Search results for: immunohistochemical markers

Authors: Yiding Qu, Svetlana V. Komarova

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Chemokines acting through their cognate chemokine receptors guide the directional migration of the cell along the chemokine gradient. Several chemokine receptors were recently identified as non-signaling (decoy), based on their ability to bind the chemokine but produce no measurable signal in the cell. The function of these decoy receptors is not well understood. We examined the expression of a decoy receptor CCRL1 and a signaling receptor that binds to the same ligands, CCR7, in prostate cancer using publically available microarray data (www.oncomine.org). The expression of both CCRL1 and CCR7 increased in an approximately half of prostate carcinoma samples and the majority of metastatic cancer samples compared to normal prostate. Moreover, the expression of CCRL1 positively correlated with the expression of CCR7. These data suggest that CCR7 and CCRL1 can be used as clinical markers for the early detection of transformation from carcinoma to metastatic cancer. In addition, these data support our hypothesis that the non-signaling chemokine receptors actively stimulate cell migration.

Keywords: bioinformatics, cell migration, decoy receptor, meta-analysis, prostate cancer

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Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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Authors: Ankur Mundhra, Shubhadeep Chakraborty, Y. R. Singh, Vishal Das

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Seismic data scaling affects the dynamic range of a data and with present day lower costs of storage and higher reliability of Hard Disk data, scaling is not suggested. However, in dealing with data of different vintages, which perhaps were processed in 16 bits or even 8 bits and are need to be processed with 32 bit available data, scaling is performed. Also, scaling amplifies low amplitude events in deeper region which disappear due to high amplitude shallow events that saturate amplitude scale. We have focused on significance of scaling data to aid interpretation. This study elucidates a proper seismic loading procedure in workstations without using default preset parameters as available in most software suites. Differences and distribution of amplitude values at different depth for seismic data are probed in this exercise. Proper loading parameters are identified and associated steps are explained that needs to be taken care of while loading data. Finally, the exercise interprets the un-certainties which might arise when correlating scaled and unscaled versions of seismic data with synthetics. As, seismic well tie correlates the seismic reflection events with well markers, for our study it is used to identify regions which are enhanced and/or affected by scaling parameter(s).

Keywords: clipping, compression, resolution, seismic scaling

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Stephen Tullis, M. David DiDonato, Hong Sung Park

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Rowing boats (shells) are often steered by a small rudder operated by one of the backward-facing rowers; the attention required of that athlete then slightly decreases the power that that athlete can provide. Reducing the steering distraction would then increase the overall boat speed. Races are straight 2000 m courses with each boat in a 13.5 m wide lane marked by small (~15 cm) widely-spaced (~10 m) buoys, and the boat trajectory is affected by both cross-currents and winds. An optical buoy recognition and tracking system has been developed that provides the boat’s location and orientation with respect to the lane edges. This information is provided to the steering athlete as either: a simple overlay on a video display, or fed to a simplified autopilot system giving steering directions to the athlete or directly controlling the rudder. The system is then effectively a “lane-assist” device but with small, widely-spaced lane markers viewed from a very shallow angle due to constraints on camera height. The image is captured with a lightweight 1080p webcam, and most of the image analysis is done in OpenCV. The colour RGB-image is converted to a grayscale using the difference of the red and blue channels, which provides good contrast between the red/yellow buoys and the water, sky, land background and white reflections and noise. Buoy detection is done with thresholding within a tight mask applied to the image. Robust linear regression using Tukey’s biweight estimator of the previously detected buoy locations is used to develop the mask; this avoids the false detection of noise such as waves (reflections) and, in particular, buoys in other lanes. The robust regression also provides the current lane edges in the camera frame that are used to calculate the displacement of the boat from the lane centre (lane location), and its yaw angle. The interception of the detected lane edges provides a lane vanishing point, and yaw angle can be calculated simply based on the displacement of this vanishing point from the camera axis and the image plane distance. Lane location is simply based on the lateral displacement of the vanishing point from any horizontal cut through the lane edges. The boat lane position and yaw are currently fed what is essentially a stripped down marine auto-pilot system. Currently, only the lane location is used in a PID controller of a rudder actuator with integrator anti-windup to deal with saturation of the rudder angle. Low Kp and Kd values decrease unnecessarily fast return to lane centrelines and response to noise, and limiters can be used to avoid lane departure and disqualification. Yaw is not used as a control input, as cross-winds and currents can cause a straight course with considerable yaw or crab angle. Mapping of the controller with rudder angle “overall effectiveness” has not been finalized - very large rudder angles stall and have decreased turning moments, but at less extreme angles the increased rudder drag slows the boat and upsets boat balance. The full system has many features similar to automotive lane-assist systems, but with the added constraints of the lane markers, camera positioning, control response and noise increasing the challenge.

