Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells.

Numerous chromatin regulators are required for embryonic stem (ES) cell self-renewal and pluripotency, but few have been studied in detail. Here, we examine the roles of several chromatin regulators whose loss affects the pluripotent state of ES cells. We find that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy. Furthermore, both Mbd3 and Brg1 play key roles in the biology of 5-hydroxymethylcytosine (5hmC): Mbd3 colocalizes with Tet1 and 5hmC in vivo, Mbd3 knockdown preferentially affects expression of 5hmC-marked genes, Mbd3 localization is Tet1-dependent, and Mbd3 preferentially binds to 5hmC relative to 5-methylcytosine in vitro. Finally, both Mbd3 and Brg1 are themselves required for normal levels of 5hmC in vivo. Together, our results identify an effector for 5hmC, and reveal that control of gene expression by antagonistic chromatin regulators is a surprisingly common regulatory strategy in ES cells.

Secondary findings in 622 Turkish clinical exome sequencing data.

CES (Clinical Exome Sequencing) is a method that we use to diagnose rare diseases with nonspesific clinical features. Besides primary indication for testing genetic information may be detected about diseases which have not yet emerged. ACMG guidelines recommend to report pathogenic variations in medically actionable 59 genes. In this study we evaluated CES data of 622 cases which were tested for various indications. According to ACMG recommendations 59 genes were screened for reportable variations. The detected variations were reviewed using distinct databases and ACMG variation classification guidelines. Among 622 cases 13 (2.1%) had reportable variations including oncogenetic, cardiogenetic disorders, and malignant hyperthermia susceptibility-related genes. In 15 cases (2.4%) heterozygous pathogenic and likely pathogenic variations were detected in genes showing autosomal recessive inheritance. Ten novel variations causing truncated protein or splicing defect were reported. We detected 11 variations having conflicting interpretations in databases and 30 novel variations, predicted as likely pathogenic via insilico analysis tools which further evaluations are needed. As to our knowledge this is the first study investigating secondary findings in Turkish population. To extract the information that may lead to prevent severe morbidities and mortalities from big data is a valuable and lifesaving effort. Results of this study will contrbute to existing knowledge about secondary findings in exome sequencing and will be a pioneer for studies in Turkish population.

Antimicrobial screening of some selected Turkish medicinal plants.

For many years, plants are used for treatment of various diseases. In general, plants have rather more therapeutic benefits and fewer adverse effects compared with the synthetic drugs. The purpose of this study was to determine the in vitro antimicrobial potentials of fifteen plant species from Anatolia region of Turkey against some selected bacteria and a yeast strain. The extracts from belong to nine families were examined against Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 43300 (MRSA), Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Candida albicans ATCC 10231 using disc diffusion and micro dilution methods. According to the obtained results, all plant extracts showed different ranges of antibacterial activity against S. aureus ATCC 43300 and S. aureus ATCC 25923 strains. Flower and leaves extracts of R. lutea, leaves extract of E. ritro, flower and leaves extracts of H. europaeum, leaves extract of E. macroclada, fruit and leaves extracts of Z. fabago, flower extract of C.crupinastrum, leaves extract of D. tenuifolia showed different ranges of antifungal activity against C. albicans.

Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.

ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses.

Expression of prostaglandin E2 receptor subtypes in human pterygium and normal conjunctiva: immunohistochemical study.

PURPOSE: In the present study, we aimed to evaluate the expression of EP receptors in primary and recurrent human pterygium tissues. METHODS: Pterygium samples were collected from 65 patients with primary pterygium and 16 patients with recurrent pterygium. Normal conjunctival tissues were collected from nasal interpalpebral area from 17 patients without systemic and any other ocular pathology. Expression of EP receptors was evaluated by immunohistochemistry. The median value for each receptor staining score (RSS) was determined in normal conjunctival specimens. In this study, RSS of > median value was defined as positive staining or high expression and ≤ median value as negative staining or weak expression in specimens. Chi-square test was used for statistical analysis, and p value of less than 0.05 was considered significant. RESULTS: Stromal expression of EP1 was significantly higher in primary and recurrent pterygium specimens compared to normal conjunctival tissues (p = 0.007 and p = 0.002, respectively). Epithelial expressions of EP2 and EP3 were significantly lower in primary pterygium specimens compared to normal conjunctival tissues (p = 0.005 and p < 0.0001, respectively), and stromal expressions were insignificant. Stromal expression of EP4 was significantly higher in primary and recurrent pterygium specimens compared to normal conjunctival tissues (p = 0.002 and p = 0.012, respectively). CONCLUSIONS: Expression of EP receptors has been up- or downregulated in primary and recurrent pterygium tissues, and these receptors may play a role in formation and recurrence of pterygium.

