Basak Aru

@med.yeditepe.edu.tr

Yeditepe University, Faculty of Medicine, Immunology Department
Yeditepe University



                 

https://researchid.co/aru.basak

EDUCATION

2016 – 2021 Gebze Technical University, Institute of Natural and Applied Sciences, Molecular Biology and Genetics Doctorate Program
Thesis Advisor: Prof. Dr. Ayşe Gül Gürek
Thesis co-advisor: Prof. Dr. Gülderen Yanıkkaya Demirel
Thesis Title: Evaluation of Novel Zinc, Indium and Silicon Phthalocyanines' Anti-Cancer Properties

2013 – 2016 Yeditepe University, Institute of Health Sciences, Molecular Medicine Master Program
Thesis Advisor: Prof. Dr. Gülderen Yanıkkaya Demirel
Thesis Title: Effect of Testosterone Propionate on Bone Marrow Derived Mesenchymal Stem Cells’ Proliferation and Viability

2009 – 2013 İstanbul University, Faculty of Science, Biology Department
Division of Molecular and Cellular Biology

RESEARCH, TEACHING, or OTHER INTERESTS

Multidisciplinary, Immunology, Cancer Research, General Biochemistry, Genetics and Molecular Biology

30

Scopus Publications

Scopus Publications

  • Relationship between immune checkpoint proteins and neoadjuvant chemotherapy response in breast cancer
    Umut Kina Kilicaslan, Basak Aru, Sibel Aydin Aksu, Fugen Vardar Aker, Gulderen Yanikkaya Demirel, and Meryem Gunay Gurleyik

    Elsevier BV

  • Could we use PD-1 and PD-L1 expression on lymphocytes and monocytes as predictive markers for prognosis of acute biliary pancreatitis?
    Ufuk Oguz Idiz, Basak Aru, Cemal Kaya, Kivanc Derya Peker, Cihad Tatar, Mert Guler, Abdurrahman Tunay, Gulderen Yanikkaya Demirel, and Ali Osman Gurol

    Elsevier BV

  • Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma
    Zeynep Akbulut, Başak Aru, Furkan Aydın, and Gülderen Yanıkkaya Demirel

    Frontiers Media SA
    Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.

  • Effect of rapamycin treatment in human seminoma TCam-2 cells through inhibition of G1-S transition
    Tugce Onel, Cihan S. Erdogan, Basak Aru, Ecem Yildirim, Gulderen Yanikkaya Demirel, and Aylin Yaba

    Springer Science and Business Media LLC

  • Secondary metabolites from the underground parts of Valeriana sisymbriifolia Vahl. and their in vitro cytotoxic activities
    Murat Erdoğan, Başak Aru, Şeref Tayga Yılmaz, Erdem Yeşilada, Gülderen Yanıkkaya-Demirel, and Hasan Kırmızıbekmez

    Elsevier BV

  • A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia
    Başak Aru, Cemil Pehlivanoğlu, Zeynep Dal, Nida Nur Dereli-Çalışkan, Ege Gürlü, and Gülderen Yanıkkaya-Demirel

    Frontiers Media SA
    Acute myeloid leukemia (AML) arises from the cells of myeloid lineage and is the most frequent leukemia type in adulthood accounting for about 80% of all cases. The most common treatment strategy for the treatment of AML includes chemotherapy, in rare cases radiotherapy and stem cell and bone marrow transplantation are considered. Immune checkpoint proteins involve in the negative regulation of immune cells, leading to an escape from immune surveillance, in turn, causing failure of tumor cell elimination. Immune checkpoint inhibitors (ICIs) target the negative regulation of the immune cells and support the immune system in terms of anti-tumor immunity. Bone marrow microenvironment (BMM) bears various blood cell lineages and the interactions between these lineages and the noncellular components of BMM are considered important for AML development and progression. Administration of ICIs for the AML treatment may be a promising option by regulating BMM. In this review, we summarize the current treatment options in AML treatment and discuss the possible application of ICIs in AML treatment from the perspective of the regulation of BMM.