Keywords: auto-pilot, lane-assist, marine, optical, rowing

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Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang

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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.

Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree

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Authors: Eun Gyeong Lee, Ji Young Park, Hyun Ae Woo

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Reactive oxygen species (ROS) production is involved in ischemia/reperfusion (I/R) injury in kidney of mice. Oxidative stress develops from an imbalance between ROS production and reduced antioxidant defenses. Many enzymatic and nonenzymatic antioxidant systems including peroxiredoxins (Prxs) are present in kidney to maintain an appropriate level of ROS and prevent oxidative damage. Prxs are a family of peroxidases that reduce peroxides, with a conserved cysteine residue serving as the site of oxidation by peroxides. In this study, we examined the protective role of Prx V against I/R-induced acute kidney injury (AKI) using Prx V wild type (WT) and knockout (KO) mice. We compared the response of Prx V WT and KO mice in mice model of I/R injury. Renal structure, functions, oxidative stress markers, protein levels of oxidative damage marker were worse in Prx V KO mice. Ablation of Prx V enhanced susceptibility to I/R-induced oxidative stress. Prx V KO mice were seen to have more severe renal damage than Prx V WT mice in mice model of I/R injury. Our results demonstrate that Prx V is protective against I/R-induced AKI.

Keywords: peroxiredoxin, ischemia/reperfusion, kidney, oxidative stress

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Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li

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Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.

Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Zehor Ktitni

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In pragmatics, politeness is regarded as a feature of paramount importance to successful interpersonal relationships. On the other hand, emails have recently become one of the indispensable means of communication in educational settings. This research puts email communication at the core of the study and analyses it from a politeness perspective. More specifically, it endeavours to look closely at how the concept of (im)politeness is reflected through students’ emails. To this end, a corpus of Algerian supervisees’ email threads, exchanged with their Irish supervisors, was compiled. Leech’s model of politeness (2014) was selected as the main theoretical framework of this study, in addition to making reference to Brown and Levinson’s model (1987) as it is one of the most influential models in the area of pragmatic politeness. Further, some follow-up interviews are to be conducted with Algerian students to reinforce the results derived from the corpus. Initial findings suggest that Algerian Ph.D. students’ emails tend to include more politeness markers than impoliteness ones, they heavily make use of academic titles when addressing their supervisors (Dr. or Prof.), and they rely on hedging devices in order to sound polite.

Keywords: politeness, email communication, corpus pragmatics, Algerian PhD supervisees, Irish supervisors

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Authors: Metin Çenesi̇z, Büşra Şahi̇n

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The sustainability of aquaculture is possible through the conscious use of resources and minimization of environmental impacts. These can be achieved through science-based planning, ecosystem-based management, strict observations and controls. The ideal water temperature for rainbow trout, which are intensively farmed in the Black Sea Region of Turkey, should be below 20 oC. In summer, the water temperature exceeds this value in some dams where production is carried out. For this reason, it has become obligatory to transfer to dams where the water temperature is low in order to provide suitable temperature conditions. There are many factors that may cause stress to trout during transportation. Some of these stress factors are starvation of the fish for a while to avoid contamination of the water, mobility and noise during transportation and loading, dissolved oxygen content and composition of the water in the transportation tanks, etc. The starvation stress caused by starvation/lack of food during transportation causes a certain amount of loss of macronutrients such as carbohydrates, proteins and fats in the tissues. This situation causes changes in metabolic activities and the energy balance of fish species. In this study, oxidant-antioxidant values and stress markers of rainbow trout starved before transplantation will be evaluated.

