bluuebunny/crossref_metadata_2025 huggingface dataset:
Reasons for mortality in elderly and senile patients with hip osteoporotic fractures
Authors: Averkieva Yu. V. , Raskina T. A. , Grigorieva I. I. , Letaeva M. V. , Malyshenko O. S.
Published: January 2020

Aim. To identify the causes of mortality in elderly and senile patients with non-traumatic hip fracture during the first year after fracture.

Materials and Methods. The reasons for death were analyzed in the cohort consisted of 432 patients with a non-traumatic hip fracture: 328 women aged from 70 to 82 years (mean age 75.4) and 104 men aged from 60 to 80 years (mean age 71.5).

Results. It was revealed that in first 6 months after the injury, death occurred in 22.00 % of cases (95 from 432 patients died). After 12 months period, mortality increased to 137 cases (total mortality accounted for 31.80 %). Most of the deaths were due to cardiovascular system diseases. Cardiovascular causes were in 93 cases (21.00 %), without any gender difference: 22 in men (21.10 %) and 71 in women 21.60 %). The ratio of cardiovascular diseases in the total number of fatal outcomes was 93 (67.80 %), comparable for men and women subgroups (66.00 and 68.30 % respectively; p = 0.65). Diseases of respiratory system as a reason for death accounted for 16.80 % in the structure of total mortality: 15.10 % in men subgroup and 17.30 % in women (p = 0.31). Mortality from tumors was defined in 10.90 % from all cases of death: in men 9.09 % cases and in women 11.50 % cases (p = 0.45). The ratio of digestive system disorders as the cause of death accounted for 3.60 %: 6.06 % in men and 2.90 % in women respectively (p = 0.1).

Conclusions. Cardiovascular and respiratory diseases were the most common causes of first-year mortality in elderly and senile patients with non-traumatic hip fracture. The gender differences in mortality rates were not found.
Early determination of bacteriological status of biological fluid samples as effective method of diagnosing infectious complications in patients of transplant clinic
Authors: Miloserdov I. A. , Drabkina I. V. , Saydulaev D. A. , Kurbangulov I. R. , Sharapchenko S. O. , Kormilitsina V. G. , Safonova T. B. , Petrukhina M. I. , Gabrielyan N. I.
Published: January 2020

The concept of quality assurance in the health care system is popular for medical institutions all over the world. The problem of global multidrug resistance of pathogenic and opportunistic flora causes an urgent need for new approaches and methods of renal failure (particularly bacteriuria) rapid diagnosis.

Objectives. Evaluate the benefits of laser light-scattering method in early diagnosis of renal failure and infectious complications after kidney transplantation.

Methods. 220 urine samples from 129 patients were examined. Each sample was evaluated by traditional method and an automated laser light-scattering system simultaneously.

Results. The automated method allowed to get the result in an average of 2 hours and give a result of bacteriuria availability with indicating the class of the pathogen by Gram. Discrepancy between the results of classical and automated methods was observed in 6.8 % of all samples, which is the standard for similar clinical trials.

Conclusions. Laser light-scattering method has clear advantages over traditional methods. Diagnosis of urinary tract infections in kidney recipients in a shorter time (3.5 hours) is especially important. The economic benefit of automated process allows to reduce the costs of the hospital for bacteriological studies by 1.5 times.
Results of dispensary observation of tuberculosis patients in Russian Federation
Authors: Shilova M. V.
Published: January 2020

Dispensary observation of patients with tuberculosis is the basis for the provision of TB care to the population. The data on the number of TB facilities and TB specialists from 20091 to 2018 are presented. A decrease in the incidence rate over the past 27 years is shown from 1991 to 2018 of the number of all patients under clinical supervision, including patients with tuberculosis. The data on the organization and results of the follow-up of patients with tuberculosis are presented: indicators of clinical cure and mortality, as well as the reliability of some indicators. The factors affecting the results of the follow-up of patients with tuberculosis, the presence of resistance of the office to anti-TB drugs and HIV-infection are examined.
Comprehensive study of number and types of saturated and polyunsaturated fatty acids in composition of preparations
Authors: Gromova O. A. , Torshin I. Yu. , Zaychik B. Ts. , Ruzhitsky A. O.
Published: January 2020

When prescribing a vitamin‑mineral complex or a drug containing docosahexaenoic acid (DHA) to a pregnant, lactating mother and child, it is expected to receive the effect from the subsidy of this polyunsaturated fatty acid (omega‑3 PUFA). In the case when the preparation contains additional impurities, the magnitude and nature of the effect may differ from the expected ones. In this work, we conducted a comprehensive study of the composition of 11 omega‑3 PUFA preparations with chromatographic determination of more than 40 metabolites of fatty acids and other compounds. The obtained data on the composition of the extracts were analyzed using modern methods of intellectual analysis. As a result, quantitative markers were obtained that made it possible to separate preparations based on standardized omega‑3 PUFAs from less standardized ones based on chromatographic analysis of the fatty acid composition of the preparations: marker ‘EPA + DHA’, marker ‘ω6 + ω11’ and standardization coefficient evaluating the conformity of measured levels of omega‑3 PUFAs to manufacturer declared. Based on the data obtained, highly standardized (Elevit Feeding, Omacor), medium and low standardized preparations were selected. It is recommended to take these data into account when prescribing and choosing vitamin complexes for nursing women, preferring highly standardized ones.
Correlation of body weight at birth with risk of cardiovascular disease and possibility of cardiovascular prophylaxis
Authors: Khurasev A. B. , Kuznetsova I. V.
Published: January 2020