  • Immunology of amyotrophic lateral sclerosis – role of the innate and adaptive immunity
    Stefan Mimic, Başak Aru, Cemil Pehlivanoğlu, Hadi Sleiman, Pavle R. Andjus, and Gülderen Yanıkkaya Demirel

    Frontiers Media SA
    This review aims to summarize the latest evidence about the role of innate and adaptive immunity in Amyotrophic Lateral Sclerosis (ALS). ALS is a devastating neurodegenerative disease affecting upper and lower motor neurons, which involves essential cells of the immune system that play a basic role in innate or adaptive immunity, that can be neurotoxic or neuroprotective for neurons. However, distinguishing between the sole neurotoxic or neuroprotective function of certain cells such as astrocytes can be challenging due to intricate nature of these cells, the complexity of the microenvironment and the contextual factors. In this review, in regard to innate immunity we focus on the involvement of monocytes/macrophages, microglia, the complement, NK cells, neutrophils, mast cells, and astrocytes, while regarding adaptive immunity, in addition to humoral immunity the most important features and roles of T and B cells are highlighted, specifically different subsets of CD4+ as well as CD8+ T cells. The role of autoantibodies and cytokines is also discussed in distinct sections of this review.

  • The role of curcumin on apoptosis and NLRP3 inflammasome-dependent pyroptosis on colorectal cancer in vitro
    ZEYNEP DAL and BAŞAK ARU

    The Scientific and Technological Research Council of Turkey (TUBITAK-ULAKBIM) - DIGITAL COMMONS JOURNALS
    . Conclusion: Our results reveal that while curcumin effectively induces apoptosis, its effects on NLRP3-inflammasome mediated pyroptosis vary. Our results underline the need for further research focusing on the other inflammasome complexes to confirm the differential effects of curcumin on CRC.

  • Isolation and characterisation of secondary metabolites from Trifolium vesiculosum Savi and their antiproliferative activities
    Dicle Çevik, Basak Aru, Sanem Karagoz, Niyazi Gurizi, and Ozlem Demirkiran

    Informa UK Limited
    One unreported flavonol namely morin-7-O-methyl ether (1) along with seven known compounds were isolated from the aerial parts of Trifolium vesiculosum Savi which were elucidated by using extensive spectroscopic methods such as 1D and 2D NMR and HR-MS. According to the cell viability assay (MTS) on the purified compounds (1-8), quercetin-3-O-(6''-trans-p-coumaroyl)-β-galactoside (4) revealed remarkable antiproliferative activity most particularly against breast cancer cells (IC50  = 2.90 ± 0.25 µM in HCC1937 and 7.98 ± 0.57 µM in MCF7) while moderate inhibitory activity (IC50  = 17.96 ± 0.51-51.70 ± 2.69 µM) on prostate, colorectal and liver cancer cell viability was observed. Further mechanistic examinations (Annexin V/PI staining, DNA content and detection of reactive oxygen species analyses) showed that compound 4 significantly induced apoptosis, enhanced mitochondrial reactive oxygen species (ROS) accumulation, and caused cell cycle arrest in cancer cells by increasing accumulation of cells at G0/G1 and/or G2/M phases of the cell cycle.

  • Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells while Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy
    Başak Aru, Tuba Akdeniz, Hüsniye Dağdeviren, Gizem Gürel, and Gülderen Yanıkkaya Demirel

    Galenos Yayinevi
    Background: Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells’ cellular responses to testosterone remain unknown. Aims: To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells’ proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell’s polarization and cytotoxicity on K562 leukemia cell line. Study Design: In vitro study. Methods: We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-6-10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells’ cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization. Results: Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10-8 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells’ polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression. Conclusion: The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.

