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AIM: Colon cancer is one of the main health problems worldwide. Cancer stem cells (CSCs) are referred to as tumor-initiating cells involved in tumor heterogeneity and dormancy. CSCs can cause drug resistance, metastasis, and recurrence of primary and metastatic cancers. The interactions and survival trends of colon cancer stem cells with other cells may be an alternative route for effective treatment. In our study, we aimed to evaluate the effects of asteoside on stem cell properties, apoptotic and inflammatory processes in primary (HCT-116) and metastatic (Colo-741) colon CSCs. METHERIALS AND METHODS: CSCs were obtained from both types of colon cancer cell lines with the MINIMACS system using the anti-CD133 reagent. Metastatic Colo-741 and non-metastatic HCT-116 CD133+ and CD133- cells were cultured with or without Acteoside for 48 hours. Expressions of Caspase-3, Bcl, Bax, and Fas-L for apoptosis, and IL-1β, TNF-α, IL-6, IL8 and IL-10 for inflammation were analyzed by indirect immunocytochemistry technique by performing H-Score. Changes in cell morphology were examined under an inverted microscope. RESULTS AND CONCLUSION: It was observed that Oct-4 expression decreased after acteocyte administration in both metastatic and non-metastatic colon cancer cells. In addition, Colo-741 increased the intensity of the Bax/Bcl ratio in both CD133+ and CD133- cells and increased caspase 3 expression. While acteoside did not immunohistochemically affect inflammation in metastatic COLO-741 cells, it contributed to the apoptotic process by changing the Bax/Bcl ratio. When the morphology of the cells was evaluated, it was observed that the number of apoptotic cells increased in COLO-741 CD133+ and CD133- cells.

Cellular senescence plays a key role in aging and age-related disease initiation. It is a highly dynamic and multistep process that can be stimulated by various stimuli, including cellular stress, DNA damage, telomere shortening, and oncogene activation. Also, senescence is a potent antitumor mechanism, by preventing the proliferation of cancerous cells. However, some of the senescent cells have apoptosis resistance and can cause recurrence in cancer. A new class of drugs termed senolytics selectively kill and eliminate senescent cells. In recent years, natural compounds such as quercetin have been discovered to be effective as senolytic agents. Quercetin is a phytochemical that has strong antioxidant properties and pro-apoptotic effects and has been investigated for many years. Additionally, it has great potential to be used as a senolytic agent. According to preclinical and early-phase clinical data of senolytic agent research, quercetin administration appears to be effective in preventing or alleviating cancer formation. In this paper, we review the importance of cellular senescence in carcinogenesis and the effects of quercetin on senescence, as well as quercetin's potential effects as a pro-apoptotic agent and suppressor of cancer cell proliferation.

Oosit matürasyonu prenatal dönemden puberteye kadar süren birçok proteinin karşılıklı etkileşimiyle kontrol edilen bir süreçtir. Matür oositin kalitesi ileri fertilizasyon ve implantasyon başarısını doğrudan etkileyerek kaliteli embriyo oluşumuna temel oluşturmaktadır. Oositin matürasyon süreci in vivo ve in vitro ortamlarda araştırma konularından biri olup günümüzde hem sürecin anlaşılması hem de kültür ortamındaki koşulların belirlenmesine yönelik çalışmalar devam etmektedir. N6-metiladenosin (m6A) en yaygın RNA modifikasyonlarından biridir. m6A metilasyonunda metil gruplarının eklenmesinden sorumlu metiltransferazlar (yazıcılar), metil gruplarının kaldırılmasından sorumlu dimetilazlar (siliciler) ve metil grubunu bağlayıcı proteinler (okuyucular) olmak üzere üç grup protein görev almaktadır. Son yıllarda kanser, metabolik hastalıklar gibi süreçlerde önemli rolleri olduğu kanıtlanan m6A metilasyonunun oogenez ve spermatogenez süreçlerindeki yeri ve önemi de yapılan çalışmalarla ortaya çıkarılmaktadır. Bu derlemede oosit matürasyonu ve m6A metilasyonunu tanımlanması, aralarındaki ilişkinin araştırılması ve sonuçta oosit matürasyonuna m6A metilasyonu ve/veya proteinlerinin direkt/indirekt etkilerinin tartışılması amaçlanmıştır.

