On a long, narrow road: The mental health law in Turkey.

This article presents the historical transformation of the mental health system and policies in the case of Turkey and discusses the challenges to their effective implementation. The mental health system in Turkey has undergone a series of reforms in three periods, namely, the institutionalization of psychiatry and hospital-based mental health services in the mid-19th century, the introduction of first-generation community-based mental healthcare services in the 1960s, and the policy of deinstitutionalization after the 1980s. In this transformation process, certain initiatives have been implemented with the participation of interested actors across periods and small but important improvements.

BML-260 promotes the growth of cord blood and mobilized peripheral blood hematopoietic stem and progenitor cells with improved reconstitution ability.

Hematopoietic stem cells (HSCs), which are multipotent and have the ability to self-renew, are frequently used in the treatment of hematological diseases and cancer. Small molecules that target HSC quiescence regulators could be used for ex vivo expansion of both mobilized peripheral blood (mPB) and umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HSPC). We identified and investigated 35 small molecules that target HSC quiescence factors.

Competitive inhibition of IL-2/IL-2R has a dual effect on HSC ex vivo expansion and IL-2R (CD25) content.

Interleukin-2 (IL-2) and its receptor play a pivotal role in the regulation of immune response and possess both immune-regulatory and immune-stimulatory functions. As a cytokine of lymphoid cells, the role of IL-2 has been revealed in hematopoietic stem cell (HSC) maintenance and proper hematopoiesis. Here, we investigated that small molecule Ro 26-4550 trifluoroacetate (Ro) mediated competitive inhibition of IL-2 and its receptor alpha subunit (IL-2Rα) throughout ex vivo culture.

Development of a novel and synthetic HematoMiR technology that broadly modulates quiescence of stem cells and enhances HSC expansion.

Hematopoietic stem cell (HSCs) transplantation is the primary therapeutic modality used to treat hematopoietic disorders. It centers on the capability of a small quantity of HSCs to repopulate whole blood lineages. Along with limited availability of suitable donors, the need for sufficient number of donor HSCs is still challenging in clinical relevance.

The current state of validated small molecules inhibiting SARS-CoV-2 nonstructural proteins.

The current COVID-19 outbreak has had a profound influence on public health and daily life. Despite all restrictions and vaccination programs, COVID-19 still can lead to fatality due to a lack of COVID-19-specific treatments. A number of studies have demonstrated the feasibility to develop therapeutics by targeting underlying components of the viral proteome.

Lead Optimization and Structure-Activity Relationship Studies on Myeloid Ecotropic Viral Integration Site 1 Inhibitor.

The pivotal role of the myeloid ecotropic viral integration site 1 (MEIS1) transcriptional factor was reported in cardiac regeneration and hematopoietic stem-cell (HSC) regulation with our previous findings. MEIS1 as a promising target in the context of pharmacological inhibition, we identified a potent myeloid ecotropic viral integration site (MEIS) inhibitor, MEISi-1, to induce murine and human HSC expansion and . In this work, we performed lead optimization on MEISi-1 by synthesizing 45 novel analogues.

Modulating Cas9 activity for precision gene editing.

The CRISPR/Cas9 is a RNA-guided nuclease complex that can be specifically programmed to target a user-specified DNA sequence. It has been a powerful and effective tool of genome editing. However, off-target activity of the Cas9 nuclease limits its potential use in the correction of inherited diseases and bona fide gene editing.

Small molecule-mediated modulation of ubiquitination and neddylation improves HSC function ex vivo.

Hematopoietic stem cells (HSCs) are particularly characterized by their quiescence and self-renewal. Cell cycle regulators tightly control quiescence and self-renewal capacity. Studies suggest that modulation of ubiquitination and neddylation could contribute to HSC function via cyclin-dependent kinase inhibitors (CDKIs).

Cloning, expression and characterization of recombinant CagA protein of Helicobacter pylori using monoclonal antibodies: Its potential in diagnostics.

Helicobacter pylori CagA protein plays an important role in the severity of the gastric diseases. Our aims were to clone the cagA 5'- conserved region of the gene, characterize the recombinant CagA (rCagA) protein by monoclonal antibodies (mAbs) and to use this protein for the detection of anti-CagA antibodies by an ELISA test. Our developed rCagA protein (67 kDa) showed an amino acid sequence homology of 83% and 80% with Western and East Asian type strains respectively.

Development of small-molecule-induced fibroblast expansion technologies.

Dermal fibroblasts are responsible from the production of extracellular matrix and take role in the closure of skin wounds. Dermal fibroblasts are major cells of origin in the generation of induced pluripotent stem cells (IPSCs) and are historically being used as feeder layer and biofiller in the restorative surgeries. ex vivo expansion of the dermal fibroblasts provides a suitable model to study skin biology and to engineer bioartifical skins.

Development of Small Molecule MEIS Inhibitors that modulate HSC activity.

Meis1, which belongs to TALE-type class of homeobox gene family, appeared as one of the key regulators of hematopoietic stem cell (HSC) self-renewal and a potential therapeutical target. However, small molecule inhibitors of MEIS1 remained unknown. This led us to develop inhibitors of MEIS1 that could modulate HSC activity.

Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment.

Hematopoietic stem cells (HSCs) are known to reside in a bone marrow (BM) niche, which is associated with relatively higher calcium content. HSCs sense and respond to calcium changes. However, how calcium-sensing components modulate HSC function and expansion is largely unknown.

Developments in Artificial Platelet and Erythroid Transfusion Products.

Platelet and blood transfusions have vital importance to the lives of many patients. Platelet transfusions are a life-saving intervention by reducing risk of bleeding in thrombocytopenic patients. Due to the short shelf life of platelets and their limited availability, researchers have developed various platelet transfusion production technologies.

Evaluation of immobilized metal affinity chromatography kits for the purification of histidine-tagged recombinant CagA protein.

Immobilized metal affinity chromatography (IMAC) technique is used for fast and reliable purification of histidine(His)-tagged recombinant proteins. The technique provides purification under native and denaturing conditions. The aim of this study is to evaluate three commercially available IMAC kits (Thermo Scientific, GE Healthcare and Qiagen) for the purification of a 6xHis-tagged recombinant CagA (cytotoxin-associated gene A) protein from IPTG-induced Escherichia coli BL21(DE3) culture.

Evaluation of the effect of cagPAI genes of Helicobacter pylori on AGS epithelial cell morphology and IL-8 secretion.

Helicobacter pylori cagPAI genes play an important role in pathogenesis, however little is known about their functions in isolates from Turkish patients. We aimed to evaluate the intactness and the effect of the cagPAI genes (cagT, cagM, cagE, cagA) and cagA EPIYA motifs on the AGS morphological changes and IL-8 induction. Of 53 patients 38 were found infected with H.

Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70.

The inducible T cell kinase-spleen tyrosine kinase (ITK-SYK) oncogene consists of the Tec homology-pleckstrin homology domain of ITK and the kinase domain of SYK, and it is believed to be the cause of peripheral T cell lymphoma. We and others have recently demonstrated that this fusion protein is constitutively tyrosine-phosphorylated and is transforming both in vitro and in vivo. To gain a deeper insight into the molecular mechanism(s) underlying its activation and signaling, we mutated a total of eight tyrosines located in the SYK portion of the chimera into either phenylalanine or to the negatively charged glutamic acid.