  • Combinatorial effects of melatonin and paclitaxel differ depending on the treatment scheme in colorectal cancer in vitro
    Cihan Suleyman Erdogan, Yasmine Al Hassadi, Basak Aru, Bayram Yılmaz, and Burcu Gemici

    Elsevier BV

  • Activity-Guided Isolation of Cytotoxic Non-Glycosidic Ester Iridoids from Valeriana alliariifolia Adams and Unravelling Their Cell Death Mechanisms
    Murat Erdoğan, Başak Aru, Umut Can Tayğun, Ceren Şimşek, Erdem Yeşilada, Gülderen Yanıkkaya‐Demirel, and Hasan Kırmızıbekmez

    Wiley
    AbstractThe aim of this study was to isolate the cytotoxic compounds from V. alliariifolia via activity‐guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1–11) most of which belong to non‐glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7‐deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4–6 and 8 were found to be the potent cytotoxic compounds (IC50 <10 μM) against at least one of the tested cancer cell lines. Thus, 2, 4–6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4–6 and 8 could be potential anticancer drug leads that deserve further in vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.

  • In vitro cytotoxic activity-guided isolation studies on the underground parts of Valeriana speluncaria Boiss
    Murat Erdoğan, Başak Aru, Ceren Öztürk, Olcay Esin Özdemir, Erdem Yeşilada, Gülderen Yanıkkaya-Demirel, and Hasan Kırmızıbekmez

    Elsevier BV

  • Chemo-photodynamic Activity of Silicon Phthalocyanines Bearing Cyclooxygenase Inhibitors on Colorectal Cancer Cell Lines
    Başak Aru, Gizem Gümüşgöz Çelik, Kevser Harmandar, Belgin Şahin, Ayşe Gül Gürek, Devrim Atilla, and Gülderen Yanıkkaya Demirel

    American Chemical Society (ACS)
    Colorectal cancer ranks as the third most lethal cancer worldwide, resulting in over 1 million cases and 900 000 deaths per year. According to population-based studies, administration of long-term non-steroidal anti-inflammatory drugs (NSAIDs) was proven to reduce the risk of a subject developing colorectal cancer. In the present study, the anti-cancer activity of two different NSAIDs, sulindac- (Pc-1) or diclofenac-substituted (Pc-2) asymmetric silicon phthalocyanine derivatives, was evaluated in four different colorectal cancer cell lines bearing various carcinogenic mutations. In this context, the IC50 values of each compound after 24 and 48 h were determined on HCT116, SW480, LoVo, and HT29 cell lines, and the effects of the compounds on programmed cell death pathways apoptosis and autophagy, their impact on cell cycle progression, and the effect of NSAID moieties they bear on COX-1 and COX-2 proteins were analyzed. In addition, the photophysical and photochemical properties of a synthesized Pc derivative bearing axial diclofenac and triethylene glycol groups (Pc-2) have been investigated, and the compound has been characterized by using different analytical techniques. Our results indicated that both compounds inhibit COX protein expression levels, activate apoptosis in all cell lines, and lead to cell cycle arrest in the G2/M phase, depending on the COX expression profiles of the cell lines, indicating that NSAIDs can be coupled with Pc's to achieve increased anti-cancer activity, especially on cancer cells known to have high COX activity.

  • Comparison of Laboratory Methods for the Clinical Follow Up of Checkpoint Blockade Therapies in Leukemia: Current Status and Challenges Ahead
    Basak Aru, Mojdeh Soltani, Cemil Pehlivanoglu, Ege Gürlü, Mazdak Ganjalikhani-Hakemi, and Gülderen Yanikkaya Demirel

    Frontiers Media SA
    The development of immune checkpoint inhibitors, the monoclonal antibodies that modulate the interaction between immune checkpoint molecules or their ligands on the immune cells or tumor tissue has revolutionized cancer treatment. While there are various studies proving their efficacy in hematological malignancies, there is also a body of accumulating evidence indicating that immune checkpoint inhibitors’ clinical benefits are limited in such diseases. In addition, due to their regulatory nature that balances the immune responses, blockade of immune checkpoints may lead to toxic side effects and autoimmune responses, and even primary or acquired resistance mechanisms may restrict their success. Thus, the need for laboratory biomarkers to identify and monitor patient populations who are more likely respond to this type of therapy and the management of side effects seem critical. However, guidelines regarding the use of immune checkpoint inhibitors in hematological cancers and during follow-up are limited while there is no consensus on the laboratory parameters to be investigated for safety and efficacy of the treatment. This review aims to provide an insight into recent information on predictive and prognostic value of biomarkers and laboratory tests for the clinical follow up of hematological malignancies, with an emphasis on leukemia.

