bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-143 as a new weapon against cancer: overview of the mechanistic insights and long non-coding RNA mediated regulation of miRNA-143 in different cancers
Authors: Farooqi Ammad Ahmad , Qureshi Muhammad Zahid , Attar Rukset , Alhewairini Saleh S , Fayyaz Sundas , Sabitaliyevich Uteuliyev Yerzhan , Duisenbayevich Tuyebakhov Meirzhan , Alaaeddine Nada
Published: August 2019

Central dogma of molecular biology, a term coined by Francis Crick in 1958 was considered to be the cornerstone of molecular biology unless molecular biologists challenged the idea after ground-breaking discovery of non-coding RNAs. Discovery of microRNAs marked a new era and revolutionized our understanding related to puzzling mysteries about intermediate steps between transcription and translation. Technological advancements have spawned a multitude of platforms for profiling of long-noncoding RNAs and miRNAs in different cancers. Detailed investigation of mRNA targets of miRNAs has enabled high-order analyses of interconnected networks and revealed affected pathways in different cancers. miR-143 has emerged as a multi-talented tumor suppressor microRNA having considerable ability to inhibit and prevent cancer via regulation of myriad of oncogenes. In this review, we will summarize most recent evidence related to characteristically unique ability of miR-143 to target different oncogenic mRNAs in different cancers. We will also comprehensively discuss how scientists have identified multiple long non-coding RNAs reportedly involved in promoting the expression of oncogenes by interfering with miR-143 mediated targeting of these oncogenes. Because of excellent ability of miR-143 to effectively target oncogenic mRNAs, researchers have started to focus on use of miR-143 mimics to restore expression of miR-143 in various cancers.
Analysis of serum cfDNA concentration and integrity before and after surgery in patients with lung cancer
Authors: Fan Yihui , Shi Minxin , Chen Saihua , Ju Guanjun , Chen Lingxiang , Lu Haimin , Chen Jian , Zheng Shiying
Published: August 2019

The content and integrity of cell-free DNA (cfDNA) before and after surgery in patients with lung cancer were determined to investigate its clinical significance.   Peripheral blood was collected from 120 patients with lung cancer who were treated in our hospital from March 2016 to November 2018, including 50 cases before operation and 70 cases after operation. 60   healthy subjects served as controls. Quantitative PCR was used to determine the cfDNA level of each group. The relationship between cfDNA levels and the clinical features of lung cancer patients was determined. Receiver Operating Curves were used to determine the sensitivity and specificity of cfDNA, CEA, NSE and CYFRA21-1 in lung cancer.  The concentration and integrity of cfDNA before surgery in patients with lung cancer were significantly higher than those after surgery and those in healthy control group. The cfDNA concentration in patients with lung cancer after surgery was significantly higher than that in the control group, but there was no statistical difference in cfDNA integrity between the two groups. There was no significant correlation between cfDNA concentration/integrity and gender, age, tumor type, tumor stage, and expressions of CA199, CA125, and CA153 in patients with lung cancer before or after surgery. However, there were significant correlations between the expression levels of CEA, NSE, and CYFRA21-1 and cfDNA concentration. The expression levels of CEA and CYFRA21-1 were significantly correlated with cfDNA integrity before surgery, while the correlations were not significant after surgery.  The concentration and integrity of cfDNA increased significantly in serum of lung cancer patients. The concentration and integrity of cfDNA in patients with lung cancer after surgery were significantly lower than those before surgery. Thus, cfDNA has high application value in the diagnosis and evaluation of lung cancer.
Clinical value of plasma cfDNA concentration and integrity in breast cancer patients
Authors: Miao Yajun , Fan Yingrui , Zhang Liang , Ma Tingting , Li Rong
Published: August 2019

Breast cancer is a malignant tumor that occurs in the glandular epithelial tissues of the breast. It is one of the most common malignant tumors in women. This study was aimed at investigating the role of cell-free DNA (cfDNA) as a potential biomarker for breast cancer diagnosis. Patients with primary breast cancer (n =110) were enrolled in the experimental group, 95 patients with benign breast tumors were in control group 1, while 90 healthy volunteers were in control group 2. Quantitative PCR was used to determine cfDNA concentration and integrity in each group. The cfDNA levels in different groups and their relationship with clinical features of breast cancer patients were analyzed. Receiver operational curves were established to analyze sensitivity and specificity of cfDNA concentration, cfDNA integrity, CEA, CA125 and CA15-3. The cfDNA concentration and cfDNA integrity of the experimental group were significantly higher than those of control groups 1 and 2. The cfDNA concentration and integrity in plasma of experimental group after chemotherapy were significantly lower than those before chemotherapy. While CEA and CA15-3 expressions were significantly correlated with cfDNA concentration, CA125 expression was significantly correlated with cfDNA integrity. Results from ROC curve analysis showed that the sensitivity and specificity of cfDNA concentration and integrity were higher than those of traditional tumor biomarkers. These results indicate that cfDNA concentration and integrity are significantly higher in primary breast cancer patients than in benign breast tumor patients and healthy people. Thus, cfDNA may serve as a potential biomarker of breast cancer.
Molecular cloning and characterization of genes encoding chitinase and N-acetyl-Î²-glucosaminidase in Dolerocypris sinensis
Authors: Cheng Gong , Li Shaonan
Published: August 2019