Exosomes are nanoscale vesicles released from tumor-derived cells. They are very popular cancer biomarkers in non-invasive liquid biopsy diagnosis and evaluation of therapeutic response. Rapid analysis of exosomes with proteins or other biomarkers requires complex methods and has a relatively high cost. We indicate the fabrication of a biosensor for the detection of exosomes at low concentrations using immunological recognition strategies. The implementation of the biosensor consists of two steps: (i) functionalization of screen-printed electrodes (SPEs) with tetraspanin anti-CD63 antibodies and (ii) capturing exosomes by the electrode surface. Label-free detection of exosomes was successful with the Nyquist diagram, one of the main demonstrations of electrochemical impedance spectroscopy (EIS). In addition, we increased the consistency of the results by including the Bode diagrams of the measurements in our study. The proposed biosensor as a sensitive and reliable impedimetric method for detecting exosomes was established in a working range of 3.7 x 10( )3 to 3.7 x 10(8) particles mL(-1) with a detection limit of 2.0 x 10(3) particles mL(-1).

The purpose of this study was to investigate the effect of kisspeptin-54 on ovarian morphology and vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), protein kinase A (PKA) and protein kinase C (PKC) levels in an ovarian hyperstimulation syndrome (OHSS) rat model, which is a possible complication of controlled ovarian hyperstimulation. For this purpose, immature female Sprague–Dawley rats (25 days old, 30–40 g) were randomly divided into five groups (control, sham, OHSS model, short-term kisspeptin-54 administered OHSS model and long-term kisspeptin-54 administered OHSS model). Serum LH and FSH levels were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and quantitative RT-PCR were performed for VEGF, PEDF, PKA and PKC in ovaries and granulosa cells, respectively. It was observed that there was dilatation in fallopian tubes and an abnormal increase in ovarian weight and volume in the OHSS group, and these morphologies decreased with kisspeptin-54 treatment. After the administration of kisspeptin-54 in the OHSS group, VEGF, PKA and PKC levels reduced and PEDF levels increased in both mRNA and protein levels. It was determined that in the OHSS model, VEGF increased as PEDF decreased, and kisspeptin-54 reduced the effects of OHSS. It was determined that long-term kisspeptin-54 treatment was more effective than short-term administration. It is considered that kisspeptin-54 is an agent that protects ovarian reserve and oocyte maturation in women at risk of OHSS.

Giriş: Böbrek hücrelerinin elde edilmesinde kullanılan primer kültür yöntemi, böbrek hastalıklarının hücre düzeyinde değerlendirilmesi ve hücre fonksiyonlarının incelenmesi için olanak sağlamaktadır. Bu çalışmanın amacı böbrek primer kültürü için kullanılabilecek üç farklı izolasyon yönteminin hücre sağkalımı ve protol etkinliği açısından birbirleriyle karşılaştırılmasıdır. Gereç ve Yöntemler: Nefrektomi ile çıkarılan böbrek dokusu steril şartlarda mekanik, tripsin ve kollagenaz yöntemi ile ayrımlanarak podosit vasatı içerisinde kültüre edildi. Kültüre edilen hücrelerin podosin, vimentin, E-kaderin, TGF-β1, CD133, ZO-1 ve Nefrin dağılımlarının analizi immünositokimyasal yöntem ile yapıldı. Bulgular: Kollajenaz enzimatik yöntemi sonrasında hücrelerin kültürün 7. gününden itibaren, mekanik yöntemde ise 13. günden itibaren epiteloid karakter aldıkları gözlenirken, tripsin enzimatik yönteminde 13. günde kültürde artan fuziform yapıdaki hücreler gözlendi. Her üç yöntem ile böbrek dokusundan elde edilen podosit hücrelerin immunositokimyasal analizi sonrasında, elde edilen hücrelerde vimentin, E-kaderin, TGF-β, CD133, ZO-1 immunoreaktiviteleri farklılık gösterir iken, podosin ve nefrin immunoreaktivitelerinin kollajenaz enzimatik yöntemi ile elde edilen hücrelerde kuvvetli olduğu saptandı. Tartışma: Bu çalışmada, farklı proteinlerin immunositokimyasal boyamaları ile kontrol edilen böbrek hücreleri için üç farklı primer kültür teknikleri karşılaştırıldığında, kollajenaz ile muamele edilen böbrek dokusundan daha yüksek verimle hücre saflaştırılabildiği gözlendi. Podosit hücrelerinin kültüre edilmesinde hücre sağkalım verimi ve protokol etkinliği açısından kollajenaz yönteminin en uygun yöntem olduğu gösterildi.