Keywords: oncorhynchus mykiss, starvation stress, TAS, TOS

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Authors: Alexis John de Britto

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Studies were performed to select the superior genotypes based on intra-specific variations, caused by phytogeographical, climatic and edaphic parameters of three anti cancer drug yielding mangrove plants such as Acanthus ilicifolius L., Calophyllum inophyllum L. and Excoecaria agallocha L. using ISSR (Inter Simple Sequence Repeats) markers and phytochemical analysis such as preliminary phytochemical tests, TLC, HPTLC, HPLC and antioxidant tests. The plants were collected from five different geographical locations of the East Coast of south India. Genetic heterozygosity, Nei’s gene diversity, Shannon’s information index and Percentage of polymorphism between the populations were calculated using POPGENE software. Cluster analysis was performed using UPGMA algorithm. AMOVA and correlations between genetic diversity and soil factors were analyzed. Combining the molecular and phytochemical variations superior genotypes were selected. Conservation constraints and methods of efficient exploitation of the species are discussed.

Keywords: anti-cancer drug yielding plants, DNA fingerprinting, phytochemical analysis, selection of superior genotypes

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Authors: H. Oudira, A. Saifi

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The therapeutic utility of certain Auger emitters such as iodine-125 depends on their position within the cell nucleus . Or diagnostically, and to maintain as low as possible cell damage, it is preferable to have radionuclide localized outside the cell or at least the core. One solution to this problem is to consider markers capable of conveying anticancer drugs to the tumor site regardless of their location within the human body. The objective of this study is to simulate the impact of a complex such as bleomycin on single and double strand breaks in the DNA molecule. Indeed, this simulation consists of the following transactions: - Construction of BLM -Fe- DNA complex. - Simulation of the electron’s transport from the metastable state excitation of Fe 57 by the Monte Carlo method. - Treatment of chemical reactions in the considered environment by the diffusion equation. For physical, physico-chemical and finally chemical steps, the geometry of the complex is considered as a sphere of 50 nm centered on the binding site , and the mathematical method used is called step by step based on Monte Carlo codes.

Keywords: concentration, yield, radical species, bleomycin, excitation, DNA

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Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Rupak Kumar Sarma, Ratul Saikia

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Macrophytes encompass major functional group in eutrophic wetland ecosystems. As a key functional element of freshwater lakes, they play a crucial role in regulating various wetland biogeochemical cycles, as well as maintain the biodiversity at the ecosystem level. The high carbon-rich underground biomass of macrophyte populations may harbour diverse microbial community having significant potential in maintaining different biogeochemical cycles. The present investigation was designed to study the macrophyte-microbe interaction in coupled nitrification and denitrification, considering Deepor Beel Lake (a Ramsar conservation site) of North East India as a model eutrophic system. Highly eutrophic sites of Deepor Beel were selected based on sediment oxygen demand and inorganic phosphorus and nitrogen (P&N) concentration. Sediment redox potential and depth of the lake was chosen as the benchmark for collecting the plant and sediment samples. The average highest depth in winter (January 2016) and summer (July 2016) were recorded as 20ft (6.096m) and 35ft (10.668m) respectively. Both sampling depth and sampling seasons had the distinct effect on variation in macrophyte community composition. Overall, the dominant macrophytic populations in the lake were Nymphaea alba, Hydrilla verticillata, Utricularia flexuosa, Vallisneria spiralis, Najas indica, Monochoria hastaefolia, Trapa bispinosa, Ipomea fistulosa, Hygrorhiza aristata, Polygonum hydropiper, Eichhornia crassipes and Euryale ferox. There was a distinct correlation in the variation of major sediment physicochemical parameters with change in macrophyte community compositions. Quantitative estimation revealed an almost even accumulation of nitrate and nitrite in the sediment samples dominated by the plant species Eichhornia crassipes, Nymphaea alba, Hydrilla verticillata, Vallisneria spiralis, Euryale ferox and Monochoria hastaefolia, which might have signified a stable nitrification and denitrification process in the sites dominated by the selected aquatic plants. This was further examined by a systematic analysis of microbial populations through culture dependent and independent approach. Culture-dependent bacterial community study revealed the higher population of nitrifiers and denitrifiers in the sediment samples dominated by the six macrophyte species. However, culture-independent study with bacterial 16S rDNA V3-V4 metagenome sequencing revealed the overall similar type of bacterial phylum in all the sediment samples collected during the study. Thus, there might be the possibility of uneven distribution of nitrifying and denitrifying molecular markers among the sediment samples collected during the investigation. The diversity and abundance of the nitrifying and denitrifying molecular markers in the sediment samples are under investigation. Thus, the role of different aquatic plant functional types in microorganism mediated nitrogen cycle coupling could be screened out further from the present initial investigation.