Chitinases and N-acetyl-Î²-glucosaminidase (NAG) are important in molting and growth of crustaceans. In ostracods, the genes encoding these enzymes have not been characterized. The aim of the present study was to clone the genes encoding chitinase (DsChi) and NAG (DsNAG) from the ostracod, Dolerocypris sinensis, elucidate the phylogenetic relationships between the cloned genes and known chitinolytic enzymes, and determine the expression patterns of these genes at different stages of growth in the presence of an environmental pollutant. The genes were amplified from the genomic DNA of the organism using polymerase chain reaction (PCR). The products from PCR were cloned and characterized with bioinformatics tools, and their expression patterns at different growth stages were determined using real-time quantitative PCR (qRT-PCR). Nine and five introns were identified in DsChi and DsNAG genes, respectively. When compared with protein sequences available in GenBank, chitinase from D. sinensis was most closely related to that of Macrobrachium nipponense (61 % homology). The NAG of D. sinensis was most closely related to that of Limulus polyphemus (55.6 % homology). Based on phylogenetic analysis of known chitinases from crustaceans and insects, the D. sinensis chitinase tightly clustered in the same branch with chitinases from species within the Malacostraca class. In contrast, NAG of D. sinensis was clustered with NAG from F. candida.The level of expression of DsChi mRNA was significantly higher than that of DsNAG throughout the period of growth (p < 0.05). Treatment of D. sinensis cells with fenoxycarb significantly downregulated the expressions of DsChi and DsNAG throughout the period of growth (p < 0.05). These results show that the protein products of DsChi and DsNAG possess remarkable biochemical properties characteristic of a chitinase and NAG, respectively.
Antitumoral activity of Ficus carica L. on colorectal cancer cell lines
Authors: Soltana Hala , Pinon Aline , Limami Youness , Zaid Younes , Khalki Loubna , Zaid Nabil , Salah Driss , Sabitaliyevich Uteuliyev Yerzhan , Simon Alain , Liagre Bertrand , Hammami Mohamed
Published: August 2019

In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. In the present study we investigated the antitumor activity of Ficus carica extracts and latex. We evaluated the effects of increasing concentrations of Ficus carica extracts and latex on HCT-116 and HT-29 human colorectal cell proliferation using MTT assay and apoptosis induction by evaluating PARP cleavage by Western blot analysis. Peel, pulp, leaves, whole fruit and latex extracts of Ficus carica exerted significant antiproliferative effects on HCT-116 (IC50 values 239, 343, 177, 299, 206 µg/ml) and HT-29 cells (IC50 values 207, 249, 230, 261, 182 µg/ml) after 48h of treatment. Furthermore, treatment with different extracts of Ficus carica induced apoptosis in both HT-29 and HCT-116 cancer cells. Leaves and latex extracts of Ficus carica showed the strongest antiproliferative activities. Overall, our results showed that these natural products are strong apoptosis inducers which suggest their use of for therapeutic purposes.
Common SNP-based haplotype analysis of the 9p21.3 gene locus as predictor coronary artery disease in Tanzanian population
Authors: Akan Gokce , Kisenge Peter , Sanga Tulizo Shemu , Mbugi Erasto , Adolf Ismael , Turkcan Mehmet Kerem , Janabi Mohammed , Atalar Fatmahan
Published: August 2019

Genome-wide association studies (GWAS) have recently confirmed a strong association of the 9p21.3 locus with Coronary Artery Disease (CAD) in different populations but no data has been reported for the Tanzanian population. This study aimed to investigate the 9p21.3 locus harboring the disease-causing hotspot variations in Tanzanian CAD patients and their associations with the risk factors. 135 patients with CAD and 140 non-CAD patients were enrolled into the study. Further the biochemical analysis, the genotyping assays were performed by the use of qRT-PCR. The genotype and allele frequencies of rs1333049, rs2383207, rs2383206, rs10757274, rs10757278, and rs10811656 were significantly different between the groups (p<0.005). The genotype distribution of rs1333049, rs10757278 and rs10811656 polymorphisms were significantly different among patients with one, two, three stenotic vessels (p<0.05). For rs10757274 and rs10757278, the GG genotype indicated a significant 3-fold and 4-fold increased risk of CAD (p<0.0001,respectively). Additionally, haplotype analysis revealed that AAGCAG, AAACAG, GGGTGC haplotypes of 9p21.3 locus polymorphisms are associated with CAD risk. The GGGTGC haplotype was over-represented while the other two underrepresented in patients as compared to controls (p<0.00001,respectively) suggesting the first one a high-risk and the other two low-risk haplotypes for Tanzanian population. The AUC of a risk model based on non-genetic risk factors was 0.954 (95% CI: 0.930-0.977) and the combination with genetic risk factors improved the AUC to 0.982 (95% CI: 0.954-0.985) (p<0.012), indicating good diagnostic accuracy. Our results are the first data reporting statistically significant associations between 9p21.3 polymorphisms and CAD, and the very first haplotype block harboring the disease-causing variations in Tanzanian population.
Serum cell-free DNA concentrations and integrity analysis of colorectal cancer patients before and after surgery
Authors: Cao Guangxin , Xie Yu , Jiang Xiaohui , Tian Xiaofeng , Wang Ding , Sun Yan
Published: August 2019