  • Mesenchymal Stem Cells: History, Characteristics and an Overview of Their Therapeutic Administration
    Başak Aru, Gizem Gürel, and Gülderen Yanikkaya Demirel

    Galenos Yayinevi

  • Does LH supplementation in poor responders affect granulosa cells apoptosis rate in ART? A prospective randomised controlled trial
    Sebnem Alanya Tosun, Enis Ozkaya, Basak Aru, Gulderen Yanikkaya Demirel, Ebru Cogendez, and Mehmet Sipahi

    Informa UK Limited
    Abstract The aim was to compare granulosa cell's (GCs) apoptosis rate with (group A) or without (group B) luteinising hormone (LH) supplementation in poor ovarian responders (PORs) during controlled ovarian stimulation (COS). After oocyte retrieval, the follicular fluid was analysed by cytoflowmetry. Primary outcomes were GCs apoptosis rate in terms of viability, early apoptosis, late apoptosis and necrosis. Secondary outcome was clinical pregnancy rate. The viability was 96.7{IQR: 8} and 83.5{IQR: 20} for groups A and B, respectively (p < .001). Late apoptosis rates were significantly lower in group A (median 1.5, {IQR: 3.1}) than group B (median 9.5, {IQR: 20.6}) (p < .001). Median early apoptosis rates were 1.4 {IQR: 2.9} and 5.2 {IQR: 6.5} for group A and B respectively (p = .04). No significant difference was observed in the clinical pregnancy rate. Although LH seems necessary in PORs to decrease late granulosa apoptosis rates, this does not improve clinical pregnancy rates. IMPACT STATEMENT What is already known on this subject? LH supplementation during COS has long been an issue in PORs to overcome the rFSH responsiveness due to the LH polymorphism. LH receptors have also been on GCs and their expression increases in preovulatory follicles. GCs apoptosis rates may show the oocyte quality and reproductive potential of oocyte retrieved and the requirement for LH supplementation. What do the results of this study add? The present study shows that LH supplementation during COS for PORs promotes the GC viability and reduces early/late apoptosis rates. Similarly, the number of MII oocytes was significantly higher in the LH regimen group. However, there was no significant difference in terms of clinical pregnancy rates. What are the implications of these findings for clinical practice and/or further research? The oocyte quality parameters such as higher GC viability and lower GC early/late apoptosis rates verify the LH supplementation in PORs during COS. However, the limited size of this study requires further multi-centre research in a larger cohort of patients. Results obtained with a sensitive and validated method will help clinicians to make better decisions in patient care.

  • Evaluation of histone deacetylase inhibitor substituted zinc and indium phthalocyanines for chemo- And photodynamic therapy
    Başak Aru, Aysel Günay, Gülderen Yanıkkaya Demirel, Ayşe Gül Gürek, and Devrim Atilla

    Royal Society of Chemistry (RSC)
    3-Hydroxypyridin-2-thione bearing zinc and indium phthalocyanine derivatives, as photosensitizer agents have been synthesized and evaluated for their anti-cancer efficacy on two breast cancer cell lines, MDA-MB-231 and MCF-7 as well as a human endothelial cell line, HUVEC.

  • Zero-valent iron nanoparticles containing nanofiber scaffolds for nerve tissue engineering
    Umran Aydemir Sezer, Kevser Ozturk Yavuz, Gizem Ors, Sadık Bay, Basak Aru, Oguz Sogut, Tuba Akgul Caglar, Mehmet Recep Bozkurt, Esra Cagavi, Gülderen Yanikkaya Demirel,et al.