Aim Polycystic Ovarian Syndrome (PCOS) is a complex endocrine disease and is the most common cause of infertility in women due to ovulation disorder. Although the distinctive morphological features of the polycystic ovary were clearly evaluated, the specific oocyte maturation molecules that are affect oocyte maturation and oocyte quality are currently not understood. In addition, the effect of drugs used to induce ovulation in PCOS on oocyte maturation is unknown. In this study it is aimed to investigate the changes of oocyte maturation proteins (Nobox, Foxl2, Cep55, Cx37, Cx43) post ovulation induction treatment. Materials and Methods Four-week-old, female Balb/c mice were subcutaneously injected 6mg/100g dehydroepiandrosterone (DHEA) for 21 consecutive days for experimental PCOS models and divided four groups. In control group, no injections performed. PCOS group, after DHEA administration was not applied any treatment. Treatment groups were given clomiphene citrate (1,5 mg/kg) alone or clomiphene citrate (1,5 mg/kg), metformin (12 mg/kg) and pioglitazone (0,20 mg/kg) as a combine for consecutive 5 days. The distributions of molecules were evaluated by indirect immunoperoxidase staining method in ovarian tissues and immunofluorescence staining method for oocytes. Intensity of immunofluorescence evaluated by ImageJ. Results The formation of the PCOS model was demonstrated by the glucose tolerance test, histological and morphological evidence. It was determined that the expression of all investigated molecules significantly decreased in the ovarian tissues of PCOS group but increased in the treated groups. In oocytes, intensities of Nobox, Foxl2, Cep55 and Cx43 were significantly increased in clomiphene citrate administered group compared to the PCOS group. Conclusion This study is the first to investigate the effect of drugs used for providing ovulation induction and reducing insulin resistance as single or combined treatments in PCOS mice model through maturation molecules. Both in vivo and in vitro oocyte maturation may trigger with target-specific treatment in PCOS patients. In addition, new molecules could be used in control of the in vitro oocyte maturation during treatment.

Diabetes mellitus is a significant health problem that is caused by chronic hyperglycaemia as a result of inadequate insulin production or ineffective insulin action in the body. In recent years, many new pharmacological and non-pharmacological therapies have been developed for improving pancreatic insulin secretion and insulin resistance. Resveratrol is a natural and biologically active stilbenoid polyphenol present in various plant species and has the potential to benefit diabetes. The anti-diabetic actions of resveratrol have also been extensively studied in diabetic human and animal models. Moreover, resveratrol might affect insulin sensitivity by regulating visceral fat derivated adipokine levels. The use of resveratrol in combination with anti-diabetic therapies or alone may have significant potential for the management of diabetes mellitus. This review provides an overview of the anti-diabetic action of resveratrol as well as the possible mechanisms that have an effect on insulin secretion and insulin resistance in diabetics.

Objective: Quercetin is a phytochemical that is regarded as a potential anticancer agent in colon cancer prevention. Exosomes are nanovesicles secreted by normal or cancer cells, which transport miRNAs and proteins and participate in intercellular communication as a cargo. Cytotoxicity, exosomal miRNA secretion, and distribution of Dicer, Ago2, CD9, CD63 and eIF2α in quercetin applied Colo 320 and Colo 741 colon cancer cell lines were aimed.Materials and Methods: The cytotoxicity test that we used to evaluate cell viability is MTT assay. The distribution of Dicer, Ago2, CD9, CD63 and eIF2α in both cell lines were analyzed using the indirect immunoperoxidase technique. The exosomal miRNA levels were evaluated by using a miRCURY™ Kit.Results: Decreased eIf2α immunoreactivity following quercetin application was significant in Colo 741 colon cancer cells. Increased Dicer and CD9 immunoreactivities were significant between Colo 320 and Colo 741 colon cancer cells. Additionally, after quercetin application, exosomal miRNA concentrations were increased in both Colo 320 and Colo 741 cell lines.Conclusion: According to our results, total exosomal miRNA concentration and levels of associated proteins were affected after quercetin administration. Additionally, the change in the immunoreactivity of the related proteins after quercetin application differed according to the cell type and origin.