This study was carried out to investigate cell-free DNA (cfDNA) as a potential biomarker for colorectal cancer diagnosis.Patients with colorectal cancer (n = 25) who had not undergone surgery, and 35 patients with postoperative colorectal cancer were enrolled. Peripheral blood samples were collected from the colorectal cancer subjects (experimental group), and also from 30 healthy volunteers (control group). Quantitative PCR (qPCR) was used to determine cfDNA concentration and integrity in each group. The cfDNA levels of the two groups were analyzed to determine the relationship between the cfDNA and the clinical features of colorectal cancer patients. The receiver operator curve (ROC) was used to analyze sensitivity and specificity of cfDNA, carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and cancer antigen 125 (CA125). cfDNA concentration and cfDNA integrity in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that of the healthy control group, but the integrity was not significantly different from the control group. There was no significant correlation between cfDNA concentration/integrity and gender, age, disease stage, tumor location, tumor differentiation, and expressions of cancer antigen 153 (CA153), neuron specific enolase (NSE) and alpha fetoprotein (AFP) in colorectal cancer patients before or after surgery. However, there was a significant correlation between the expression levels of CEA/CA125 and concentration of cfDNA. The CA199 expression level was significantly correlated with cfDNA integrity. The sensitivity and specificity of cfDNA and integrity were higher than those used for traditional tumor biomarker detection. cfDNA concentration is significantly increased in serum of colorectal cancer patients. Thus, it may serve as a potential indicator of colorectal cancer.
miR-532 promotes colorectal cancer invasion and metastasis by targeting NKD1
Authors: Song Xujun , Wu Rong , Tao Qingsong , Zhao Liangtao , Ji Zhenling
Published: August 2019

The aim of this study was to investigate the effect of microRNA-532 (miR-532) on invasion and metastasis of colorectal cancer (CRC) cells, and the underlying mechanism. Human CRC cell line (HCT116) and normal colon (FHC) cells were used for this study. The cells were transfected with naked cuticle homolog 1 (NKD1) overexpression plasmid, miR-532 mimics, miR-532 inhibitor or miR-532 non-homologous sequence using lipofectamine 2000. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of miR-532 in CRC cells, and a combination of scratch and Transwell assays was used to assess the effect of miR-532 on migration and invasion of CRC cells. Western blotting was used to determine the effect of miR-532 on NKD1 expression in CRC cells. Bioinformatics analysis and luciferase reporter gene assay were used to assess the regulatory effect of miR-532 on NKD1. The expression of miR-532 was upregulated in CRC cells relative to normal colon cells (p < 0.05). The HCT116 cells transfected with miR-532 mimics migrated faster than those of miR-532 negative control (miR532-NC) group (p < 0.05). The migration ability of HCT116 cells transfected with miR-532 inhibitor was significantly reduced, when compared with that of miR532-NC group (p < 0.05). The invasive ability of HCT116 cells transfected with miR-532 mimics was significantly higher than that of miR532-NC cells (p < 0.05). However, inhibition of miR-532 expression significantly reduced the invasive ability of HCT116 cells (p < 0.05). Results of bioinformatics showed that miR-532 had specific binding sequence with the 3'UTR region of NKD1. After cloning the sequence into the luciferase reporter plasmid, miR-532 significantly inhibited the expression of NKD1 (p < 0.05). However, miR-532 had no inhibitory effect on mutated NKD1 3'UTR (p > 0.05). Results of Western blotting showed that increased miR-532 expression significantly reduced the expression of NKD1, while decreased miR-532 expression promoted the expression of NKD1 (p < 0.05). Overexpression of NKD1 significantly down-regulated miR-532 overexpression and promoted CRC cell invasion and metastasis (p < 0.05). miR-532 is highly expressed in CRC cells and directly inhibits NKD1 expression, while enhancing invasion and metastasis of CRC cells. It promotes the development of CRC by inhibiting the expression of NKD1.
Evaluation of the usefulness of the simultaneous assay of fecal hemoglobin (Hb) and transferrin (Tf) in colorectal cancer screening – for the establishment of the Hb and Tf two-step cutoff assay (HTTC assay)
Authors: Hirata Ichiro
Published: August 2019

Background

One of the issues of fecal immunochemical test (FIT) is false-negativity caused by hemoglobin degradation by bacteria. We investigated the usefulness of the transferrin assay, which is stable toward bacteria.