The results of a retrospective analysis and a one‑stage study conducted among 352 teenage girls and 952 postmenopausal women demonstrate that pathology of the cardiovascular system (CVS) can be programmed in the antenatal period. Mass and growth indicators of the newborn are an important morphofunctional characteristic of a person and can be used not only to assess physical development throughout life, but also as a marker of risk of one or another somatic pathology. Timely identification of risk factors for adolescent health disorders and their adequate correction can significantly improve the results of cardiovascular prophylaxis. Equally important is the prevention of insufficient or excessive weight gain during fetal development, which can be achieved by prescribing vitamin‑mineral complexes to pregnant women.
Method of calculating volume of bone-substituting material during sinus-lifting operation using digital technologies
Authors: Kutsenko A. P. , Dolgalev A. A. , Zelensky V. A. , Aleshin D. S. , Gladyshev M. V. , Put V. A. , Lezhava N. L.
Published: January 2020

The method of digital planning of sinus-lifting operation using the data of computed tomography, laser surface scanning of dentition, as well as a number of computer programs, the use of which in the treatment of tooth loss allows you to accurately determine the volume of bone-substituting material and the area of implant placement. This technique is based on the digital calculation of the volume of bone-substituting material required for introduction into the maxillary sinus during sinus-lifting operation.
LC‑spectra analysis algorithm for non‑invasive diagnostics by oropharyngeal washout samples
Authors: Nikolaev A. I. , Antonova I. N. , Donskaya O. S. , Vladimirova L. G.
Published: January 2020

The purpose of the study was to offer an alternative algorithm for analysis of LC‑spectra for non‑invasive diagnosis of oropharyngeal samples flushing.

Materials and methods. The study included 23 patients with gallstone disease, 22 patients with urolithiasis, 22 patients with salivary stone disease, 4 patients with abundant dental sediments and 13 persons in the control group. Materials for research were serum and oropharyngeal washout. Research conducted by laser correlation spectroscopy in laser spectroscopy correlation computerized LCS‑03‑”INTOX”.

The results. In the study of systems with unbalanced anisotropic nanoparticles should be no stray light to the square of the particle and its linear size indicators each channel light scattering, spectrum is divided into the radius of the particles corresponding to this channel and in future all newly obtained spectrum is converted to 1. To reduce the dimensionality of the data analysis was carried out of the whole array of spectra of SC and LC–CSG principal component method (CC) with varimax ro‑ tation (et). In both types of spectrum first 12 GK explained more than 96 % of the variance, the remaining 4 % were accepted as the noise component. Top values on the basis of values of factor loadings CC has compiled a algorithm to convert primary 32‑channel spectra LKS in 12‑band by calculating light scattering totals in each range and their normalization relative to the total on all of the flare 12 fixed ranges, received for the 1 (100 %) with the help of several successive stages of the LST with step by step inclusion of variables applied to spectra LKS SC and CSG patients with biomineralopathy can be fairly effective discrimination against diseases as from healthy individuals, and among themselves.

Conclusion. The algorithm processing LC‑spectra of SC and CSG, including rationing by the number of particles of light scattering spectra, the reducer dimension range from 32 to 12 and consistent classification of diseases by methods of linear discriminant analysis. Developed classification rules allow to diagnose diseases on the newly obtained samples of blood serum and/or CSG. Since the LST and GCF serum gives similar results to the classification based on ‘Disease’, for diagnostic purposes you can do only the CSG analysis without blood sampling, however, the LST for the serum and the CSG allows you to increase the power classification on the basis of ‘Disease’ compared to the analysis of these same data separately.
Clinical and biochemical predictors of neurological disorders
Authors: Serikova I. Yu. , Shumacher G. I. , Vorobyova E. N. , Batanina I. A. , Vorobyov R. I.
Published: January 2020

The aim of this study is to identify clinical and biochemical predictors of neurological disorders in adolescents who have suffered mild perinatal damage of the central nervous system. We examined 120 adolescents (62 girls and 58 boys) aged 13–16 years, who were hospitalized in the city Children’s Neurological Department. It was found that adolescents with perinatal lesions of the central nervous system, activated lipid peroxidation processes and revealed an increase in the concentration of protein S 100, which in the future could lead to the development of neurodegeneration processes. In addition, a positive correlation between the lipid peroxidation processes nd the concentration of the nerve tissue damage marker was revealed. The results indicate that the level of neurospecific protein — protein S 100, parameters of the oxidant‑antioxidant system, perinatal factors can be used as predictors of chronic nervous tissue processes.
Functional and metabolic disorders in patients with cholelithiasis after undergone cholecystectomy
Authors: Tikhonov S. V. , Dekkanova V. D. , Bakulina N. V. , Korzheva M. D. , Kalinina M. A.
Published: January 2020

The article describes the results of a clinical observational study of patients with cholelithiasis after cholecystectomy. The article is about the metabolic disorders in patients with gallstone disease, the mechanisms of development of functional and metabolic disorders after cholecystectomy. Particular attention is paid to the genetic, hormonal mechanisms, the role of microbiota and bile acids.
Method of bioimpendancemetria for assessing metabolism in colorectal cancer and pancreatic cancer
Authors: Kostyuchenko L. N. , Kruglov A. D. , Kostyuchenko M. V. , Lychkova A. E.
Published: January 2020