The detection and control of pro-inflammatory response is crucial in the early stages of viral infection. Coronavirus disease 2019 (COVID-19) is an emerging viral disease of global concern and optimal treatment has yet to be determined. Unknown response of treatment of COVID-19 is important during patient monitoring. IL-6 is one of the key cytokines after activated macrophages. Therefore, control of systemic IL-6 levels in SARS-CoV-2 infected patients may be a parameter for COVID-19 disease. This review is focused on the induction of IL-6 after viral infections as a target molecule for monitoring cellular response.

Boswellia sacra Flueck essential oil is obtained from frankincense obtained from Boswellia sacra trees. The aim of this study was to investigate the in vitro anti-cancer activity of Boswellia sacra...

Objectives Mesenchymal stem cells are self-renewing stem cells. The human foreskin has potential to be used as a source of stem cells. The aim of the study was to obtain spheroid formation of human foreskin cells (hnFSSCs) isolated from newborn human foreskin tissue. In addition, the apoptotic and proliferative effects of a traditional plant, Corchorus olitorius L. (C. olitorius), on hnFSSC spheroids were investigated. Materials and methods After a routine circumcision procedure the cells were isolated and cultured in suitable medium. The plant leaves was extracted with ethanol and their composition was analyzed by liquid chromatography coupled with mass spectrometry (LC-MS/MS). The foreskin stem cells were characterized immunocytochemically by CD45, CD34, and CD90 antibodies. hnFSSC spheroids were formed using the hanging drop technique. Immunofluorescence staining was used on the obtained spheroids to determine the distribution of caspase-3 and Ki-67 after being treated with C. olitorius extract for 48 h. Results Immunostaining analysis showed that hnFSSCs were positive for CD45 and CD34 and negative for CD90. According to LC-MS/MS C. olitorius was rich in flavanols and hydrocinnamic acid derivatives. Although the spheroids obtained were loose and floating, the cells interacted with each other. Caspase-3 activity was higher in the control group than in the extract-treated group and Ki-67 was higher in the extract-treated group than in the control group, suggesting that the plant might have the capacity to increase stem cell proliferation due to its rich polyphenolic content. Conclusion The results suggest that hnFSSCs and spheroids might be used in stem cell generation, tissue repair and renewal as human foreskin tissue has potential to be used as a stem cell source. C. olitorius also increased proliferation of hnFSSCs, showing that polyphenols might increase proliferation of stem cells.

The aim of the study was to establish anSK-N-AS human neuroblastoma cells were used. To develop anAfter 24 hours of 6-hydroxydopamine administration at 50 μM, higher αlfa-synuclein and lower dopamine levels were found in PD model than SK-N-AS cells. Cell viability was similar between SK-N-AS andCatechin and EGCG increased cell viability in PD model neuron cells. Both components showed anti-apoptotic and anti-inflammatory effects. Catechin may be more effective in preventing damage to neurons PD.

The prevalence, incidence and mortality rates of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are gradually increasing. New approaches are being developed to manage the progression and treatment of neurodegenerative diseases. Catechins, polyphenolic compounds, are key compounds that demonstrate therapeutic effects with their properties such as antioxidant, anti-inflammatory, anti-apoptotic properties in the prevention and treatment of neurodegenerative diseases. The therapeutic effects of catechins have been exhaustively studied in human and animal models. Catechins can have anti-inflammatory effects by suppressing inflammatory pathways and cytokines, as well as antioxidant effects such as chelating metal ions and scavenging radicals. They might reduce phosphorylation of tau proteins, aggregation of amyloid-beta and apoptotic proteins release. They can also decrease alpha-synuclein accumulation and increase dopamine levels. With all these effects, they can have an effect on neurodegenerative diseases. This review points to the potential mechanisms of catechins in neurodegenerative diseases, based on their findings in the literature review. Key teaching pointsCatechins can reduce amyloid-β plaque aggregation and tau phosphorylation.Catechins can decrease alfa-synuclein levels.Catechins can protect neuronal cells with their anti-apoptotic effect.More comprehensive studies are needed to clarify this issue.