Methods

The study included 1174 patients who visited our hospital and underwent colonoscopy for some symptoms or for cancer screening. We compared the hemoglobin-transferrin combination assay with the hemoglobin-alone assay using the Discrete Clinical Chemistry Analyzer NS-Plus and 1174 clinical samples. In the combination assay, two hemoglobin cutoff values (a) and (b) and one transferrin cutoff value (c) were set. Cases with values of (a) or more were defined as primary positive and values lower than (b) were defined as negative. Cases with values between (a) and (b) underwent the transferrin assay. Then, cases with values of (c) or higher were defined as secondary positive. All primary and secondary positive cases were defined as positive. Among the combination of cutoff values (a), (b) and (c), we identified Method A exhibiting high specificity and a positive predictive value (PPV), and Method B exhibiting the highest sensitivity.

Results

In Method A, the sensitivity of colorectal cancer detection increased from 67.3% to 68.2%, the specificity significantly (p = 0.0011) increased from 90.5% to 92.6%, and the PPV increased from 42.9% to 49.6% compared with the hemoglobin-alone assay. In Method B, the sensitivity increased significantly (p = 0.046) from 67.3% to 71.1% and the PPV increased from 42.9% to 44.8%.

Conclusions

This combination assay showed higher accuracy and effectiveness for colorectal cancer screening.
The selection of sealing technologies of the subsoil and hydrotechnical structures and quality assurance
Authors: Skutnik Zdzisław , Bajda Marek , Lech Mariusz
Published: August 2019

Various types of trenchless methods are extensively used to create engineering barriers for the purpose of achieving relatively low hydraulic conductivity of the subsoil and hydrotechnical structures. The most commonly used technologies of the grouting curtain creating are the DSM (Deep Soil Mixing), WIPS (Vibro Injcted Thin Wall), low-pressure injection and jet-grouting. Vertical barriers are widely used in environmental control systems to restrict the lateral spreading of liquid or gaseous contaminants and for seepage control through and beneath a levees. The barrier walls are constructed in a single or two phases using a slurry composed mainly of bentonite, cementitious materials and water. Often to solve complex geotechnical problems the technologies are combined (e.g. combining DSM and jet grouting). In the paper some examples of practical application of chosen types of technology dedicated different problems solving are presented. The results of geotechnical investigations of hydraulic permeability, shear strength and depth control of cut-off wall are given. The tests were carried out using BAT system, Cone Penetration Tests (CPT) and drillings. The presented test results should help define the technical and financial criteria that should be used to compare grouting based methods and other techniques applicable to the same geotechnical special works. These recommendations should permit an adequate application of grouting techniques and contribute to finding solutions for the delicate problem of ground sealing, notably when proceeding with hydrotechnical or environmental structures placed below water table.
Influence of long-term heat treatment of kraft black liquor on lignin precipitation and material properties
Authors: Pichler Thomas , Maitz Silvia , Kienberger Marlene
Published: August 2019

In the present study, the influence of long-term heat treatment of black liquor with focus on a subsequent lignin precipitation process was investigated. The well-known CO2 approach to precipitate a certain amount of lignin from heat-treated black liquor was studied within defined thermal conditions. Several important characteristics of lignin such as molar mass and functional groups were analysed. Viscosity and buffer capacity of black liquor were also studied. Results showed a reduction in lignin yield as a result of a decrease in molar mass and lignin demethylation after the heat treatment. The acid consumption during precipitation was found to be higher after the heat treatment.
Picture or non-picture? The influence of narrative task types on lower- and higher-proficiency EFL learners’ oral production
Authors: Qiu Xuyan
Published: August 2019

Picture-based storytelling tasks, i. e. telling a story relying on some pictures, and short speech tasks, i. e. producing a speech with a given topic without pictures, are two types of oral narrative tasks widely adopted in previous studies. However, few have discussed what effects these two types of tasks may exert on second language learners’ speaking performance. In this study, sixty English as a foreign language learners, divided into lower- and higher-proficiency groups, performed a picture-based storytelling task and a short speech task. Stimulated recalls were collected from seventeen participants. Their oral discourses were analysed in terms of complexity, accuracy, and fluency. Stimulated recalls were analysed based on Levelt’s speaking model. The short speech tasks raised participants’ accuracy and lexical complexity and were more effective for higher-proficient learners regarding structural complexity. The findings yield suggestions for designing oral narrative tasks for EFL learners with different L2 proficiency levels.
Grammatical aspect and world knowledge in second language reading
Authors: Kang Hyun-Sook , Kim Nayoung , Christianson Kiel
Published: August 2019