    Hindawi Limited
    Regeneration of nerve tissue is a challenging issue in regenerative medicine. Especially, the peripheral nerve defects related to the accidents are one of the leading health problems. For large degeneration of peripheral nerve, nerve grafts are used in order to obtain a connection. These grafts should be biodegradable to prevent second surgical intervention. In order to make more effective nerve tissue engineering materials, nanotechnological improvements were used. Especially, the addition of electrically conductive and biocompatible metallic particles and carbon structures has essential roles in the stimulation of nerves. However, the metabolizing of these structures remains to wonder because of their nondegradable nature. In this study, biodegradable and conductive nerve tissue engineering materials containing zero‐valent iron (Fe) nanoparticles were developed and investigated under in vitro conditions. By using electrospinning technique, fibrous mats composed of electrospun poly(ε‐caprolactone) (PCL) nanofibers and Fe nanoparticles were obtained. Both electrical conductivity and mechanical properties increased compared with control group that does not contain nanoparticles. Conductivity of PCL/Fe5 and PCL/Fe10 increased to 0.0041 and 0.0152 from 0.0013 Scm−1, respectively. Cytotoxicity results indicated toxicity for composite mat containing 20% Fe nanoparticles (PCL/Fe20). SH‐SY5Y cells were grown on PCL/Fe10 best, which contains 10% Fe nanoparticles. Beta III tubulin staining of dorsal root ganglion neurons seeded on mats revealed higher cell number on PCL/Fe10. This study demonstrated the impact of zero‐valent Fe nanoparticles on nerve regeneration. The results showed the efficacy of the conductive nanoparticles, and the amount in the composition has essential roles in the promotion of the neurites.

  • A Translational Study of a Silicon Phthalocyanine Substituted with a Histone Deacetylase Inhibitor for Photodynamic Therapy
    Başak Aru, Aysel Günay, Elif Şenkuytu, Gülderen Yanıkkaya Demirel, Ayşe Gül Gürek, and Devrim Atilla

    American Chemical Society (ACS)
    In this study, we synthesized and characterized a silicon phthalocyanine substituted with 3-hydroxypyridin-2-thione (SiPc-HDACi), designed to be a chemophotodynamic therapy agent acting as a histone deacetylase inhibitor, and we determined its photophysical, photochemical, and photobiological properties. Next, we evaluated its anticancer efficacy on MCF-7, double positive and MDA-MB-231, triple negative breast cancer cell lines, as well as on a healthy human endothelial cell line (HUVEC). Our results indicate that SiPc-HDACi can target nucleoli of cells, effectively inducing apoptosis while promoting cell cycle arrest thanks to its high singlet oxygen yield and its histone deacetylase downregulating properties, suggesting a powerful anticancer effect on breast cancer in vitro. Our further studies will be conducted with primary breast cancer cell culture to give a better insight into the anticancer mechanism of the compound.

  • Cytotoxicity, bactericidal and hemostatic evaluation of oxidized cellulose microparticles: Structure and oxidation degree approach
    Umran Aydemir Sezer, İsa Sahin, Basak Aru, Hulya Olmez, Gulderen Yanıkkaya Demirel, and Serdar Sezer

    Elsevier BV

  • Antiproliferative Activity of Chemically Characterized Propolis from Turkey and Its Mechanisms of Action
    Başak Aru, Etil Güzelmeric, Aslı Akgül, Gülderen Yanıkkaya Demirel, and Hasan Kırmızıbekmez