AIM The dorsal nerve of the penis (DNP) is the terminal branch of the pudendal nerve which is responsible for the somatic innervation of the penis. This study aims to outline any direct role of the DNP in the hemodynamics of erection histologically and physiologically. MATERIALS AND METHODS Fifteen Wistar albino rats were sorted into the electrical activity (n = 6), intracavernous pressure (n = 4), and control (n = 5) groups. The dorsal nerve was electrostimulated and the simultaneous changes in intracavernous pressure and smooth muscle activity were recorded. Penile tissues were collected, fixed, and sectioned, the slides were stained with either hematoxylin-eosin for morphological evaluation or using the indirect immunoperoxidase technique to analyze the distributions of eNOS, iNOS, and nNOS. RESULTS During electrostimulation, there was a simultaneous statistically significant decrease in the electrical activity inside the corpora in electromyography and an increase in intracavernous pressure. eNOS and iNOS immunoreactivities were higher in the study group than in the control group. nNOS immunoreactivity was moderate in both study and control groups. CONCLUSION Some fibers in the dorsal nerve of penis continue into the corpora cavernosa through the tunica albuginea and have an active, direct role in the hemodynamic process of erection, which may be complementary to the main route of innervation.

Background HAMLET (human α-lactalbumin made lethal to tumor cells) and sulindac are active ingredients which are used in the treatment of cancers. Under both in vivo and in vitro conditions, HAMLET binds to the surface of tumor cells and enters the cells. Sulindac is one of nonsteroidal anti-inflammatory drugs. It inhibits the growth of tumor cells by inducing the apoptosis. In our study, we aimed to investigate effects of α-lactalbumin and sulindac on COLO-320 primary and COLO-741 metastatic human colon carcinoma cell lines via mitochondrial apoptotic pathway by indirect immunocytochemistry and TUNEL assays. Materials and methods The effects of α-lactalbumin and sulindac were assessed by using MTT assay at 24, 48 and 72 h and apoptosis markers caspase-3, caspase-9 and cytochrome-c were detected using immunocytochemistry and TUNEL methods. Results It was appeared that α-lactalbumin and sulindac may triggger mechanisms of apoptosis in both primary and metastatic colon carcinoma cell lines and the primary colon carcinoma cell line was affected more than the metastatic cells. Conclusion It is proposed that α-lactalbumin and sulindac can be used in cancer treatments and future in vivo experiments.

This study aimed to evaluate cytotoxic effects and the apoptosis of Gallium-Aluminum-Arsenide (GaAlAs) diode laser irradiation, sodium hypochlorite (NaOCl), ozonated water and ethylene diamine tetraacetic acid (EDTA) on stem cells from human exfoliated deciduous teeth (SHEDs). Cells were exposed to EDTA (5%, 8.5%, 17%), NaOCl (1%, 2.5%, 5%) ozonated water (5, 10, 20 μg/ml) and GaAlAs diode laser irradiation (energy densities of 0.5, 1, 1.5 j/cm2). Culture medium included D-MEM, supplemented with 15% foetal bovine serum, 1% l -glutamine, 1% penicillin-streptomycin, 1% gentamycin, amphotericin-B and served as control group. The prepared irrigants were added to the relevant wells and incubated with the cells at 37 °C for 5, 10 and 15 min. The cells in the laser group were also incubated at 37 °C for 5, 10 and 15 min after the laser application. Cell viability and proliferation were analysed with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The percentage of cell viability showed a significant reduction in all concentrations of the EDTA and NaOCl groups when compared to the control group, diode laser irradiation and ozonated water groups at 5th, 10th and 15th minutes respectively but high cytotoxic effects of all EDTA and NaOCl groups with decreased over 50% of cell viability were observed at the 15th minute. Also EDTA group with 17% concentration (17%E) presented the lowest survival rate on SHEDs with mean of 21.67% ± 6.101 at this time interval. The lowest toxic effects were observed at the 5th minutes compared to other time periods at experimental groups. For detection of apoptotic cells, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method was performed. According to the MTT results, doses showed the highest toxicity (cell survival decreased over 50%) in each group were selected for TUNEL assay (17% EDTA; 1% NaOCl; 10 μg/ml Ozonated water; 1.5 j/cm2 diode laser irradiation). The significantly lowest percentages of TUNEL-positive cells were detected in ozonated water (10.67% ± 2.93) and diode laser irradiation (13.24% ± 7.61) compared to EDTA (39.89% ± 11.54) and NaOCl (31.15% ± 10.64) respectively. Also the difference between percentage of TUNEL-positive cells in EDTA and NaOCl groups was not significant. Synergistic combination of ozonated water and diode laser irradiation may be used in the disinfection step of necrotic root canals.