The method of bioimpedance measurement allows to evaluate the use of a complex of surgical and chemotherapeutic methods accompanied by nutritional support. Patients with colorectal cancer need different saturation of postoperative nutritional support in 90 % of cases, as well as dynamic operational control of the corrected nutritional status. Vector analysis of bioimpedansograms provides qualitative indicators of soft tissue changes that do not depend on body size (information on hydration, exicosis, body cell mass and cell integrity). The study of body composition by bioimpedance method allows to reveal latent sarcopenia and to choose personalized nutritional correction programs that take into account the dynamics of metabolic disorders at the cell level.
Evolution of approaches in treatment of acute pain syndrome (review)
Authors: Vetsheva M. S. , Podkorytova O. L. , Churakov V. O. , Dushkin A. D. , Golovashchenko M. P.
Published: January 2020

In recent years, the treatment of acute pain syndrome has been considered as an independent direction in anesthesiology and intensive care. New schemes of postoperative analgesia and new drugs developed by pharmacologists are actively being introduced. One of the newer regimens for pain relief is patient-controlled analgesia (CPA) or on-demand analgesia. The development of the concept of fast track surgery, one of the most widely discussed areas for the development of innovative technologies in modern surgery, from the point of view of the anesthesiologist of the resuscitation specialist, minimizes the stress response of the body to surgical aggression at all stages of the perioperative period. Increasingly, the method of preemptive analgesia is used more widely, based on the use of analgesics before the start of the operation, which helps to prevent the occurrence of peripheral and central sensitization.
MULTIMEDIA INTERAKTIF BERBASIS STEM PADA KONSEP PENCEMARAN LINGKUNGAN UNTUK MENINGKATKAN KEMAMPUAN BERPIKIR KRITIS SISWA
Authors: Pramuji Lili , Permanasari Anna , Ardianto Didit
Published: January 2020

Penelitian ini bertujuan untuk menghasilkan multimedia interaktif berbasis STEM yang dapat meningkatkan kemampuan berpikir kritis siswa pada konsep pencemaran lingkungan. Metode penelitian yang digunakan adalah metode pengembangan atau Research and Development (R&D) dengan desain ADDIE (Analysis, Design, Development, Implementation, Evaluation). Instrumen yang digunakan dalam penelitian ini terdiri dari lembar validasi ahli dan guru,  soal tes kemampuan berpikir kritis, lembar angket siswa untuk mengetahui tanggapan siswa terhadap multimedia interaktif. Untuk mengetahui efektifitas multimedia interaktif terhadap peningkatan kemamapuan berpikir kritis dilakukan tes pilihan ganda beralasan. Hasil penelitian menunjukkan bahwa 1) hasil validasi ahli diperoleh nilai rata-rata 3,1 (baik) dan hasil validasi 3 orang guru diperoleh nilai rata-rata 3,5 (sangat baik), 2) multimedia interaktif dapat meningkatkan kemampuan berpikir kritis siswa yang ditunjukkan dengan rata-rata hasil pretes sebesar 9.64%, rata-rata postes sebesar 54,82% dan rata-rata %N-Gain sebesar 49,90% (sedang), 3) tanggapan siswa terhadap penggunaan multimedia interaktif dalam pembelajaran memperoleh nilai 88,46% (sangat baik). Kata Kunci: Multimedia Interaktif, STEM, Kemampuan Berpikir Kritis
PENGEMBANGAN BAHAN AJAR BERBASIS PROYEK PADA MATERI ENERGI UNTUK MENINGKATKAN LITERASI SAINS SISWA
Authors: Hardjo Fanny Nadia , Permanasari Anna , Permana Irvan
Published: January 2020

Penelitian ini bertujuan untuk menghasilkan modul pembelajaran berbasis proyek yang dapat meningkatkan literasi sains siswa pada materi energi. Metode penelitian yang digunakan dalam penelitian ini adalah metode pengembangan atau Research and Development (R&D) dengan desain ADDIE (Analysis, Design, Development, Implementation, Evaluation). Instrumen yang digunakan dalam penelitian ini terdiri dari lembar validasi ahli yang digunakan untuk memvalidasi bahan ajar oleh ahli dan guru IPA (5 ahli), soal keterbacaan bahan ajar (100 partisipan siswa), lembar angket untuk mengetahui respon siswa dan guru terhadap bahan ajar. Untuk mengetahui dampak bahan ajar terhadap literasi sains siswa dilakukan tes pilihan ganda berbasis literasi sains. Hasil penelitian menunjukkan bahwa 1) pembuatan modul melalui beberapa tahap yaitu analisis kebutuhan, desain dan pengembangan, implementasi, evaluasi 2) hasil validasi pada komponen kelayakan isi, kelayakan penyajian dan kelayakan bahasa rata-ratanya 88% (sangat baik) dan hasil validasi oleh 2 guru IPA  memperoleh nilai rata-rata 95% (sangat baik) 3) bahan ajar berbasis proyek dapat meningkatkan minat siswa dibuktikan dengan hasil tanggapan siswa memperoleh nilai 90% (sangat baik) dan dapat memudahkan guru dalam pembelajaran dibuktikan dengan rata-rata tanggapan guru 86% (sangat baik) 4) pengembangan bahan ajar berbasis proyek pada materi energi dapat meningkatkan literasi sains siswa pada materi energi ditunjukan dengan hasil pretest sebesar 54, rata-rata posttest sebesar 69 dan N-gain 0,43 (sedang). Kata Kunci: Bahan Ajar, Modul Project Based Learning, Literasi Sains
PENGEMBANGAN PEMBELAJARAN PADA MATERI TEKANAN ZAT UNTUK KETERAMPILAN BERPIKIR KRITIS DAN PENGUASAAN KONSEP SISWA SMP
Authors: Kania Dewi , Rubini Bibin , Ardianto Didit
Published: January 2020