A system for genome-wide histone variant dynamics in ES cells reveals dynamic MacroH2A2 replacement at promoters.

Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states, chromatin insulator function, chromosome folding, and the maintenance of the pluripotent state of embryonic stem cells. Here, we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues, recapitulating expected characteristics of the well characterized H3.3 histone variant. We extended this system to the less-studied MacroH2A2 variant, commonly described as a "repressive" histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated cells. Unexpectedly, we found that while large intergenic blocks of MacroH2A2 were stably associated with the genome, promoter-associated peaks of MacroH2A2 exhibited relatively rapid exchange dynamics in ES cells, particularly at highly-transcribed genes. Upon differentiation to embryonic fibroblasts, MacroH2A2 was gained primarily in additional long, stably associated blocks across gene-poor regions, while overall turnover at promoters was greatly dampened. Our results reveal unanticipated dynamic behavior of the MacroH2A2 variant in pluripotent cells, and provide a resource for future studies of tissue-specific histone dynamics in vivo.

Evaluation of radiation safety in (177)Lu-PSMA therapy and development of outpatient treatment protocol.

The aim of this study is to investigate the outpatient treatment protocol and radiation safety of a new-emerging lutetium-177 ((177)Lu) prostate specific membrane antigen (PSMA) therapy. This work analyzed the dose rate of 23 patients treated with 7400 MBq (177)Lu-PSMA at different distances (0, 0.25, 0.50, 1.0 and 2.0 m) and variable time marks (0, 1, 2, 4, 18, 24, 48 and 120 h) after the termination of infusion. Blood samples were withdrawn from 17 patients within the same group at 3, 10, 20, 40, 60 and 90 min and 2, 3, 24 h after termination of infusion. Seven different patients were asked to collect urine for 24 h and a gamma well counter was used for counting samples. Family members were invited to wear an optically stimulated luminescence dosimeter whenever they were in the proximity of the patients up to 4-5 d. The total dose of the medical team including the radiopharmacist, physicist, physician, nurse, and nuclear medicine technologist was estimated by an electronic personnel dosimeter. The finger dose was determined using a ring thermoluminescent dosimeter for the radiopharmacist and nurse. The mean dose rate at 1 m after 4 h and 6 h was 23 ± 6 µSv h(-1) and 15 ± 4 µSv h(-1) respectively. The mean total dose to 23 caregivers was 202.3 ± 42.7 µSv (range: 120-265 µSv). The radiation dose of the nurse and radiopharmacist was 6 and 4 µSv per patient, respectively, whereas the dose of the physicist and physician was 2 µSv. The effective half life of blood distribution and early elimination was 0.4 ± 0.1 h and 5 ± 1 h, respectively. Seven patients excreted a mean of 45% (range: 32%-65%) from the initial activity in 6 h. Our findings demonstrate that (177)Lu-PSMA is a safe treatment modality to be applied as an outpatient protocol, since the dose rate decreases below the determined threshold of <30 µSv h(-1) after approximately 5 h and degrades to 20 µSv h(-1) after 6 h.

The potential medicinal value of plants from Asteraceae family with antioxidant defense enzymes as biological targets.

