Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype

LIMPRINT study - the Turkish experience

Background: Lymphedema and chronic oedema is a major healthcare problem in both developed and non-developed countries The LIMPRINT study is an international health service based study to determine the prevalence and functional impact in adult populations of member countries of the International Lymphoedema Framework (ILF). Methods: 1051 patients from 8 centers in Turkey were recruited using the LIMPRINT study protocol. Data were collected using the core and module tools which assess the demographic and clinical properties as well as disability and QoL. Results: Most of the Turkish patients were recruited from specialist lymphedema services and were found to be female, housewives and having secondary lymphedema due to cancer treatment. The duration of lymphedema was commonly less than 5 years and most of them had ISL Grade 2 lymphedema. Cellulitis, infection and wounds were uncommon. The majority of patients did not get any treatment or advice before. Most of the patients had impaired QoL and decreased functionality, but psychological support was neglected. Although most had social health security access to Lymphedema centres nevertheless access seemed difficult due to distance and cost. Conclusion: The study has shown the current status and characteristics of lymphedema patients, treatment conditions, the unmet need for the diagnosis and treatment as well as burden of the disease in both patients and families in Turkey. National health policies are needed for the prevention, diagnosis and treatment in Turkey that utilise this informative data

Üst Trapez Kasındaki Miyofasiyal Ağrı Sendromunda Tetik Noktaların Klinik Bulgular, Algometre ve Ultrasonografi ile Değerlendirilmesi: Yaşam Kalitesi ile İlişkisi

Introduction: Myofascial pain syndrome (MPS) which is the leading cause of musculoskeletal pain, is experienced at any time in 85% of the general population. MPS disrupts the quality of life and functionality. The aim of this study was to determine the severity of the pain at the trigger points by visual analog scale (VAS) and algometer, and to evaluate the relationship between the patients’ functional status and quality of life, as well as to investigate the correlation between the quantitative USG measurements and clinical variables, in patients with MPS. Materials and Methods: A total of 88 patients with MPS who were aged between 18-60 years and who had been admitted to Hacettepe University Department of Physical Medicine and Rehabilitation, were included to the study. Age, gender, duration of symptoms, education, height, weight, body mass index were recorded. Physical examination was performed to determine the number of trigger points and range of motion of the neck. The pressure pain threshold at the most painful trigger point was measured by the algometer; the same point was evaluated by shear-wave elastography. Patients completed the visual analog scale (VAS), Neck Pain and Disability Index (NPDI), Nottingham Health Profile (NHP). Results: Seventy-eight (89%) of the patients were female and 10 (11%) were male. The mean age was 33.6 ± 11.8 years. VAS scores were moderately correlated with NPDI scores and as well as with the first/second parts of the NHP. There was no correlation between the duration of symptoms and the number of trigger points with VAS score, pressure pain threshold and shar-wave elastography variables. No correlation was observed between shear-wave elastography velocity measurements and other clinical variables. Conclusion: The severity of pain in MPS patients was correlated with functional status and quality of life, but no correlation was observed between ultrasonographic measurements and clinical variables. In recent years, ultrasonographic evaluation of musculoskeletal problems is very important. Further research is required in order to determine the relationship between ultrasonographic measurements and severity of pain, functional status and quality of life and also to suggest the shear-wave elastography in the diagnosis and treatment follow-up of patients with MPS.Giriş: Kas iskelet sistemi ağrılarının önde gelen nedeni olan MAS, genel popülasyonun %85’inde hayatının herhangi bir noktasında yaşanmaktadır. Yaşam kalitesini ve fonksiyonelliği bozmaktadır. Çalışmanın amacı miyofasiyal ağrı sendromunda tetik noktalardaki ağrının şiddetini vizüel analog skala (VAS) ve algometre ile belirlemek, hastanın fonksiyonel durumu ve yaşam kalitesi ile ilişkini değerlendirmek, kantitatif bir yöntem olan USG (shear-wave elastografi) ölçümleri ile korelasyonunu incelemektir. Gereç ve Yöntem: Hacettepe Üniversitesi Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı polikliniğine başvuran, 18-60 yaş arası, 3 aydan uzun süreli miyofasiyal ağrı sendromu kliniği olan kognitif durumu iyi, 88 hasta çalışmaya dahil edildi. Hastaların yaşı, cinsiyeti, semptomların süresi, eğitim durumları, boy, kilo, vücut kitle indeksi, sorgulanarak kaydedildi. Fizik muayene ile tetik nokta sayısı belirlendi, boyun eklem hareket açıklığı ölçümü yapıldı. En ağrılı tetik noktada basınç ağrı eşiği algometre ile ölçüldü; yine aynı nokta ultrasonografik elastografi ile incelendi. Hastalarda ağrının şiddeti VAS ile, fonksiyonel durum Boyun Ağrı ve Özürlülük Skalası’yla (BAÖS), yaşam kalitesi ise Nottingham Sağlık Profili (NSP) ile değerlendirildi. Bulgular: Hastaların 78’i (%89) kadın, 10’u (%11) erkekti. Yaş ortalaması 33,6 ±11,8 yıl olarak bulundu. Çalışmamızda VAS skoru ile BAÖS ve NSP birinci/ikinci bölümleri arasında orta düzeyde korelasyon saptandı. Semptomların süresi ve tetik nokta sayısı ile VAS skoru, basınç ağrı eşiği (BAE), shear-wave elastografi hızı arasında ilişki izlenmedi. Shear-wave elastografi hızı ölçümleri ile fonksiyonel durum ve yaşam kalitesi skorları arasında ilişki saptanmadı. Sonuç: MAS tanılı hastalarda ağrı şiddeti ile fonksiyonel disabilite ve yaşam kalitesi arasında anlamlı ilişki mevcuttur. Ancak ultrasonografik ölçümlerle klinik değişkenler arasında ilişki gösterilememiştir. Son yıllarda kas iskelet sistemi sorunlarında önemli yer edinen ultrasonografik incelemelerle MAS tanılı hastalardaki ağrı, fonksiyonel durum ve yaşam kalitesi arasındaki ilişkinin belirlenmesi ve shear-wave elastografinin MAS tanı ve tedavi takibinde önerilmesi için ileri çalışmalar gerekmektedir