Objective: Exosomes are cargo systems that carry proteins, mRNAs and miRNAs and cause functional changes in the cells/tissues they target. CD63 is the key protein for the identification and isolation of exosomes. It is known that pharmacological agents used in controlled ovarian hyperstimulation (COH) protocols induce ovulation by increasing the number and quality of oocytes, but their effects on endometrial cells are not fully understood. In this study, it was aimed to evaluate the effects of drugs used in COH protocols on CRL-1671 human endometrium cells on exosome marker CD63.Materials and Methods: CRL-1671 cells were cultured for 8 days as control group, growth hormone (GH) treated group, Gonadotropin (GnTR) treated group, GH+GnTR treated group, Letrozole (L)+GnTR treated group and triple combined (L+GnTR+GH) group. At the end of the incubation, the distribution of CD63 in the cells was examined using the indirect-immunocytochemistry technique. Results: It was observed that CD63 immunoreactivity was moderate (++) in the control group, strong (+++) in the GnTR and L+GnTR groups, and moderate (++) in the other treated groups. The H-score values were calculated as 298 ± 6.71; 300 ± 5; 397 ± 12.55; 303 ± 2.74; 302 ± 5.70 and 391 ± 4.18, respectively. A significant difference was found between the GnTR and L+GnTR groups compared to the control group (p, Giriş ve Amaç: Eksozomlar; protein, mRNA ve miRNA’ları taşıyan ve hedefledikleri hücrelerde/dokularda fonksiyonel değişikliklere neden olan kargo sistemleridir. CD63, eksozomların tanımlanması ve izolasyonu için anahtar proteindir. Kontrollü ovaryan hiperstimülasyonu (KOH) protokollerinde kullanılan farmakolojik ajanların oosit sayısını ve kalitesini arttırarak ovulasyonu indüklediği bilinmekte fakat endometriyum hücreleri üzerindeki etkileri tam olarak bilinmemektedir. Bu çalışmada; CRL-1671 insan endometriyum hücrelerinde, KOH protokollerinde kullanılan ilaçlarının eksozom belirteci olan CD63 üzerine etkilerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: CRL-1671 hücreleri; kontrol grubu, büyüme hormonu (GH) uygulanan grup, Gonadotropin (GnTR) uygulanan grup, GH+GnTR uygulanan grup, Letrozol (L)+GnTR uygulanan grup ve üçlü kombine (L+GnTR+GH) grubu olacak şekilde 8 gün boyunca kültüre edildi. İnkübasyon sonunda hücrelerde CD63 dağılımı indirekt-immunositokimya tekniği ile incelendi.Bulgular: CD63 immunoreaktivitesinin kontrol grubunda orta (++), GnTR ve L+GnTR gruplarında kuvvetli (+++) ve diğer ilaç uygulanan gruplarda orta (++) şiddette olduğu gözlendi. H-score değerleri sırası ile 298 ± 6,71; 300 ± 5; 397 ± 12,55; 303 ± 2,74; 302 ± 5,70 ve 391 ± 4,18 olarak hesaplandı. Kontrol grubu ile karşılaştırıldığında GnTR ve L+GnTR uygulanan gruplarda istatistiksel anlamlı farklılık belirlendi (p