CONTEXT: Plants and most of the plant-derived compounds have long been known for their potential pharmaceutical effects. They are well known to play an important role in the treatment of several diseases from diabetes to various types of cancers. Today most of the clinically effective pharmaceuticals are developed from plant-derived ancestors in the history of medicine. OBJECTIVE: The aim of this study was to evaluate the free radical scavenging activity and total phenolic and flavonoid contents of methanol, ethanol, and acetone extracts from flowers and leaves of Onopordum acanthium L., Carduus acanthoides L., Cirsium arvense (L.) Scop., and Centaurea solstitialis L., all from the Asteraceae family, for investigating their potential medicinal values of biological targets that are participating in the antioxidant defense system such as catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). MATERIALS AND METHODS: In this study, free radical scavenging activity and total phenolic and flavonoid contents of the plant samples were assayed by DPPH, Folin-Ciocalteu, and aluminum chloride colorimetric methods. Also, the effects of extracts on CAT, GST, and GPx enzyme activities were investigated. RESULTS AND DISCUSSION: The highest phenolic and flavonoid contents were detected in the acetone extract of C. acanthoides flowers, with 90.305 mg GAE/L and 185.43 mg Q/L values, respectively. The highest DPPH radical scavenging was observed with the methanol leaf extracts of C. arvense with an IC50 value of 366 ng/mL. The maximum GPx and GST enzyme inhibition activities were observed with acetone extracts from the flower of C. solstitialis with IC50 values of 79 and 232 ng/mL, respectively.

Evaluation of circulating miRNAs in wet age-related macular degeneration.

PURPOSE: In the present study, we aimed to investigate the changes in plasma miRNA in patients with wet age-related macular degeneration. METHODS: The expression profiles of 384 miRNAs in plasma from 33 patients (22 male, 11 female) who were diagnosed with wet age-related macular degeneration with fundus examination, fundus fluorescein angiography, and optical coherence tomography and 31 controls (17 male, 14 female) were evaluated using high-throughput quantitative real-time PCR. RESULTS: Our results demonstrated that the expression level of five miRNAs (miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p) was significantly upregulated in patients with age-related macular degeneration when compared to the control group (p<0.05). The expression level of 11 miRNAs (miR-21-5p, miR-25-3p, miR-140-3p, miR-146b-5p, miR-192-5p, miR-335-5p, miR-342-3p, miR-374a-5p, miR-410, miR-574-3p, and miR-660-5p) was significantly downregulated in patients (p<0.05). In addition, ten miRNAs (miR-26b-5p, miR-27b-3p, miR-29a-3p, miR-139-3p, miR-212-3p, miR-324-3p, miR-324-5p, miR-532-3p, miR-744-5p, and miR-Let-7c) were expressed only in the patient group. CONCLUSIONS: Our results suggest that plasma miRNA levels may change in wet age-related macular degeneration. These molecules may have an important therapeutic target in patients who are unresponsive to antivascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as age-related macular degeneration.

Central retinal artery occlusion and irreversible blindness due to paranasal sinus infection in a pregnant woman.

Paranasal sinus infections can cause severe orbital complications leading to blindness. The mechanism for blindness with paranasal sinus infection can involve thrombophlebitis ischemia by valveless orbital veins, pressure ischemia resulting in central artery occlusion, or optic neuritis as a reaction to adherent infection. We present a case of orbital cellulitis leading to central retinal artery occlusion and blindness in a 30-week pregnant woman.

Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study.

PURPOSE: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs. METHODS: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues. RESULTS: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05). CONCLUSIONS: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.

The mediating role of psychological flexibility in the relationship between psychotic symptom severity and depression in individuals diagnosed with schizophrenia.