    Wiley
    AbstractThe aim of this study was to evaluate the ethanolic extract of propolis originated from northern Turkey for its antiproliferative, apoptotic and cell cycle arrest promoting effects on MCF7, HGC27, A549 cancer cell lines and a healthy cell line (HUVEC) in terms of DNA content, morphological features, expression of cell cycle checkpoint proteins p21, p53, Cyclin D1 and immune checkpoint protein PD‐L1. The extract showed moderate antiproliferative activity against all tested cancer cell lines with IC50 values in the range of 58.6–90.7 μg/mL in MTS assay. Further studies indicated that propolis extract exerted apoptotic effect on cancer cell lines, promoted cell cycle arrest through activation of p21 and resulted in accumulation at G0/G1 phase of cancer cells. Propolis treatment caused increased cell size, according to fluorescent imaging except for MCF7. HPTLC analysis revealed that 3‐O‐methylquercetin, chrysin, caffeic acid, CAPE, galangin and pinocembrin were the main components of the extract. The amounts of caffeic acid and CAPE in the extract were found to be 5.5 and 11.1 mg/g, respectively, by a validated HPLC method. Our study is the first one, revealing effect of propolis on PD‐L1 expression on certain cancer cell lines.

  • Polypropylene composite hernia mesh with anti-adhesion layer composed of polycaprolactone and oxidized regenerated cellulose
    Umran Aydemir Sezer, Vildan Sanko, Mehmet Gulmez, Basak Aru, Elif Sayman, Ali Aktekin, Fugen Vardar Aker, Gulderen Yanıkkaya Demirel, and Serdar Sezer

    Elsevier BV

  • PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans
    Tulay Guran, Gozde Yesil, Serap Turan, Zeynep Atay, Emine Bozkurtlar, AghaRza Aghayev, Sinem Gul, Ilker Tinay, Basak Aru, Sema Arslan,et al.

    Oxford University Press (OUP)
    Context Most of the knowledge on the factors involved in human sexual development stems from studies of rare cases with disorders of sex development. Here, we have described a novel 46, XY complete gonadal dysgenesis syndrome caused by homozygous variants in PPP2R3C gene. This gene encodes B″gamma regulatory subunit of the protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase involved in the phospho-regulation processes of most mammalian cell types. PPP2R3C gene is most abundantly expressed in testis in humans, while its function was hitherto unknown. Patients and methods Four girls from four unrelated families with 46, XY complete gonadal dysgenesis were studied using exome or Sanger sequencing of PPP2R3C gene. In total, four patients and their heterozygous parents were investigated for clinical, laboratory, immunohistochemical and molecular characteristics. Results We have identified three different homozygous PPP2R3C variants, c.308T&gt;C (p.L103P), c.578T&gt;C (p.L193S) and c.1049T&gt;C (p.F350S), in four girls with 46, XY complete gonadal dysgenesis. Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay. We have shown a decreased SOX9-Phospho protein expression in the dysgenetic gonads of the patients with homozygous PPP2R3C variants suggesting impaired SOX9 signaling in the pathogenesis of gonadal dysgenesis. Heterozygous males presented with abnormal sperm morphology and impaired fertility. Conclusion Our findings suggest that PPP2R3C protein is involved in the ontogeny of multiple organs, especially critical for testis development and spermatogenesis. PPPR3C provides insight into pathophysiology, as well as emerging as a potential therapeutic target for male infertility.

  • Process optimisation, biocompatibility and anti-cancer efficacy of curcumin loaded gelatine microparticles cross-linked with dialdeyhde carboxymethyl cellulose
    Zeynep Kocer, Basak Aru, Umran Aydemir Sezer, Gulderen Yanıkkaya Demirel, Ulker Beker, and Serdar Sezer

    Informa UK Limited
    Abstract In this study, we produced curcumin loaded gelatine microparticles, through spray-drying method, with dialdehyde carboxymethyl cellulose (DCMC) which is introduced as a new cross-linking agent for drug delivery systems and examined toxicities by comparison of traditional cross-linking agents. We employed various parameters in the production and tried to develop the most efficient drug delivery system through Taguchi method by examining efficiencies on gastric cancer under in vitro conditions. The results indicated gelatine microparticles cross-linked with DCMC offers more biocompatible drug delivery systems. The particle size of the microparticles produced via different parameters varies from 1.926 to 3.357 µm. Curcumin was substantially remained stable after 6 months. This study indicates potential use of DCMC cross-linked gelatine microparticles as drug delivery vehicle.