Quartz Crystal Microbalance Based Histidine Sensor

Herein, quartz crystal microbalance (QCM) biosensor is prepared for the detection of L-histidine by attachment of L-histidine imprinted poly(EGDMA-MAH/Cu(II)) nanoparticles on QCM electrode. The imprinted nanoparticles with the size of 86.43 nm were synthesized via miniemulsion polymerization reaction. Prepared QCM sensors were characterized with ellipsometer, contact angle measurements and FTIR. The thickness measurements demonstrated that the particle thin films were almost mono-layer. L-histidine solutions with a concentration range between 6.44 mu M and 225.6 mu M were introduced to QCM system to determine the adsorption kinetics. Selectivity of the L-histidine imprinted nanoparticles were examined using D-histidine and L-tryptophan as competitor molecules. L-histidine imprinted QCM biosensors was also used for RNAase, lysozyme, cytochrome-C and BSA to investigate the competitive adsorption of surface histidine exposed proteins.WoSScopu

The Reliability And Validity Of Lymphedema Quality Of Life Questionnaire-Arm In Turkish Patients With Upper Limb Lymphedema Related With Breast Cancer

Objectives: This study aims to adapt Lymphedema Quality of Life Questionnaire-Arm (LYMQOL) into Turkish and to test its reliability and validity in Turkish patients with upper limb lymphedema related with breast cancer. Patients and methods: Between June 2015 and November 2015, the Turkish LYMQOL-Arm was obtained using forward-backward translation method and administered to a total of 135 female patients (mean age 51.8 +/- 9.8 years; range, 31 to 82 years) with upper limb lymphedema with European Organization for Research and Treatment of Cancer-QoL Breast Cancer-specific version (EORTC QLQ-BR23) and Functional Assessment of Cancer Therapy-Breast-4 (FACT-B+4) questionnaires. A test-retest interval of seven-days was used to assess the reliability. The validation studies were carried-out by means of construct-validity using Spearman's rank correlation-coefficient. Internal consistency and test-retest-reliability were assessed using Cronbach's alpha and intra-class correlation-coefficient (ICC), respectively. Results: 135 patients completed the questionnaire with upper limb lymphedema related with breast cancer completed the questionnaires. The mean lymphedema duration was 21.1 +/- 28.7 (median: 6) months. Internal consistency and reliability of the Turkish LYMQOL-Arm was good with Cronbach's alpha (0.88-0.90) and test-retest ICC (0.45-0.71). External construct validity was highly confirmed by expected correlations with comparator scales, EORTCQLQ-BR23 and FACT-B+4 (p<0.01). Conclusion: The Turkish version of the LYMQOL-Arm is a valid and reliable tool for evaluating QoL in female patients with upper limb lymphedema related with breast cancer.WoSScopu

Preparation of molecular imprinted injectable polymeric micro cryogels for control release of mitomycin C

In this work, microscale poly-2-hydroxyethyl methacrylate [p(HEMA)]-based cryogels were fabricated as a drug delivery material using molecular imprinting technology for controlled release of mitomycin C (MMC) as an anti-cancer drug. MMC imprinted pHEMA-based micro cryogels (pMIPs) were prepared according to free-radical polymerization by using N-methacryloyl-(l)-histidine methyl ester (MAH) as an amino-acid-based polymerizable functional monomer using a micro stencil array chip with microwells of 200 μm diameter and 500 μm thickness. Following that, scanning electron microscope, swelling test, and Fourier Transform Infrared Spectroscopy were used for the characterization studies of pMIPs. After the characterization studies, MMC release performance of pMIPs was investigated towards the different pH values and various MMC concentrations in the aqueous solutions. The in vitro cytotoxicity studies of the pMIPs and the non-imprinted pHEMA based micro cryogels (pNIPs) were examined using L929 cell line. According to the experimental findings, the incorporation of MAH monomer could increase the release performance of pMIPs and the release of MMC from the pMIPs was non-Fickian in the aqueous solution. pMIPs did not show any noticeable cytotoxicity and could be potentially used as a new drug carrier for MMC release