WHAT IS KNOWN ABOUT THE SUBJECT?: Psychotic symptoms and depression are common problems in people diagnosed with schizophrenia. Psychological flexibility is a skill that facilitates coping with difficulties. There is limited research on the role of psychological flexibility in the relationship between psychotic symptoms and depression in people diagnosed with schizophrenia. WHAT DOES THE ARTICLE ADD TO EXISTING KNOWLEDGE?: This article investigates the role of psychological flexibility in the link between psychotic symptom severity and depression in people diagnosed with schizophrenia. The article shows that psychological flexibility partially mediates the relationship between psychotic symptom severity and depression. The article suggests that interventions aimed at improving psychological flexibility may be beneficial in reducing depressive symptoms in people diagnosed with schizophrenia. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses should consider psychotic symptom severity and psychological flexibility when assessing and intervening for depressive symptoms in people diagnosed with schizophrenia. Mental health nurses should receive training to improve psychological flexibility and pass this skill on to their patients. Mental health nurses should continue to research the effectiveness and outcomes of interventions aimed at improving psychological flexibility. ABSTRACT: INTRODUCTION: Psychological flexibility may help people diagnosed with schizophrenia (PWS) cope with their psychotic symptoms and reduce their depressive symptoms, but the mechanism of this effect is unclear. AIM: To investigate whether psychological flexibility mediates the relationship between psychotic symptom severity and depression in PWS. METHOD: A cross-sectional study was conducted, in which a total of 111 PWS were assessed with DSM-5 Clinician-Rated Dimensions of Psychosis Symptom Severity, Calgary Depression Scale for Schizophrenia and Acceptance and Action Questionnaire. Data analysis was performed using SPSS 25 and PROCESS macro. RESULTS: Significant correlations were found between psychotic symptoms, depression and psychological flexibility. Psychological flexibility partially mediated the relationship between psychotic symptom severity and depression. DISCUSSION: Psychological flexibility could weaken the impact of psychotic symptom severity on depression in PWS. Higher psychotic symptoms were associated with lower psychological flexibility and higher depression. IMPLICATIONS FOR PRACTICE: Interventions to improve psychological flexibility may prevent depressive symptoms in PWS. Psychiatric nurses can use psychological flexibility as a goal for evaluation and intervention.

Comparison of Inflammatory Marker Scoring Systems and Conventional Inflammatory Markers in Patients over 65 Years of Age Admitted to the Intensive Care Unit: A Multicenter, Retrospective, Cohort Study.

Background: The aim of the current study is to evaluate the effects of inflammation markers on infection and mortality in patients over 65 years of age monitored in the intensive care unit (ICU). In this study, we attempted to determine the significance of the pan-immune-inflammation value (PIV); the neutrophil-lymphocyte ratio (NLR); the platelet-lymphocyte ratio (PLR); the monocyte-lymphocyte ratio (MLR); the systemic immune-inflammatory index (SII); the systemic immune response index (SIRI); multi-inflammatory indices (MIIs) 1, 2, and 3; and the CRP/albumin ratio (a new biomarker) as prognostic and mortality markers in patients over 65 years of age being monitored in the ICU. Methods: This multicenter, retrospective, cohort study was conducted on patients aged 65 and over who were admitted to two tertiary-level ICUs. Patients with cirrhosis, bone marrow transplantation, hematologic malignancy, steroid intake, current chemotherapy treatment, and neutropenia upon admission to the ICU were excluded from this study. Results: A total of 333 patients were included in this study. The group's 28-day mortality was found to be 31.8%. When each inflammatory marker associated with 28-day mortality was examined, the CRP/albumin ratio was found to be a better indicator than both the NLR and the SIRI, and the results were statistically significant (AUC: 0.665, 95% CI: 0.604-0.726, and p < 0.001). The NLR showed moderate discriminative ability in distinguishing mortality risk (AUC: 0.593, 95% CI: 0.526-0.660, and p = 0.006). Although the SIRI was lower than the NLR, it produced a statistically significant result (AUC: 0.580, 95% CI: 0.514-0.646, and p = 0.019). The CRP/albumin ratio was the most effective inflammatory marker in predicting mortality risk in older patients admitted to the ICU. Conclusions: It is important to monitor inflammatory markers (especially CRP/albumin ratio, NLR, SIRI, and MII 1-2-3) in older patients admitted to the ICU in order to accurately predict 28-day mortality. In the current study, the effects of PIV, MLR, PLR, and SII on the prediction of 28-day mortality in older ICU patients could not be demonstrated. We believe that more clinical studies are needed to determine the effects of PIV, MLR, PLR, and SII on short- and long-term prognoses and survival in older ICU patients.

Impact of extracorporeal hemadsorption on mortality in critically ill COVID-19 patients in the intensive care unit.