Keterampilan berpikir siswa, baik berpikir kritis maupun penguasaan konsep merupakan keterampilan yang penting untuk dimiliki agar dapat memecahkan persoalan-persoalan yang dihadapi dalam dunia yang senantiasa berubah. Pembelajaran IPA dengan pendekatan Kontekstual merupakan suatu alternatif pendekatan yang berupaya meningkatkan keterampilan berpikir kritis dan penguasaan konsep siswa agar terus terlatih dengan baik. Penelitian ini bertujuan untuk menelaah peningkatan keterampilan berpikir kritis dan penguasaan konsep antara siswa yang memperoleh pembelajaran IPA dengan pendekatan Kontekstual dan siswa yang memperoleh pembelajaran dengan pembelajaran konvensional baik ditinjau secara keseluruhan maupun ditinjau secara kelompok siswa (kelompok atas dan kelompok bawah). Selain itu diungkap pula sikap siswa terhadap pembelajaran IPA dengan pendekatan Kontekstual  Desain penelitian ini adalah pre-test post-test control group design. Penelitian ini dilakukan di SMP pada kelas VIII. Data penelitian dikumpulkan melalui tes . Analisis data dilakukan terhadap rerata gain ternormalisasi antara kedua kelompok sampel dengan menggunakan kesamaan dua rerata. Hasil penelitian menunjukkan bahwa peningkatan keterampilan berpikir kritis dan penguasaan konsep siswa yang belajar dengan pendekatan Kontekstual lebih baik secara signifikan daripada siswa yang belajar dengan pembelajaran konvensional,.. Selanjutnya analisis data angket sikap siswa memperlihatkan bahwa siswa menunjukan sikap positif terhadap pembelajaran IPA  dengan pendekatan Kontekstual. Kata Kunci: Keterampilan berpikir kritis dan Penguasaan konsep, pendekatan Kontekstual
Opinions towards Companion Animals and Their Welfare: A Survey of Croatian Veterinary Students
Authors: Mikuš Tomislav , Ostović Mario , Sabolek Ivana , Matković Kristina , Pavičić Željko , Mikuš Ornella , Mesić Željka
Published: January 2020

This survey was the first one investigating opinions of veterinary students in Croatia towards companion animals and their welfare, with special reference to dogs and cats as the most popular companion animals in the European Union. The study included students of all six years of the integrated undergraduate and graduate veterinary medicine study programme in Croatia. First-year students were surveyed twice, before and after having attended the course on animal welfare. Student opinions were assessed on the basis of their mean responses to five-point Likert scale questions and frequency of responses to Yes/No/I do not know questions and ratio scale questions. Study results revealed students to have strongly positive opinions towards companion animals and their welfare. The majority of student statements did not differ significantly between the first and sixth study years or before and after having attended the animal welfare course in the first study year, mostly yielding a straight, non-fluctuating line. Students were not sure whether welfare of companion dogs and cats was compromised. Study results pointed to reliable and reasonable opinions of veterinary medicine students in Croatia towards companion animals and their welfare, as well as to the welfare issues these species may be facing nowadays.
FAK Structure and Regulation by Membrane Interactions and Force in Focal Adhesions
Authors: Tapial Martínez Paula , López Navajas Pilar , Lietha Daniel
Published: January 2020

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase with key roles in the regulation of cell adhesion migration, proliferation and survival. In cancer FAK is a major driver of invasion and metastasis and its upregulation is associated with poor patient prognosis. FAK is autoinhibited in the cytosol, but activated upon localisation into a protein complex, known as focal adhesion complex. This complex forms upon cell adhesion to the extracellular matrix (ECM) at the cytoplasmic side of the plasma membrane at sites of ECM attachment. FAK is anchored to the complex via multiple sites, including direct interactions with specific membrane lipids and connector proteins that attach focal adhesions to the actin cytoskeleton. In migrating cells, the contraction of actomyosin stress fibres attached to the focal adhesion complex apply a force to the complex, which is likely transmitted to the FAK protein, causing stretching of the FAK molecule. In this review we discuss the current knowledge of the FAK structure and how specific structural features are involved in the regulation of FAK signalling. We focus on two major regulatory mechanisms known to contribute to FAK activation, namely interactions with membrane lipids and stretching forces applied to FAK, and discuss how they might induce structural changes that facilitate FAK activation.
2-deoxy-d-glucose Ameliorates Animal Models of Dermatitis
Authors: Choi Soo Young , Heo Min-Jeong , Lee Chanmi , Choi Yeong Min , An In-sook , Bae Seunghee , An Sungkwan , Jung Jin Hyuk
Published: January 2020

Glucose metabolism is a key metabolic pathway that orchestrates cellular homeostasis by generating ATP, nucleotides, and amino acids. Abnormal glucose signaling has been found in many diseases including cancers and inflammatory diseases. According to recent report, glycolysis contributes to pathogenesis of psoriasis and ablation of Glut1 attenuates animal models of psoriasis. While we were screening a molecular target for atopic dermatitis, we found the levels of glucose transporters including Glut1 (SLC2a1) and Glut3 (SLC2a3) are highly expressed in skin biopsies of dermatitis patients from multiple datasets. We demonstrated that administration of 2-deoxy-d-glucose (2DG) ameliorates animal models of 12-o-tetradecanoylphorbol-13-acetate (TPA) and oxazolone induced dermatitis using morphological and histological analysis. These results suggest that inhibition of glucose metabolism ameliorates dermatitis in animal models.
Cerebellar Transcranial Magnetic Stimulation Reduces the Silent Period on Hand Muscle Electromyography During Force Control
Authors: Matsugi Akiyoshi , Douchi Shinya , Suzuki Kodai , Oku Kosuke , Mori Nobuhiko , Tanaka Hiroaki , Nishishita Satoru , Bando Kyota , Kikuchi Yutaka , Okada Yohei
Published: January 2020