During normal reading, readers’ perceptions of time in a narrative shift according to grammatical and semantic cues. This study investigated the extent to which second-language (L2) readers’ interpretations of situations depicted in narratives are influenced by the grammatical aspect (perfective/progressive) and temporal duration (short/long) of intervening events. The study further examined whether reading fluency and L2 proficiency modulated how readers’ mentally constructed the depicted situations. Thirty-one L2 learners of English and 37 English-first-language (L1) controls completed a reading comprehension task in which each of 40 stories contained a target event with an inherent endpoint, with accomplishment verbs that were described as completed or in progress, followed by a short- or long-duration event. A reading-fluency task and a cloze test were administered. While grammatical marking played a significant role for both groups of participants, grammatical aspect and event duration showed an interaction only for L2 learners. The construction of a situation was modulated for both groups by reading fluency.
Random bases for coprime linear groups
Authors: Duyan Hülya , Halasi Zoltán , Podoski Károly
Published: August 2019

The minimal base sizeb⁢(G){b(G)}for a permutation groupGis a widely studied topic in permutation group theory. Z. Halasi and K. Podoski [Every coprime linear group admits a base of size two, Trans. Amer. Math. Soc. 368 2016, 8, 5857–5887] proved thatb⁢(G)≤2{b(G)\leq 2}for coprime linear groups. Motivated by this result and the probabilistic method used by T. Burness, M. W. Liebeck and A. Shalev, it was asked by L. Pyber [Personal communication, Bielefeld, 2017] whether or not, for coprime linear groupsG≤G⁢L⁢(V){G\leq GL(V)}, there exists a constantcsuch that the probability that a randomc-tuple is a base forGtends to 1 as|V|→∞{\lvert V\rvert\to\infty}. While the answer to this question is negative in general, it is positive under the additional assumption thatGis primitive as a linear group. In this paper, we show that almost all 11-tuples are bases for coprime primitive linear groups.
Triglyceride/glucose index is a reliable alternative marker for insulin resistance in South American overweight and obese children and adolescents
Authors: Locateli João Carlos , Lopes Wendell Arthur , Simões Caroline Ferraz , de Oliveira Gustavo Henrique , Oltramari Karine , Bim Ricardo Henrique , de Souza Mendes Victor Hugo , Remor Jane Maria , Lopera Carlos Andrés , Nardo Junior Nelson
Published: August 2019

Background

The aim of the present study was to investigate the correlation between the triglyceride/glucose index (TyG index) and homeostasis model assessment of insulin resistance (HOMA-IR). Additionally, we compared the ability of the TyG index and triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) index and the combination of these two indices (TyG index plus TG/HDL-c) to predict insulin resistance (IR) in South American overweight and obese children and adolescents.

Methods

A cross-sectional study was carried out in 345 overweight adolescents aged 10–18 years, from both the sexes. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL])/2, while the TG/HDL-c index was calculated by the division of TG (mg/dL) by HDL-c (mg/dL). HOMA-IR was calculated with the formula: fasting insulin (FI) (U/mL) × fasting glucose (mmol/L)/22.5. The cut-off point used to determine the presence of IR was HOMA-IR ≥ 3.16.

Results

The TyG index showed a positive correlation with HOMA-IR. The area under the receiver operating characteristic (ROC) curve of the TyG index was 0.74, indicating good sensitivity (75.7%) and specificity (67.4%). Furthermore, the TyG index cut-off point of >4.44 was established for IR prediction in this population.

Conclusions

The TyG index is a simple and cost-effective surrogate marker of IR in South American overweight children and adolescents. Moreover, due to its good accessibility, it can be used in large epidemiological studies.
The effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria: findings from a large national cohort
Authors: Joseph Tobin , Ting Joanna , Butler Gary
Published: August 2019

Background

More young people with gender dysphoria (GD) are undergoing hormonal intervention starting with gonadotropin-releasing hormone analogue (GnRHa) treatment. The impact on bone density is not known, with guidelines mentioning that bone mineral density (BMD) should be monitored without suggesting when. This study aimed to examine a cohort of adolescents from a single centre to investigate whether there were any clinically significant changes in BMD and bone mineral apparent density (BMAD) whilst on GnRHa therapy.

Methods

A retrospective review of 70 subjects aged 12–14 years, referred to a national centre for the management of GD (2011–2016) who had yearly dual energy X-ray absorptiometry (DXA) scans. BMAD scores were calculated from available data. Two analyses were performed, a complete longitudinal analysis (n=31) where patients had scans over a 2-year treatment period, and a larger cohort over the first treatment year (n=70) to extend the observation of rapid changes in lumbar spine BMD when puberty is blocked.