BACKGROUND: The consequences of COVID-19, such as respiratory failure and mortality, require the search for fast and effective solutions. The aim of this retrospective study is to determine the effect of extracorporeal hemadsorption on mortality in severe COVID-19 cases hospitalized in the intensive care unit (ICU). METHODS: Our study is retrospective, single-center, and observational. The study included ICU patients diagnosed with COVID-19 who received extracorporeal hemadsorption treatment between March 2020 and December 2020. Effects on mortality were examined by comparing pre- and post-hemadsorption values. RESULTS: Seventeen patients were included in the study. The mortality rate in the study was 64.7%. After hemadsorption, an increase was observed in the lymphocyte numbers, APACHE-II, and SOFA values of the patients (p = 0.026, 0.043, and 0.033; respectively). A significant decrease was observed in CRP and fibrinogen levels (p = 0.003 and 0.005; respectively). In the non-surviving patient group, APACHE-II, SOFA, and procalcitonin values were found to be high before and after the procedure (p = 0.002, 0.048, and 0.06; respectively). CONCLUSION: In COVID-19 patients, APACHE-II and SOFA scores may be useful in predicting the effectiveness of extracorporeal hemadsorption. Our study found that patients with higher APACHE-II and SOFA scores at baseline had a higher mortality rate after hemadsorption. These findings show that the use of intensive care scoring systems may be useful in determining which patients should receive extracorporeal hemadsorption and that hemadsorption should be performed in the early stages of the disease.

Internalized stigma and traumatizing effects of psychiatric hospitalization in adolescents: Is there any difference between being hospitalized in adult or adolescent inpatient psychiatric services?

OBJECTIVE: Psychiatric hospitalization serves as a critical treatment modality. However, hospitalization may pose risks of traumatization or stigma. This study primarily examined the internalized stigma and traumatizing effects of psychiatric hospitalization on adolescents. Additionally, the treatment of adolescents within adult inpatient psychiatric services may yield differing stigmatization and posttraumatic stress disorder (PTSD) symptomatology. Hence, the secondary objective was to discern the variance in stigmatization and PTSD symptoms between adolescents treated in adult inpatient psychiatric services (AIPS) and those in child and adolescent inpatient psychiatric services (CAIPS). METHOD: The cohort consisted of patients from Akdeniz University's Adult Psychiatry Inpatient Service (n = 29) and Uludag University's Child and Adolescent Psychiatry Inpatient Service (n = 28), matched for age and gender. Assessments using the Child Posttraumatic Stress Disorder-Reaction Index and the Internalized Stigma Scale for Children and Adolescents (ISSCA) were conducted 6 months after discharge. RESULTS: 36.8% and 10.5% of adolescents exhibited "mild" and "very severe" PTSD symptoms, respectively. Adolescents treated in CAIPS had higher Child Posttraumatic Stress Disorder-Reaction Index scores than those in AIPS. However, there was no significant difference between the AIPS and CAIPS groups regarding ISSCA-self and ISSCA-perceived scores. CONCLUSIONS: The current findings underscore that psychiatric hospitalization can lead to traumatic experiences in adolescents, especially those treated in CAIPS. Providing informed care and emotional support during hospitalization could bolster resilience and facilitate recovery among these individuals. While adolescents are sometimes placed in AIPS, it is crucial that professionals are adequately trained and supported in managing this vulnerable population. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Screening for Patients with Mild Alzheimer Disease Using Frequency Doubling Technology Perimetry.

We compared the visual field performances of patients with mild Alzheimer disease (AD) with normal subjects and detected visual field impairment attributable to the magnocellular pathway using frequency doubling technology-Matrix (FDT-Matrix). We recruited 43 patients with mild AD (mean age: 68.0 ± 7.2 years) and 33 controls who are visually and cognitively normal (mean age: 64.1 ± 6.4 years). All participants had at least two reliable FDT-Matrix 30-2 tests. Reliability indices, global indices (mean deviation and pattern standard deviation), and glaucoma hemifield test results were measured with FDT-Matrix. The mean test duration was significantly longer in patient group compared with controls (p = 0.002). Among the reliability indices, false negatives were higher in patient group than controls (p = 0.003). There were statistically significant differences in mean deviation and pattern standard deviation values (p < 0.0001 and p < 0.0001, respectively) and glaucoma hemifield test results (p < 0.001) between the patient and the control group. Our results imply that the pathogenesis of cognitive deterioration may not only be confined to the cortical area but also to the magnocellular pathway. We underline that FDT testing can be useful for the identification of early impairment and the follow-up of patients with AD.