Keywords: denitrification, macrophyte, metagenome, microorganism, nitrification

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

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The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: James M. Geidner

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Objective: The purpose of this meta-analysis was to examine the evidence for the effectiveness of exercise interventions on reducing metabolic components in children and/or adolescents diagnosed with Paediatric Metabolic Syndrome. Methods: A computerized search was made from four databases: PubMed, PsycInfo, SPORTDiscus, Cochrane Central Register. The analysis was restricted to children and adolescents with metabolic syndrome examining the effect of exercise interventions on metabolic components. Effect size and 95% confidence interval were calculated and the heterogeneity of the studies was estimated using Cochran’s Q-statistic and I2. Bias was assessed using multiple tools and statistical analyses. Results: Thirteen studies, consisting of 19 separate trials, were selected for the meta-analysis as they fulfilled the inclusion criteria (n=908). Exercise interventions resulted in decreased waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, insulin resistance, triglycerides, and High-Density Lipoprotein Cholesterol (HDL-C). Conclusions: This meta-analysis provides insights into the effectiveness of exercise interventions on markers of Paediatric Metabolic Syndrome in children and adolescents.

Keywords: metabolic syndrome, syndrome x, pediatric, meta-analysis

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Authors: Tamar Beridze, Elisa Boscari, Fleur Scheele, Tamari Edisherashvili, Cort Anderson, Leonardo Congiu

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The eastern part of the Black Sea and its tributaries are suitable habitats for several sturgeon species, among which Acipenser gueldenstaedtii, A. stellatus, A. nudiventris, A. persicus, A. sturio, and H. huso are well documented. However, different threats have led these species to a dramatic decline; all of them are currently listed as Critically Endangered and some Locally Extinct in that area. We tested 94 wild sturgeon samples from the Black Sea and Rioni River by analyzing the mitochondrial Control Region and nuclear markers for hybrid identification. The data analyses (1) assessed mitochondrial diversity among samples, (2) identified their species, as well as (3) indicated instances of hybridization. The data collected, besides confirming a sharp decrease of catches of Beluga and Stellate sturgeon in recent years, also revealed four juvenile hybrids between Russian and Stellate sturgeon, providing the first evidence of natural interspecific hybridization in the Rioni. The present communication raises concerns about the status of sturgeon species in this area and underlines the urgent need for conservation programs to restore self-sustaining populations.

Keywords: black sea, sturgeon, Rioni river, interspecific hybridization

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Fatmawati Adam, Saidatul Syaima Mat Tari, Saiful Nizam Tajuddin, Nurul Salwa Azliyana Hamzah

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Essential oil of agarwood or known as Gaharu in Malay is highly prized for its value as luxury fragrances and incense. However, the complexities of the chemical composition of agarwood itself is the main challenge for establishment of an effective recovery method, which is able to ensure uniform qualities and standard for each batch of essential oil production. Agarwood markers are actually a blend of volatile and non-volatile compounds. While volatile molecules could be easily retrieved by the present distillation technique, the high solubility properties are the limiting factor for the latter. With regard to this, an elementary chemistry resolution study had been performed on commercial agarwood essential oil-water mixture, by the application of preparative HPLC and FTIR. Interpretation of the results leads to the theoretical postulation that, agarwood water mixture comprise of agarospirol, jinkohol, jinkoh eremol and khusenol. This study provides a pinpoint on the chemical characteristics of water soluble (non-volatile) agarwood compounds, therefore, will be an insight for researchers to develop a more strategic technique for their extraction. Thereafter the optimum quality of this essential oil could be controlled in a more improved way.

