adoptive cell therapies now meet the demand for a large population of people who suffer immunocompromization, considering the previous usage of the technique for different infectious diseases.

Around 200 different lipopeptides (LPs) have been identified to date, most of which are produced via Bacillus and Pseudomonas species. The clinical nature of the lipopeptide (LP) has led to a big surge in its research. They show antimicrobial and antitumor activities due to which mass-scale production and purification of LPs are beneficial. Response surface methodology (RSM) approach has emerged as an alternative in the field of computational biology for optimizing the reaction parameters using statistical models. In the present study, Pseudomonas sp. strain OXDC12 was used for production and partial purification of LPs using Thin Layer Chromatography (TLC). The main goal of the study was to increase the overall yield of LPs by optimizing the different variables in the fermentation broth. This was achieved using a combination of one factor at a time (OFAT) and response surface methodology (RSM) approaches. OFAT technique was used to optimize the necessary parameters and was followed by the creation of statistical models (RSM) to optimize the remaining variables. Maximum mycelial growth inhibition (%) against the fungus Mucor sp. was 61.3% for LP. Overall, the combination of both OFAT and RSM helped in increasing the LPs yield by 3 folds from 367mg/L to 1169mg/L.

Prevascularization and mechanical stimulation have been reported as effective methods for the construction of functional bone tissue. However, their combined effects on osteogenic differentiation and its mechanism remain to be explored. Here, the effects of fluid shear stress (FSS) on osteogenic differentiation of rat bone-marrow-derived mesenchymal stem cells (BMSCs) when cocultured with human umbilical vein endothelial cells (HUVECs) were investigated, and underlying signaling mechanisms were further explored. FSS stimulation for 1-4 h/day increased alkaline phosphatase (ALP) activity and calcium deposition in coculture systems and promoted the proliferation of cocultured cells. FSS stimulation for 2 h/day was selected as the optimized protocol according to osteogenesis in the coculture. In this situation, the mRNA levels of ALP, runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and protein levels of OCN and osteopontin (OPN) in BMSCs were upregulated. Furthermore, FSS and coculture with HUVECs synergistically increased integrin β1 expression in BMSCs and further activated focal adhesion kinases (FAKs) and downstream extracellular signal-related kinase (ERK), leading to the enhancement of Runx2 expression. Blocking the phosphorylation of FAK abrogated FSS-induced ERK phosphorylation and inhibited osteogenesis of cocultured BMSCs. These results revealed that FSS and coculture with HUVECs synergistically promotes the osteogenesis of BMSCs, which was mediated by the integrin β1-FAK-ERK signaling pathway.

Gelatinases A and B, which are members of the matrix metalloproteinase (MMP) family, play essential roles in cancer development and metastasis, as they can break down basal membranes. Therefore, the determination and inhibition of gelatinases is essential for cancer treatment. Peptides that can specifically block each gelatinase may, therefore, be useful for cancer treatment. In this study, subtractive panning was carried out using a 12-mer peptide library to identify peptides that block gelatinase A activity (MMP-2), which is a key pharmacological target. Using this method, 17 unique peptide sequences were determined. MMP-2 inhibition by these peptides was evaluated through zymogram analyses, which revealed that four peptides inhibited MMP-2 activity by at least 65%. These four peptides were synthesized and used for in vitro wound healing using human umbilical vein endothelial cells, and two peptides, AOMP12 and AOMP29, were found to inhibit wound healing by 40%. These peptides are, thus, potential candidates for MMP-2 inhibition for cancer treatment. Furthermore, our findings suggest that our substractive biopanning screening method is a suitable strategy for identifying peptides that selectively inhibit MMP-2.

Bladder cancer is one of the most frequent cancers and causes more than 150.000 deaths each year. During the last decade, several studies provided important aspects about genomic characterization, consensus subgroup definition, and transcriptional regulation of bladder cancer. Still, much more research needs to be done to characterize molecular signatures of this cancer in depth. At this point, the use of bladder cancer cell lines is quite useful for the identification and test of new signatures. In this study, we classified the bladder cancer cell lines according to the activities of regulons implicated in the regulation of primary bladder tumors. Our regulon gene expression-based classification revealed three groups, neuronal-basal (NB), luminal-papillary (LP), and basal-squamous (BS). These regulon gene expression-based classifications showed a quite good concordance with the consensus subgroups assigned by the primary bladder cancer classifier. Importantly, we identified FGFR1 regulon to be involved in the characterization of the NB group, where neuroendocrine signature genes were significantly upregulated, and further β-catenin was shown to have significantly higher nuclear localization. LP groups were mainly driven by the regulons ERBB2, FOXA1, GATA3, and PPARG, and they showed upregulation of the genes involved in epithelial differentiation and urogenital development, while the activity of EGFR, FOXM1, STAT3, and HIF1A was implicated for the regulation of BS group. Collectively, our results and classifications may serve as an important guide for the selection and use of bladder cancer cell lines for experimental strategies, which aim to manipulate regulons critical for bladder cancer development.

It has been a long time since researchers have focused on the cytoskeletal proteins' unconventional functions in the nucleus. Subcellular localization of a protein not only affects its functions but also determines the accessibility for cellular processes. Desmin is a muscle-specific, cytoplasmic intermediate filament protein, the cytoplasmic roles of which are defined. Yet, there is some evidence pointing out nuclear functions for desmin. In silico and wet lab analysis shows that desmin can enter and function in the nucleus. Furthermore, the candidate nuclear partners of desmin support the notion that desmin can serve as a transcriptional regulator inside the nucleus. Uncovering the nuclear functions and partners of desmin will provide a new insight into the biological significance of desmin.

Phylogenetic trees are useful tools to infer evolutionary relationships between genetic entities. Phylogenetics enables not only evolution-based gene clustering but also the assignment of gene duplication and deletion events to the nodes when coupled with statistical approaches such as bootstrapping. However, extensive gene duplication and deletion events bring along a challenge in interpreting phylogenetic trees and require manual inference. In particular, there has been no robust method of determining whether one of the paralog clades systematically shows higher divergence following the gene duplication event as a sign of functional divergence. Here, we provide Phylostat, a graphical user interface that enables clade divergence analysis, visually and statistically. Phylostat is a web-based tool built on phylo.io to allow comparative clade divergence analysis, which is available at https://phylostat.adebalilab.org under an MIT open-source licence.