Results

At baseline transboys had lower BMD measures than transgirls. Although there was a significant fall in hip and lumbar spine BMD and lumbar spine BMAD Z-scores, there was no significant change in the absolute values of hip or spine BMD or lumbar spine BMAD after 1 year on GnRHa and a lower fall in BMD/BMAD Z-scores in the longitudinal group in the second year.

Conclusions

We suggest that reference ranges may need to be re-defined for this select patient cohort. Long-term BMD recovery studies on sex hormone treatment are needed.
Acquired von Willebrand’s syndrome caused by primary hypothyroidism in a 5-year-old girl
Authors: Flot Claire , Oliver Isabelle , Caron Philippe , Savagner Frédérique , Tauber Maithé , Claeyssens Ségolène , Edouard Thomas
Published: August 2019

Background

Acquired von Willebrand’s syndrome (aVWS) associated with hypothyroidism is rare in children and more often diagnosed during the peripubertal period in the context of Hashimoto’s thyroiditis.

Case presentation

A 5-year-old girl was referred to the paediatric haematology unit for rectal bleeding, anaemia and prolonged activated partial thromboplastin time (aPTT). Her developmental and learning skills were normal. The physical examination revealed severe short stature (height SDS: −3.6) with overweight (body mass index SDS: 1.8) and clinical sign of hypothyroidism. Laboratory investigation revealed aVWS type 1 associated with severe primary hypothyroidism. Anti-thyroid antibodies were negative and thyroid ultrasound found thyroid hypoplasia in favour of congenital hypothyroidism. Restoration of euthyroidism was associated with increased growth velocity and normalisation of coagulation parameters.

Conclusion

This report highlights the importance of excluding an underlying pathology (including hypothyroidism) in children with suspected VWS, even in young age.
A novel DCAF17 homozygous mutation in a girl with Woodhouse-Sakati syndrome and review of the current literature
Authors: Kurnaz Erdal , Türkyılmaz Ayberk , Yaralı Oğuzhan , Demir Berrin , Çayır Atilla
Published: August 2019

Background

Woodhouse-Sakati syndrome (WSS) (OMIM#241080) is an extremely rare multisystemic disease. Alopecia, hypogonadism, loss of hearing, hypothyroidism, diabetes mellitus (DM) and neurological disorders are the components of this syndrome. The syndrome is caused by homozygous or compound heterozygous mutations in DCAF17, and has recently been implicated in the development of both male and female gonads, thus resulting in hypogonadism.

Case report

A 16-year-old girl with consanguineous parents was admitted to our hospital with absence of breast development and amenorrhea. Hypogonadism was detected, in the form of hypergonadotropic hypogonadism. Whole-exome sequencing was used to identify the genetic etiology underlying the hypogonadism. A novel homozygous variant c.1091 + 1G > A was detected in DCAF17. Both parents were sequenced and identified as heterozygous for the same mutation.

Conclusions

We report a novel mutation detected in the DCAF17 gene and discuss the clinical findings in patients with previously reported mutations. Various manifestations of WSS, such as alopecia, endocrinological and neurological disorders, do not emerge until later in life, and therefore this situation can be challenging to diagnose particularly in pediatric cases, as in the present report. Careful attention should be paid to these additional findings, which may lead to early diagnosis and reduced genetic analysis costs, in patients with hypogonadism. In addition, there was no obvious genetic-phenotype correlation in reported cases.
Ghrelin and leptin levels in children with anxiety disorders
Authors: Ozmen Sevgi , Şeker Asilay , Demirci Esra
Published: August 2019

Background

Anxiety disorders are common psychiatric disorders in childhood and an important health problem that is associated with the risk of serious mental, educational and economical problems. Researchers have mentioned many different mechanisms in the etiopathology of anxiety disorders. This study aimed to investigate ghrelin and leptin levels in children with anxiety disorders and thus to contribute to the clarification of anxiety in children.

Methods

Forty-three children aged 6–12 years with a diagnosis of the Anxiety Disorder according to DSM 5 and 21 healthy children age- and gender-matched to the study group were included. All the subjects were assessed with Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and State-Trait Anxiety Inventory for Children (STAI-C) scale. Blood samples were obtained in the morning and serum ghrelin and leptin levels were measured with enzyme-linked immunosorbent assay (ELISA) kits.

Results

In the anxiety group the ghrelin levels were higher than the control group (p = 0.037) but there was no significant difference between the leptin levels (p = 0.430). Also, when the girls in the anxiety group and the girls in the control group were compared, ghrelin levels were higher in the anxiety group (p < 0.01).