This study aimed to investigate whether cerebellar transcranial magnetic stimulation (C-TMS) affected the cortical silent period (cSP) induced by TMS over the primary motor cortex (M1) and the effect of interstimulus interval (ISI) on cerebellar conditioning and TMS to the left M1 (M1-TMS). Fourteen healthy adult participants were instructed to control the abduction force of the right index finger to 20% of the maximum voluntary contraction. M1-TMS was delivered during this to induce cSP on electromyograph of the right first dorsal interosseous muscle. TMS over the right cerebellum (C-TMS) was conducted prior to M1-TMS. In the first experiment, M1-TMS intensity was set to 1 or 1.3 × resting motor threshold (rMT) with 20-ms ISI. In the second experiment, the intensity was set to 1 × rMT with ISI of 0, 10, 20, 30, 40, 50, 60, 70, or 80 ms, and no-C-TMS trials were inserted. In results, cSP was significantly shorter in 1 × rMT condition than in 1.3 × rMT by C-TMS, and cSP was significantly shorter for ISI of 20–40 ms than for the no-C-TMS condition. Further, motor evoked potential for ISI40-60 ms were significantly reduced than that for ISI0. Thus, C-TMS may reduce cSP induced by M1-TMS with ISI of 20–40 ms.
Phenethyl Isothiocyanate Suppresses Stemness in the Chemo- and Radio-Resistant Triple-Negative Breast Cancer Cell Line MDA-MB-231/IR Via Downregulation of Metadherin
Authors: Nguyen Yen Thi-Kim , Moon Jeong Yong , Ediriweera Meran Keshawa , Cho Somi Kim
Published: January 2020

Resistance to chemotherapy and radiation therapy is considered a major therapeutic barrier in breast cancer. Cancer stem cells (CSCs) play a prominent role in chemo and radiotherapy resistance. The established chemo and radio-resistant triple-negative breast cancer (TNBC) cell line MDA-MB-231/IR displays greater CSC characteristics than the parental MDA-MB-231 cells. Escalating evidence demonstrates that metadherin (MTDH) is associated with a number of cancer signaling pathways as well as breast cancer therapy resistance, making it an attractive therapeutic target. Kaplan–Meier plot analysis revealed a correlation between higher levels of MTDH and shorter lifetimes in breast cancer and TNBC patients. Moreover, there was a positive correlation between the MTDH and CD44 expression levels in The Cancer Genome Atlas breast cancer database. We demonstrate that MTDH plays a pivotal role in the regulation of stemness in MDA-MB-231/IR cells. Knockdown of MTDH in MDA-MB-231/IR cells resulted in a reduction in the CSC population, aldehyde dehydrogenase activity, and major CSC markers, including β-catenin, CD44+, and Slug. In addition, MTDH knockdown increased reactive oxygen species (ROS) levels in MDA-MB-231/IR cells. We found that phenethyl isothiocyanate (PEITC), a well-known pro-oxidant phytochemical, suppressed stemness in MDA-MB-231/IR cells through ROS modulation via the downregulation of MTDH. Co-treatment of PEITC and N-Acetylcysteine (a ROS scavenger) caused alterations in PEITC induced cell death and CSC markers. Moreover, PEITC regulated MTDH expression at the post-transcriptional level, which was confirmed using cycloheximide, a protein synthesis inhibitor.
Mutation Enrichment and Transcriptomic Activation Signatures of 419 Molecular Pathways in Cancer
Authors: Zolotovskaia Marianna A. , Tkachev Victor S. , Seryakov Alexander P. , Kuzmin Denis V. , Kamashev Dmitry E. , Sorokin Maxim I. , Roumiantsev Sergey A. , Buzdin Anton A.
Published: January 2020

Carcinogenesis is linked with massive changes in regulation of gene networks. We used high throughput mutation and gene expression data to interrogate involvement of 278 signaling, 72 metabolic, 48 DNA repair and 47 cytoskeleton molecular pathways in cancer. Totally, we analyzed 4910 primary tumor samples with individual cancer RNA sequencing and whole exome sequencing profiles including ~1.3 million DNA mutations and representing thirteen cancer types. Gene expression in cancers was compared with the corresponding 655 normal tissue profiles. For the first time, we calculated mutation enrichment values and activation levels for these pathways. We found that pathway activation profiles were largely congruent among the different cancer types. However, we observed no correlation between mutation enrichment and expression changes both at the gene and at the pathway levels. Overall, positive median cancer-specific activation levels were seen in the DNA repair, versus similar slightly negative values in the other types of pathways. The DNA repair pathways also demonstrated the highest values of mutation enrichment. However, the signaling and cytoskeleton pathways had the biggest proportions of representatives among the outstandingly frequently mutated genes thus suggesting their initiator roles in carcinogenesis and the auxiliary/supporting roles for the other groups of molecular pathways.
Metabolism of Estrogens: Turnover Differs between Platinum-Sensitive and -Resistant High-Grade Serous Ovarian Cancer Cells
Authors: Poschner Stefan , Wackerlig Judith , Castillo-Tong Dan Cacsire , Wolf Andrea , von der Decken Isabel , Rižner Tea Lanišnik , Pavlič Renata , Meshcheryakova Anastasia , Mechtcheriakova Diana , Fritzer-Szekeres Monika , Thalhammer Theresia , Jäger Walter
Published: January 2020