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells. The effects of the aging on these abilities of MSCs have not been adequately clarified. in this study, alterations in immunomodulatory abilities of MSCs caused by aging were investigated. For this, dental pulp (DP) MSCs and peripheral blood mononuclear cells (PBMCs) of elderly and young donors were co-cultured age-matched and cross. We detected that the effects of DP-MSCs on Th1 and Th2 cells and their specific cytokines IFN-gamma and IL-4 are not affected by aging. However, we observed that young and elderly DP-MSCs have different effects on Th17 and Treg cells. Th17 frequencies of young and elderly PBMCs were significantly increased only by young DP-MSCs, in contrast, Treg frequencies were significantly increased by elderly DP-MSCs. IL-6, IL-17a and HGF levels of both young and elderly PBMCs showed a significant increase only by young DP-MSCs, but TGF-beta levels were significantly increased only by elderly DP-MSCs. The oral cavity is home to a rich microflora. The interactions of dental tissues with this microflora can lead them to acquire different epigenetic modifications. Aging can affect the microflora composition of the oral cavity and change this process in different directions. According to our findings, DP-MSCs are effective cells in the regulation of CD4(+) T cells, and their effects on Th1 and Th2 cells were not affected by aging. However, pleiotropic molecules IL-6 and HGF expressions, which are important in dental and bone tissue regeneration, decreased significantly in elderly DP-MSCs. This situation may have indirectly made a difference in the modulation effects of young and elderly DP-MSCs on the Th17 and Treg cells., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213S078], We thank to Dr. Zehra Seda Unal, and M.Sc. Ceren Ozel from Kocaeli University, Stem Cell and Gene Therapies Research and Application Center, for assistance and comments on ELISA and flow cytometry analyses. The Scientific and Technological Research Council of Turkey (TUBITAK) supported this study, whose reference number is 213S078.

Mathematical modeling is a key tool in understanding complicated behavior of large signal transduction networks. In this paper a mathematical model is developed to understand the complex signaling behavior of induced apoptosis in Colo-320 and Colo-741 cell lines. The model studies the intrinsic pathway of apoptosis induced by Apaf-1, Cyt-c, and Caspase 3. Experimentally these tests were carried out five times for three groups; namely Control, DCM and Aqueous groups. The main aim is to compare the rate of the occurrence of apoptosis in the two cells Colo-320 and Colo-741 using experimental data. Numerical results reveal that apoptosis takes place at the same time in DCM for Colo-320 and Colo-741, but slightly faster in Aqueous group for Colo-320. It was observed that it took place between the 5–7th h in all the cases.