Conclusions

These findings suggest that ghrelin may play a significant role in the etiologic mechanisms of anxiety disorders. However, more detailed studies are needed to explain the linkage between anxiety disorders and neuropeptides.
Infantile cerebral infarction caused by severe diabetic ketoacidosis in new-onset type 1 diabetes mellitus
Authors: Suzuki Junichi , Fuchigami Tatsuo , Kawamura Kengo , Aoki Masako , Urakami Tatsuhiko , Morioka Ichiro
Published: August 2019

Background

Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). Infants and children with new-onset T1DM may present with DKA, and the risk of cerebral edema is high in infantile DKA.

What is new?

Neurological deterioration during an episode of DKA is usually attributed to cerebral edema and cerebrovascular accidents. However, cerebral infarction is a very rare complication in infantile DKA.

Case presentation

We describe a rare case of infantile cerebral infarction caused by severe DKA in a patient with new-onset T1DM.

Conclusions

Cerebral infarction is an important intracranial complication in infantile DKA. Careful observation and treatment for DKA during the first 24 h of therapy are necessary in infants with new-onset T1DM because the risk of cerebral infarction is highest during this timeframe.
The Potential of Magnetic Nanoparticles for Diagnosis and Treatment of Cancer Based on Body Magnetic Field and Organ-on-the-Chip
Authors: Alirezaie Alavijeh Ali , Barati Mohammad , Barati Meisam , Abbasi Dehkordi Hussein
Published: August 2019

Cancer is an abnormal cell growth which tends to proliferate in an uncontrolled way and, in some cases, leads to metastasis. If cancer is left untreated, it can immediately cause death. The use of magnetic nanoparticles (MNPs) as a drug delivery system will enable drugs to target tissues and cell types precisely. This study describes usual strategies and consideration for the synthesis of MNPs and incorporates payload drug on MNPs. They have advantages such as visual targeting and delivering which will be discussed in this review. In addition, we considered body magnetic field to make drug delivery process more effective and safer by the application of MNPs and tumor-on-chip.
Preparation, Physicochemical Characterization and Oxidative Stability of Omega-3 Fish Oil/α-Tocopherol-co-Loaded Nanostructured Lipidic Carriers
Authors: Shahparast Yaser , Eskandani Masoud , Rajaei Ahmad , Yari Khosroushahi Ahmad
Published: August 2019

Purpose: This study aimed to improve the pharmacokinetic behavior of polyunsaturated fatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxic hydroperoxides, develops off-flavors and shortens shelf-life. Methods: Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherol was successfully prepared by melt blending and hot sonication method to enhance the oxidative stability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stability of prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) and thiobarbituric acid (TBA) during 40 days. Results: Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longterm stability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days of storage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed better oxidative stability compared with the all other formulations. Also, it was found that the NLC as an encapsulation method was more successful to inhibit the formation of the primary oxidation products than the secondary oxidation products. Conclusion: Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherol within the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clear beverages.
Anti-tumor Effect of Quercetin Loaded Chitosan Nanoparticles on Induced Colon Cancer in Wistar Rats
Authors: Rashedi Jalil , Ghorbani Haghjo Amir , Mesgari Abbasi Mehran , Dastranj Tabrizi Ali , Yaqoubi Shadi , Sanajou Davoud , Ashrafi Jigheh Zahra , Namvaran Ali , Mohammadi Ali , Mohammadi Khoshraj Jalal , Baradaran Behzad
Published: August 2019

Purpose: This study was aimed to evaluate the site-specific drug delivery of 5-FU with chitosan (CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. Methods: Cross-linked CS-Qu nanoparticles (NPs) were prepared by ionotropic gelation method. Physicochemical characterization of NPs was performed by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency (LE). 1, 2-Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induce adenocarcinoma tumors on inbred male Wistar rats’ colon. The treatment group of rats was administered through enema with NPs dispersion. Hematoxylin and eosin staining were performed to the histopathological examination of tumors. Results: Zeta potential and particle size for NPs were +53.5 ± 5 mV and 179 ± 28 nm, respectively. About 96% Qu LE was obtained with a maximum release of 5.63 ±1.59% and 4.62 ± 1.33% after 24 hours in PB solution with pH values of 6 and 7.4, respectively. The numbers of 8 to 21 tumors were observed in all rats administered with DMH and DSS. Significantly decreasing of microvascular density and mitosis count was detected in the treatment group in comparison with cancerous group (P = 0.032 for the former compared to P = 0.016 for the later), respectively. Furthermore, the treatment group showed a high apoptosis rate (P = 0.038). Conclusion: The developed Qu-loaded CS NPs were good candidates for site-specific and sustained drug release in enema treatment. Decreasing of microvascular density and mitosis count, along with increasing the apoptosis percent in the treatment group proved that the NPs could have promising results in site-specific and sustained drug delivery against colorectal cancer.
Characterization and Stability of the Antimony-Quercetin Complex
Authors: Barbosa Valcilaine Teixeira , de Menezes Janaína Barros , Santos Josué Carinhanha Caldas , Bastos Maria Lysete de Assis , Araújo-Júnior João Xavier de , Nascimento Ticiano Gomes do , Basílio-Júnior Irinaldo Diniz , Grillo Luciano Aparecido Meireles , Dornelas Camila Braga
Published: August 2019