Clitocybe nebularis extract and 5­fluorouracil synergistically inhibit the growth of HT-29 colorectal cancer cells by inducing the S phase arrest.

Although 5-fluorouracil (5-FU) is an important anticancer agent for the treatment of colorectal cancer, drug resistance, and dose-related side effects limit the effectiveness of the treatment. Therefore, developing new pharmaceuticals with effective and low toxicity is critically necessary for cancer therapy. This study aimed to investigate the cytotoxic activity of the Clitocybe nebularis mushroom extract (CN) on HT-29 human colon cancer cells. A series of in vitro experiments were performed on the HT-29, Caco-2, and HEK-293 cells, which includes cytotoxicity, drug interaction, colony formation, cell cycle, and migration assays. In addition, qRT-PCR experiment was also performed to investigate the potential molecular mechanisms of action of CN on the proliferation of colon cancer cell line. Our results show that CN exhibited selective cytotoxic activity on HT-29 and Caco-2 colon cancer cells, whereas no cytotoxic effect was observed on normal HEK-293 cells. With the combination of CN and 5­FU, their cytotoxic activity on HT-29 cells was significantly increased compared to their use alone. In addition, the combination of CN and 5-FU also showed synergistic anticancer activity through cell cycle arrest in the S phase. The results also show that p21, p27, and p53 expression levels increased as a result of CN treatment. Our in vitro findings show that CN has a synergistic effect with 5-FU by inhibiting cell proliferation of colon cancer cells and inducing cell cycle arrest in the S phase.

Multigene Panel Testing in Turkish Hereditary Cancer Syndrome Patients.

Objective: Hereditary cancer syndromes (HCSs) are a heterogenous group of disorders caused by germline pathogenic variations in various genes that function in cell growth and proliferation. This study aimed to describe the germline variations in patients with hereditary cancer using multigene panels. Methods: The molecular and clinical findings of 218 patients with HCS were evaluated. In addition, 25 HCS-related genes were sequenced using a multigene panel, and variations were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. In total, 218 HCS patients predominantly with breast, colorectal, ovarian, gastric, and endometrium cancers were included. Results: Pathogenic variations in 12 distinct genes were detected in 36 of 218 (16.5%) cases. In this study, the most affected gene was the ATM gene, in which pathogenic variations were detected in 8 of 218 cases, followed by CHEK2 (3.2%), MUTYH (3.2%), BRIP1 (1.8%), BARD1 (0.9%), TP53 (0.9%), PALB2 (0.4%), MLH1 (0.4%), MSH2 (0.4%), PMS2 (0.4%), RAD50 (0.4%), and RAD51C (0.4%). Conclusions: This study contributes to genotype-phenotype correlation in HCSs and expands the variation spectrum by introducing three novel pathogenic variations. The wide spectrum of the gene pathogenic variations detected and the presence of multiple gene defects in the same patient make the multigene panel testing a valuable tool in detecting the hereditary forms of cancer and providing effective genetic counseling and family specific screening strategies. Amaç: Herediter kanser sendromlari (HCS) hücre büyümesi ve proliferasyonunda görevli genlerde saptanan germline mutasyonlardan kaynaklanan heterojen bir grup hastaliktir. Bu çalismada kalitimsal kanser sendrom ön tanisiyla degerlendirilen olgularda çoklu gen paneli ile germ hatti varyasyonlarinin degerlendirilmesi planlanmistir. Yöntemler: Kalitimsal kanser sendromu düsünülen 218 olgudan periferik kandan DNA izolasyonu sonrasi HCS ile iliskili 25 gen multigen panel kullanilarak dizilendi ve varyasyonlar American College of Medical Genetics and Genomics (ACMG) kriterlerine göre degerlendirildi. Bulgular: Meme, kolorektal, over, gastrik ve endometriyum kanseri basta olmak üzere toplam 218 herediter kanser sendromlu olgu degerlendirildi. Tüm çalisma grubu incelendiginde en sik ATM gen varyasyonlari (8/218, %3,6) tespit edildi ve bunu siklik sirasina göre CHEK2 (%3,2), MUTYH (%3,2), BRIP1 (%1,8), BARD1 (%0,9), TP53 (%0,9), PALB2 (%0,4), MLH1 (%0,4), MSH2 (%0,4), PMS2 (%0,4), RAD50 (%0,4), RAD51C (%0,4) varyasyonlari takip etmekteydi. Sonuçlar: Bu çalismada farkli kanser türlerinde kalitimsal kansere yol açan genler analiz edilmis ve fenotiple iliskisi degerlendirilmistir. Ayrica bu çalismada ilk kez saptanan üç yeni varyasyon ile literatüre katki saglanmaktadir. Patojenik varyasyon tespit edilen genlerin genis dagilimi ve ayni hastada birden fazla genetik varyasyonun varligi düsünüldügünde, uygun genetik danisma ve aileye özgü tarama planlamasi yapmak için çoklu gen taramasi kalitimsal kanser hastalarinin degerlendirilmesinde hizli ve etkin bir yöntem olarak görünmektedir.