High-grade serous ovarian cancer (HGSOC) is currently treated with cytoreductive surgery and platinum-based chemotherapy. The majority of patients show a primary response; however, many rapidly develop drug resistance. Antiestrogens have been studied as low toxic treatment options for HGSOC, with higher response rates in platinum-sensitive cases. Mechanisms for this difference in response remain unknown. Therefore, the present study investigated the impact of platinum resistance on steroid metabolism in six established HGSOC cell lines sensitive and resistant against carboplatin using a high-resolution mass spectrometry assay to simultaneously quantify the ten main steroids of the estrogenic metabolic pathway. An up to 60-fold higher formation of steroid hormones and their sulfated or glucuronidated metabolites was observed in carboplatin-sensitive cells, which was reversible by treatment with interleukin-6 (IL-6). Conversely, treatment of carboplatin-resistant cells expressing high levels of endogenous IL-6 with the monoclonal anti-IL-6R antibody tocilizumab changed their status to “platinum-sensitive”, exhibiting a decreased IC50 value for carboplatin, decreased growth, and significantly higher estrogen metabolism. Analysis of these metabolic differences could help to detect platinum resistance in HGSOC patients earlier, thereby allowing more efficient interventions.
The Association of IL-1 and HRAS Gene Polymorphisms with Breast Cancer Susceptibility in a Jordanian Population of Arab Descent: A Genotype–Phenotype Study
Authors: AL-Eitan Laith N. , Al-Ahmad Bashar H. , Almomani Fouad A.
Published: January 2020

Breast cancer (BC) pathogenesis is poorly understood and not yet completely determined. BC susceptibility genes are responsible for 20% to 25% of breast cancer risk. The main objective of this study is to identify the genetic polymorphisms within the Harvey rat sarcoma viral oncogene homolog (HRAS1) and interleukin-1 receptor antagonist (IL1-Ra) genes in Jordanian BC female patients and to investigate the genetic association of these polymorphisms with BC. Samples were collected from 150 Jordanian BC patients and 187 healthy age-matched controls. PCR and PCR-RFLP techniques were used to identify genetic polymorphisms within these candidate genes. The single nucleotide polymorphism single nucleotide polymorphism (SNP) association web tool SNPStats (v. 3.6) was used to investigate the allelic and genotypic association with BC. Different statistical analyses were used to study the correlation between the investigated genetic variants and several prognosis factors of BC. A genetic association between BC susceptibility and Il-1β rs1143634 was found specifically at the allelic level of E1 as a risk allele (72% in the cases vs. 64.2% in the controls). Another genetic association was found in the IL-Ra gene (86-VNTR (variable number tandem repeat)), which presented one repeat allele (24.1% in cases vs. 15.59% in controls) and could be considered as a risk allele in Jordanian women. In contrast, this study found that there is no genetic association between Il-1β SNP rs16944 and BC. In addition, a significant association was found between the allelic level of the HRAS1 gene and BC susceptibility. Since this study is the first to be conducted on the genetic susceptibility of these genes to BC in the Jordanian population, more investigations on the link between BC and these variants are recommended to determine the impact of these polymorphisms on other ethnic groups.
Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis
Authors: Suwa Kanehiko , Yamaguchi Takashi , Yoshida Katsunori , Murata Miki , Ichimura Mayuko , Tsuneyama Koichi , Seki Toshihito , Okazaki Kazuichi
Published: January 2020

Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) sometimes occurs in mildly fibrotic livers, while HCC incidence in NASH-related cirrhosis is lower than and less predictable than in hepatitis C virus (HCV)-related cirrhosis. Transforming growth factor (TGF)-β signaling in hepatocytic nuclei is implicated in fibrosis and carcinogenesis. TGF-βtype I receptor (TβRI) and c-Jun N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3, resulting in 2 distinct phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). In mature hepatocytes, oncogenic signaling via the JNK/pSmad3L pathway antagonizes signaling via the tumor-suppressive TβRI/pSmad3C pathway. We immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 NASH patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. HCC occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. In contrast, HCC developed in 12 of 15 NASH patients with limited pSmad3C but only 1 of 15 with abundant pSmad3C. Two of fourteen NASH patients with mild fibrosis developed HCC, their hepatocytic nuclei showed abundant pSmad3L and limited pSmad3C. Five of sixteen patients with severe fibrosis did not develop HCC, their hepatocytic nuclei showed limited pSmad3L and abundant pSmad3C. Smad phospho-isoforms may represent important biomarkers predicting HCC in NASH and potential therapeutic targets for preventing NASH-related HCC.
Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers
Authors: Do Ha Thi Thu , Lee Chang Hoon , Cho Jungsook
Published: January 2020