Injectable cryogels in biomedicine

Cryogels are interconnected macroporous materials that are synthesized from a monomer solution at sub-zero temperatures. Cryogels, which are used in various applications in many research areas, are frequently used in biomedicine applications due to their excellent properties, such as biocompatibility, physical resistance and sensitivity. Cryogels can also be prepared in powder, column, bead, sphere, membrane, monolithic, and injectable forms. In this review, various examples of recent developments in biomedical applications of injectable cryogels, which are currently scarce in the literature, made from synthetic and natural polymers are discussed. In the present review, several biomedical applications of injectable cryogels, such as tissue engineering, drug delivery, therapeutic, therapy, cell transplantation, and immunotherapy, are emphasized. Moreover, it aims to provide a different perspective on the studies to be conducted on injectable cryogels, which are newly emerging trend

Hypermobility Frequency in School Children: Relationship With Idiopathic Scoliosis, Age, Sex and Musculoskeletal Problems.

This study aims to assess the prevalence of generalized joint hypermobility (GJH) in school children in relation to scoliosis and to identify musculoskeletal problems

Hypermobility Frequency in School Children: Relationship With Idiopathic Scoliosis, Age, Sex, and Musculoskeletal Problems

Objectives: This study aims to assess the prevalence of generalized joint hypermobility (GJH) in school children in relation to scoliosis and to identify musculoskeletal problems. Patients and methods: This cross-sectional study included 822 school children (413 males, 409 females; mean age 12.2 +/- 1.3 years; range, 10 and 15 years). Demographic characteristics of all children were recorded. The presence of GJH was assessed by the Beighton score (>= 4 was considered joint hypermobility). Scoliosis screening consisted of forward bend test (FBT) and measurement of angle of trunk rotation (ATR). Positive FBT or ATR was >= 5 degrees referred to a portable X-ray device. The presence of musculoskeletal complaints was determined by a questionnaire. Results: Children's body mass index (BMI) was 19.6 +/- 4.1. GJH was diagnosed in 151 subjects (18.4\%). No significant association was detected between sex and hypermobility. Joint hypermobility was inversely correlated with age and BMI. Scoliosis was found in 43 subjects (5.2\%) and all of them except one girl had mild scoliosis. The most common scoliosis pattern was a single left thoracolumbar curve. Seventy-three subjects (8.9\%) had Cobb angle under 10 degrees, with a potential for progression. Among subjects having GJH, the most common clinical finding was pes planus (34.3\%) and the most common clinical symptom was ankle sprain 31.3\%). Conclusion: Similar to that found in children from many countries, GJH is a common clinical condition in Turkish children. GJH should be assessed in the differential diagnosis of adolescents with musculoskeletal complaints for effective treatment and reducing morbidity. GJH should be considered in adolescents with scoliosis, which may be an important aspect treatment

Exosomal miRNA confers chemo resistance via targeting Cav1/p-gp/M2-type macrophage axis in ovarian cancerResearch in context

Background: Circulating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood. Methods: To investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model. We showed the effect of OC exosomal miR-1246 uptake on macrophages by co-culture experiments. Findings: Substantial expression of oncogenic miR-1246 OC exosomes was found. We showed that Cav1 gene, which is the direct target of miR-1246, is involved in the process of exosomal transfer. A significantly worse overall prognosis were found for OC patients with high miR-1246 and low Cav1 expression based on TCGA data. miR-1246 expression were significantly higher in paclitaxel-resistant OC exosomes than in their sensitive counterparts. Overexpression of Cav1 and anti-miR-1246 treatment significantly sensitized OC cells to paclitaxel. We showed that Cav1 and multi drug resistance (MDR) gene is involved in the process of exosomal transfer. Our proteomic approach also revealed that miR-1246 inhibits Cav1 and acts through PDGFβ receptor at the recipient cells to inhibit cell proliferation. miR-1246 inhibitor treatment in combination with chemotherapy led to reduced tumor burden in vivo. Finally, we demonstrated that when OC cells are co-cultured with macrophages, they are capable of transferring their oncogenic miR-1246 to M2-type macrophages, but not M0-type macrophages. Interpretation: Our results suggest that cancer exosomes may contribute to oncogenesis by manipulating neighboring infiltrating immune cells. This study provide a new mechanistic therapeutic approach to overcome chemoresistance and tumor progression through exosomal miR-1246 in OC patients. Keywords: Exosome, oncomiR, miR-1246, Ovarian cancer, Cav1, P-g