Selective laser trabeculoplasty induced changes in the thickness of ciliary body and iris evaluated by ultrasound biomicroscopy.

BACKGROUND: Selective laser trabeculoplasty (SLT) is widely used for the treatment of glaucoma. The main target tissue of this treatment modality is trabecular meshwork. We aimed to detect the SLT-induced changes in the thickness of ciliary body (CBT) and iris (IT), quantitatively. METHODS: Thirty-one patients treated by SLT were examined by ultrasound biomicroscopy (UBM) at different locations of ciliary body and iris at four quadrants, before and after (3rd, 7th, and 30th days) SLT. The IT was measured at various locations; 500 µm anterior to the scleral spur (IT(1)), 2 mm from the iris root (IT(2)) and near the pupillary edge where the iris thickness was maximum (IT(3)) at four quadrants. The CBT at positions 1 and 2 mm posterior to the scleral spur were measured (CBT(1-2)). Additionally, intraocular pressure (IOP) levels were measured in all visits and post-laser 1 h. RESULTS: There were statistically significant higher CBT values at 3rd and 7th-day measurements in the study compared to pre-treatment levels (p < 0.0001, p < 0.0001, respectively). CBT(2) values at day 30 were similar compared to pre-treatment values (overall p = 0.140), but CBT(1) values at day 30 were not exactly similar compared to pre-treatment values in superior and nasal quadrants (overall p = 0.027). IT values obtained in the 3rd and 7th days were significantly higher in all quadrants and regions when compared to the pre-treatment values (p < 0.0001, p < 0.0001, respectively). There were no statistically significant differences in any of the IT values at the 30th day in comparison to the pre-treatment values (p = 0.45). CONCLUSIONS: The results suggest that SLT induces prominent increases in CBT and IT returning to baseline thickness in a month, which may be caused by inflammation, vascular engorgement, or mechanical muscular contraction.

The Remarkable Antibiofilm Activity of the Sweet Tooth Mushroom, Hydnum repandum (Agaricomycetes), Displaying Synergetic Interactions with Antibiotics.

This study examines the antioxidant, anticancer, antimicrobial, and antibiofilm activities of Hydnum repandum, an edible and medicinal mushroom known as sweet tooth or wood hedgehog. H. repandum ethanolic extract had a high amount of myricetin and apigenin and displayed antiproliferative effects against the MCF-7 and HT-29 cell lines. Moreover, the extract displayed antimicrobial and antibiofilm activities against methicillin-resistant Staphylococcus aureus ATCC 43300, S. epidermidis ATCC 35984, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853. Synergetic interactions have been observed when antibiotics such as kanamycin and ampicillin are used together with mushroom extract. The minimum biofilm eradication concentration values were lower for H. repandum extract than for antibiotics. This study demonstrates that H. repandum has antibiofilm potential against biofilms and confronts antibiotic resistance.