Chemokines are chemotactic cytokines that mediate immune cell chemotaxis and lymphoid tissue development. Recent advances have indicated that chemokines and their cognate receptors play critical roles in cancer-related inflammation and cancer progression. On the basis of these findings, the chemokine system has become a new potential drug target for cancer immunotherapy. In this review, we summarize the essential roles of the complex network of chemokines and their receptors in cancer progression. Furthermore, we discuss the potential value of the chemokine system as a cancer prognostic marker. The chemokine system regulates the infiltration of immune cells into the tumor microenvironment, which induces both pro- and anti-immunity and promotes or suppresses tumor growth and proliferation, angiogenesis, and metastasis. Increasing evidence indicates the promising prognostic value of the chemokine system in cancer patients. While CCL2, CXCL10, and CX3CL1/CX3CR1 can serve as favorable or unfavorable prognostic factors depending on the cancer types, CCL14 and XCL1 possess good prognostic value. Other chemokines such as CXCL1, CXCL8, and CXCL12 are poor prognostic markers. Despite vast advances in our understanding of the complex nature of the chemokine system in tumor biology, knowledge about the multifaceted roles of the chemokine system in different types of cancers is still limited. Further studies are necessary to decipher distinct roles within the chemokine system in terms of cancer progression and to validate their potential value in cancer prognosis.
HSP90 Interacts with the Fibronectin N-terminal Domains and Increases Matrix Formation
Authors: Chakraborty Abir , Boel Natasha Marie-Eraine , Edkins Adrienne Lesley
Published: January 2020

Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that controls the function and stability of a wide range of cellular client proteins. Fibronectin (FN) is an extracellular client protein of HSP90, and exogenous HSP90 or inhibitors of HSP90 alter the morphology of the extracellular matrix. Here, we further characterized the HSP90 and FN interaction. FN bound to the M domain of HSP90 and interacted with both the open and closed HSP90 conformations; and the interaction was reduced in the presence of sodium molybdate. HSP90 interacted with the N-terminal regions of FN, which are known to be important for matrix assembly. The highest affinity interaction was with the 30-kDa (heparin-binding) FN fragment, which also showed the greatest colocalization in cells and accommodated both HSP90 and heparin in the complex. The strength of interaction with HSP90 was influenced by the inherent stability of the FN fragments, together with the type of motif, where HSP90 preferentially bound the type-I FN repeat over the type-II repeat. Exogenous extracellular HSP90 led to increased incorporation of both full-length and 70-kDa fragments of FN into fibrils. Together, our data suggested that HSP90 may regulate FN matrix assembly through its interaction with N-terminal FN fragments.
Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells
Authors: Yue Lili , Wang Liuqing , Du Yangchun , Zhang Wei , Hamada Kozo , Matsumoto Yoshifumi , Jin Xi , Zhou Yandong , Mikoshiba Katsuhiko , Gill Donald L. , Han Shengcheng , Wang Youjun
Published: January 2020

Being the largest the Ca2+ store in mammalian cells, endoplasmic reticulum (ER)-mediated Ca2+ signalling often involves both Ca2+ release via inositol 1, 4, 5-trisphosphate receptors (IP3R) and store operated Ca2+ entries (SOCE) through Ca2+ release activated Ca2+ (CRAC) channels on plasma membrane (PM). IP3Rs are functionally coupled with CRAC channels and other Ca2+ handling proteins. However, it still remains less well defined as to whether IP3Rs could regulate ER-mediated Ca2+ signals independent of their Ca2+ releasing ability. To address this, we generated IP3Rs triple and double knockout human embryonic kidney (HEK) cell lines (IP3Rs-TKO, IP3Rs-DKO), and systemically examined ER Ca2+ dynamics and CRAC channel activity in these cells. The results showed that the rate of ER Ca2+ leakage and refilling, as well as SOCE were all significantly reduced in IP3Rs-TKO cells. And these TKO effects could be rescued by over-expression of IP3R3. Further, results showed that the diminished SOCE was caused by NEDD4L-mediated ubiquitination of Orai1 protein. Together, our findings indicate that IP3R3 is one crucial player in coordinating ER-mediated Ca2+ signalling.
Extracellular Vesicles Derived from Human Gingival Mesenchymal Stem Cells: A Transcriptomic Analysis
Authors: Silvestro Serena , Chiricosta Luigi , Gugliandolo Agnese , Pizzicannella Jacopo , Diomede Francesca , Bramanti Placido , Trubiani Oriana , Mazzon Emanuela
Published: January 2020

Human gingival mesenchymal stem cells (hGMSCs) have outstanding characteristics of proliferation and are able to differentiate into osteogenic, chondrogenic, adipogenic, and neurogenic cell lineages. The extracellular vesicles (EVs) secreted by hGMSCs contain proteins, lipids, mRNA and microRNA have emerged as important mediators of cell-to-cell communication. In this study, we analyzed the transcriptome of hGMSCs-derived EVs using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 26 structural protein classes and the presence of “non-coding RNAs”. Our results showed that EVs contain several growth factors such as Transforming Growth Factor-β (TGF-β), Fibroblast Growth Factor (FGF), and Vascular Endothelial Growth Factors (VEGF) implicated in osteoblast differentiation and in angiogenetic process. Furthermore, the transcriptomic analysis showed the presence of glial cell-derived neurotrophic factor (GDNF) family ligands and neurotrophins involved in neuronal development. The NGS analysis also identified the presence of several interleukins among which some with anti-inflammatory action. Moreover, the transcriptome profile of EVs contained members of the Wnt family, involved in several biological processes, such as cellular proliferation and tissue regeneration. In conclusion, the huge amount of growth factors included in the hGMSCs-derived EVs could make them a big resource in regenerative medicine.
Selection of the Reference Gene for Expression Normalization in Papaver somniferum L. under Abiotic Stress and Hormone Treatment
Authors: Zhang Zhaoping , Li Changjian , Zhang Junqing , Chen Fang , Gong Yongfu , Li Yanrong , Su Yujie , Wei Yujie , Zhao Yucheng
Published: January 2020