Objective: Ovarian cryopreservation is a useful alternative for fertility preservation in assisted reproductivetechnologies. In spite of many advances in the vitrification procedure, this technique is still considered experimental.Therefore in this study, we aimed to investigate the expressions of mitochondrial fusion (MFN1, MFN2 and OPA1),fission (DRP1), mitophagy (PARKIN, PINK1) and transport (MIRO-1, MILTON) proteins in ovarian tissues by qPCRtechnique after vitrification.Materials and Methods: To investigate the mitochondrial dynamics after vitrification, the ovaries were recoveredfrom 6-8 week old healthy female mice (No: 12) and were divided into vitrification and control groups. Vitrificationcarried out using ethylene glycol, dimethylsulfoxide and sucrose. After total RNA isolation from ovaries in controland vitrification groups, qPCR technique was performed to determine the expression rate of target genes. The relativegene expressions of the target genes were evaluated according to 2−∆∆Ct method.Results: Histological evaluation revealed that ovaries in the control group were shown normal morphology while thetissue integrity of the ovaries in the vitrification group is disrupted, some follicles are degenerated and granulosa cellswere shed into antrum. According to our qPCR results, outer membran fusion proteins MFN1 gene expressiondecreased 1,12 fold and inner membran protein OPA-1 increased 1,36 fold in the vitrification group compared thecontrol group. The mitochondrial fission protein DRP-1 gene expression increased 1,20 fold in the vitrification group.The mitophagy proteins PINK-1 and PARKIN genes expressions decreased 1,34 and 3,75 fold respectively in thevitrification group. The transport proteins; MIRO-1 gene expression decreased 1,16 fold but MILTON (TRAK-1) geneexpression sharply increased 2,28 fold compared the control group.Conclusion: The alternation of the mitochondrial dynamics related gene expressions may lead a decrease in themitochondrial function during the ovarian vitrification and may reduce the potential of oocyte maturation and embryodevelopment, Giriş ve Amaç: Ovaryan kriyoprezervasyonu, yardımcı üreme teknolojilerinde doğurganlığın korunması için yararlıbir alternatiftir. Vitrifikasyon prosedüründeki birçok ilerlemelere rağmen bu teknik hala deneysel olarak kabuledilmektedir. Bu nedenle bu çalışmada, vitrifikasyon sonrası over dokularında mitokondriyal füzyon (MFN1, MFN2ve OPA1), fisyon (DRP1), mitofaji (PARKIN, PINK1) ve transport (MIRO-1, MILTON) proteinlerinin ifadeleriniqPCR tekniği ile araştırmayı amaçladık.Gereç ve Yöntemler: Vitrifikasyon sonrası mitokondriyal dinamikleri araştırmak için, overler 6-8 haftalık sağlıklıdişi farelerden (No: 12) alındı ve vitrifikasyon ve kontrol gruplarına ayrıldı. Vitrifikasyon, etilen glikol,dimetilsülfoksit ve sukroz kullanılarak gerçekleştirildi. Kontrol ve vitrifikasyon gruplarındaki overlerden total RNAizolasyonu yapıldıktan sonra hedef genlerin ifade oranlarını belirlemek için qPCR tekniği kullanıldı. Hedef genlerinrelatif gen ifadeleri 2−∆∆Ct yöntemine göre değerlendirildi.Bulgular: Histolojik değerlendirme kontrol grubundaki overlerin normal morfoloji gösterdiği, vitrifikasyongrubundaki overlerin ise doku bütünlüğünün bozulduğunu; bazı foliküllerin dejenere olduğunu ve granülozahücrelerinin antruma döküldüğünü ortaya koydu. qPCR sonuçlarımıza göre vitrifikasyon grubunda kontrol grubunakıyasla dış membran füzyon proteini MFN1 gen ifadesinin 1,12 kat azaldığı ve iç membran proteini olan OPA-1’inifadesinin 1,36 kat arttığı saptandı. Mitokondriyal fisyon proteini DRP-1 gen ifadesinin vitrifikasyon grubunda 1,20kat arttığı bulundu. Mitofaji proteinleri olan PINK-1 ve PARKIN gen ifadelerinin vitrifikasyon grubunda sırasıyla 1,34ve 3,75 kat azaldığı tespit edildi. Kontrol grubuna göre karşılaştırıldığında transport proteinlerinin; MIRO-1 genifadesinin 1,16 kat azaldığı ancak MILTON (TRAK-1) gen ifadesinin 2,28 kat arttığı saptandı.Sonuç: Mitokondriyal dinamikler ile ilişkili gen ifadelerindeki değişimler, ovaryan vitrifikasyonu sırasındamitokondriyal fonksiyonda bir azalmaya yol açabilir ve oosit maturasyonu ve embriyo gelişimi potansiyeliniazaltabilir

Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells. The effects of the aging on these abilities of MSCs have not been adequately clarified. In this study, alterations in immunomodulatory abilities of MSCs caused by aging were investigated. For this, dental pulp (DP) MSCs and peripheral blood mononuclear cells (PBMCs) of elderly and young donors were co-cultured age-matched and cross. We detected that the effects of DP-MSCs on Th1 and Th2 cells and their specific cytokines IFN-γ and IL-4 are not affected by aging. However, we observed that young and elderly DP-MSCs have different effects on Th17 and Treg cells. Th17 frequencies of young and elderly PBMCs were significantly increased only by young DP-MSCs, in contrast, Treg frequencies were significantly increased by elderly DP-MSCs. IL-6, IL-17a and HGF levels of both young and elderly PBMCs showed a significant increase only by young DP-MSCs, but TGF-β levels were significantly increased only by elderly DP-MSCs. The oral cavity is home to a rich microflora. The interactions of dental tissues with this microflora can lead them to acquire different epigenetic modifications. Aging can affect the microflora composition of the oral cavity and change this process in different directions. According to our findings, DP-MSCs are effective cells in the regulation of CD4