Purpose: Quercetin is a flavonoid known for its therapeutic properties and for forming complexes. Although the antimony-quercetin (SbQ) complex has been produced before, no previous exploration of its characteristics has been published in literature. Thus, this study aimed to characterize this complex, assess its stability and investigate its complexation site through its antibacterial activity. Methods: The SbQ complex was synthetized using Sb(III) potassium tartrate trihydrate and quercetin anhydrous (1:1) (v/v) as a solution and dried using three methods: rotaevaporation, lyophilization and spray drying. The material, in solution, was analyzed by UV-vis and fluorimetry; and, in the powder, by X-ray diffraction (XRD), both scanning electronic and fluorescence microscopy and infrared spectroscopy (FT-IR). Antimicrobial activity was evaluated via broth microdilution. Results: UV-vis exhibited a shoulder peak at 291 nm indicating metal chelation at C-ring of quercetin and confirmed 1:1 stoichiometry. Spectrofluorimetry showed an increase of intensity with the complex formation with an emission band (525 nm). After drying, XRD and SEM indicated loss of crystallinity and a difference in shape and size of the complex compared to its precursors. FT-IR suggested by a shift of frequency of the carbonyl group (1661 cm-1) that the quercetin bond to antimony by the C-3, followed by positions C-5 and C-4 carbonyl, which has been confirmed by MIC through the structure-activity relationship of the antibacterial activity of quercetin. Conclusion: These results provided a characterization of SbQ complex with the confirmation of its binding site, working as a guide for future studies involving this complex.
Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine
Authors: Mohammadian Mahshid , Zeynali-Moghaddam Shima , Khadem Ansari Mohammad Hassan , Rasmi Yousef , Fathi Azarbayjani Anahita , Kheradmand Fatemeh
Published: August 2019

Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.
Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation
Authors: Meiyanto Edy , Putri Herwandhani , Arum Larasati Yonika , Yudi Utomo Rohmad , Istighfari Jenie Riris , Ikawati Muthi , Lestari Beni , Yoneda-Kato Noriko , Nakamae Ikuko , Kawaichi Masashi , Kato Jun-Ya
Published: August 2019

Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative agent. Methods: Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosis incidence, and ROS intracellular level were determined by flow cytometry. Cell senescence was observed under senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expression of matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA, while other proteins expression were detected using immunoblotting. Results: Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellular ROS level. We also revealed that PGV-1 bound to several ROS-metabolizing enzymes, including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), N-ribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldo-keto reductase family 1 member c1 (AKR1C1). As an antimetastatic agent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependent manner suggesting it still potent to inhibit metastatic cells. Conclusion: Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferative and anti-metastatic agent.
Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression
Authors: Satari Atefeh , Amini Sayed Asadollah , Raeisi Elham , Lemoigne Yves , Heidarian Esfandiar
Published: August 2019

Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.
Evaluation of the Cytotoxic and Apoptogenic Effects of Glabridin and Its Effect on Cytotoxicity and Apoptosis Induced by Doxorubicin Toward Cancerous Cells
Authors: Modarresi Masoud , Hajialyani Marziyeh , Moasefi Narges , Ahmadi Farahnaz , Hosseinzadeh Leila
Published: August 2019

Purposes: In the present study, we tried for the first time to examine the anti-proliferative and anti-apoptogenic effect of Glabridin (Glab) toward three groups of cancer cells (SKNMC, H1299, and A2780). Furthermore, the possibility of co-administration of Glab with doxorubicin (DOX) to these cells was also examined to find out whether Glab can potentiate the cytotoxic effect of this chemotherapy agent. Methods: Different cellular assays (MTT, caspase-3 activity, MMP, RT-PCR analysis) were carried out on the cancer cells treated with Glab. Results: Cellular toxicity assay revealed that Glab can potentially reduce the viability of these cells with IC50 concentrations up to 10, 12, and 38 μM toward A2780, SKNMC, and H1299 cell lines, respectively. The results of MMP and caspase-3 activity assays, in association with the results corresponding to the BAX and Bcl-2 gene expressions, altogether revealed that Glab can exert apoptogenic effect on these cells. The intrinsic mitochondrial pathway was found to be the main mechanism, in which Glab induced apoptosis toward H1299 cells and SKNMC cells, while the apoptosis mechanism for A2780 cells could be probably through extrinsic pathway. Glab also potentiated the cytotoxic effect of DOX and its accumulation in H1299 cell line. Conclusion: The results of this study revealed the promising cytotoxic role of Glab on different carcinoma cells. These data also suggested that co-chemotherapy method using Glab could be effective for treatment of cancer, but further in-vivo and clinical studies are still needed to assure these results.