Papaver somniferum L. is an important medical plant that produces analgesic drugs used for the pain caused by cancers and surgeries. Recent studies have focused on the expression genes involved in analgesic drugs biosynthesis, and the real-time quantitative polymerase chain reaction (RT-qPCR) technique is the main strategy. However, no reference genes have been reported for gene expression normalization in P. somniferum. Herein, nine reference genes (actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin 2 (CYP2), elongation factor 1-alpha (EF-1α), glyceraldehyde-3-phosphate dehydrogenase 2, cytosolic (GAPC2), nuclear cap-binding protein subunit 2 (NCBP2), protein phosphatase 2A (PP2A), TIP41-like protein (TIP41), and tubulin beta chain (TUB)) of P. somniferum were selected and analyzed under five different treatments (cold, drought, salt, heavy metal, and hormone stress). Then, BestKeeper, NormFinder, geNorm, and RefFinder were employed to analyze their gene expression stability. The results reveal that NCBP2 is the most stable reference gene under various experimental conditions. The work described here is the first report regarding on reference gene selection in P. somniferum, which could be used for the accurate normalization of the gene expression involved in analgesic drug biosynthesis.
Imaging Mitochondrial Functions: From Fluorescent Dyes to Genetically-Encoded Sensors
Authors: Gökerküçük Elif Begüm , Tramier Marc , Bertolin Giulia
Published: January 2020

Mitochondria are multifunctional organelles that are crucial to cell homeostasis. They constitute the major site of energy production for the cell, they are key players in signalling pathways using secondary messengers such as calcium, and they are involved in cell death and redox balance paradigms. Mitochondria quickly adapt their dynamics and biogenesis rates to meet the varying energy demands of the cells, both in normal and in pathological conditions. Therefore, understanding simultaneous changes in mitochondrial functions is crucial in developing mitochondria-based therapy options for complex pathological conditions such as cancer, neurological disorders, and metabolic syndromes. To this end, fluorescence microscopy coupled to live imaging represents a promising strategy to track these changes in real time. In this review, we will first describe the commonly available tools to follow three key mitochondrial functions using fluorescence microscopy: Calcium signalling, mitochondrial dynamics, and mitophagy. Then, we will focus on how the development of genetically-encoded fluorescent sensors became a milestone for the understanding of these mitochondrial functions. In particular, we will show how these tools allowed researchers to address several biochemical activities in living cells, and with high spatiotemporal resolution. With the ultimate goal of tracking multiple mitochondrial functions simultaneously, we will conclude by presenting future perspectives for the development of novel genetically-encoded fluorescent biosensors.
Comparison of Wing, Ovipositor, and Cornus Morphologies between Sirex noctilio and Sirex nitobei Using Geometric Morphometrics
Authors: Wang Ming , Wang Lixiang , Fu Ningning , Gao Chenglong , Ao Tegen , Ren Lili , Luo Youqing
Published: January 2020

Sirex noctilio F. (Hymenoptera: Siricidae) is an invasive woodwasp from Europe and North Africa. Globalization has led to an expanding global presence in pine forests. S. noctilio has been previously introduced outside of its native range and now co-occurs in trees with native S. nitobei Matsumura (first discovered in 2016). Damage to Pinus sylvestris var. mongolica Litv in northeast China can be attributed to two types of woodwasp. To distinguish the two species by the traditional taxonomic morphology, we mainly differentiate the color of the male’s abdomen and the female’s leg. There remains intraspecific variation like leg color in the delimitation of related genera or sibling species of Sirex woodwasps. In this study, we used landmark-based geometric morphometrics including principal component analysis, canonical variate analysis, thin-plate splines, and cluster analysis to analyze and compare the wings, ovipositors, and cornus of two woodwasps to ascertain whether this approach is reliable for taxonomic studies of this group. The results showed significant differences in forewing venation and the shapes of pits in the middle of ovipositors among the two species, whereas little difference in hindwings and cornus was observed. This study assists in clarifying the taxonomic uncertainties of Siricidae and lays a foundation for further studies of the interspecific relationships of the genus Sirex.
An Integrated Approach to Study the Morphodynamics of the Lignano Tidal Inlet
Authors: Petti Marco , Bosa Silvia , Pascolo Sara , Uliana Erika
Published: January 2020

The morphological evolution of a tidal inlet is the combined result of tides and wind waves, which interact in a non-linear manner and over very different time-scales. Likewise, the presence of maritime structures built in the vicinity of the tidal inlet, for coastal or port defense or to stabilize the inlet itself, can greatly affect this dynamic equilibrium, changing erosional and depositional patterns of the adjacent shoreline. In this study, the narrowing phenomenon of the Lignano tidal inlet subsequent to the construction of the related port, is examined through an integrated approach in order to propose and verify a possible form of evolution. This approach is the result of the combination of three methods: the historical reconstruction of the shifting of the coastline, an empirical scheme which describes the qualitative morphology of a mixed-energy tidal inlet, and a process-based morphodynamic modeling, which adopts a bi-dimensional depth averaged (2DH) approach. The application of numerical modeling has required the definition of a reduced input set of data representing an average year, in particular for wind and tidal conditions, including the meteorological component. The magnitude and the directions of the simulated dominant sediment transport are coherent with real processes both from a qualitative and a quantitative point of view.