Keywords: Agarwood, Aquillaria Malaccensis, agarospirol, jinkohol, jinkoh eremol, khusenol

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Authors: Ozhan Simsek, Dicle Donmez, Burhanettin Imrak, Ahsen Isik Ozguven, Yildiz Aka Kacar

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Pomegranate (Punica granatum L.) is known to be one of the oldest edible fruit tree species, with a wide geographical global distribution. Fruits from the two defined varieties (Hicaznar and 33N26) were taken at intervals after pollination and fertilization at different sizes. Seed samples were used for transcriptome sequencing. Primary sequencing was produced by Illumina Hi-Seq™ 2000. Firstly, we had raw reads, and it was subjected to quality control (QC). Raw reads were filtered into clean reads and aligned to the reference sequences. De novo analysis was performed to detect genes expressed in seeds of pomegranate varieties. We performed downstream analysis to determine differentially expressed genes. We generated about 27.09 gb bases in total after Illumina Hi-Seq sequencing. All samples were assembled together, we got 59,264 Unigenes, the total length, average length, N50, and GC content of Unigenes are 84.547.276 bp, 1.426 bp, 2,137 bp, and 46.20 %, respectively. Unigenes were annotated with 7 functional databases, finally, 42.681(NR: 72.02%), 39.660 (NT: 66.92%), 30.790 (Swissprot: 51.95%), 20.212 (COG: 34.11%), 27.689 (KEGG: 46.72%), 12.328 (GO: 20.80%), and 33,833 (Interpro: 57.09%) Unigenes were annotated. With functional annotation results, we detected 42.376 CDS, and 4.999 SSR distribute on 16.143 Unigenes.

Keywords: next generation sequencing, SSR, RNA-Seq, Illumina

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Authors: Muhammad Tarmidzi, Reza M. G. Gani, Andri Luthfi

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The purpose of this study is to identify rock zone containing hydrocarbons with calculating rock property includes volume shale, total porosity, effective porosity and water saturation. Identification method rock property based on GR log, resistivity log, neutron log and density rock. Zoning is based on sequence stratigraphic markers that are sequence boundary (SB), transgressive surface (TS) and flooding surface (FS) which correlating ten well log in blok “M”. The results of sequence stratigraphic correlation consist of eight zone that are two LST zone, three TST zone and three HST zone. The result of rock property calculation in each zone is showing two LST zone containing hydrocarbons. LST-1 zone has average volume shale (Vsh) 25%, average total porosity (PHIT) 14%, average effective porosity (PHIE) 11% and average water saturation 0,83. LST-2 zone has average volume shale (Vsh) 19%, average total porosity (PHIT) 21%, average effective porosity (PHIE) 17% and average water saturation 0,82.

Keywords: hydrocarbons zone, petrophysic, rock property, sequence stratigraphic

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Authors: Muhammad Mohsan, Mehboob Ur-Rahman, Sana Zulfiqar, Shumila Ashfaq

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Brown Rust (Puccinia triticina), also known as leaf rust, pose a serious threat to wheat cultivation in the world. Nine candidate wheat lines/mutants were subjected to rust inoculation, lodging and aphid population in vivo conditions. Four lines/mutants (E-284, E-505, 2008-6 MR and 2008-14MR) were found resistant to leaf rust attack. Two lines (PGMB 15-29 and 2011-1 MR) displayed moderately resistant reactions against the disease. Three lines/mutants were depicted as susceptible to leaf rust. The lowest population of aphids, i.e., 16.67, was observed on 2008-14MR. Three lines/mutants (NN1-47, NN1-89 and PGMB 15-29) were found under zero level of lodging. The presence and absence of different leaf rust-resistant genes like Lr13, Lr34, Lr46 and Lr67 were assessed with the help of molecular markers. All the wheat lines/mutants were found loaded with leaf rust-resistant genes such as Lr13 and Lr 34, while Lr46 and Lr67 were found in 66% of wheat lines/mutants. The resistant source can be exploited in the breeding program to develop rust, aphid and lodging with race-nonspecific resistant wheat variety.

Keywords: wheat, leaf rust, lodging, aphid

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Authors: Chen Wang, Chun Liang

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Microsatellite instability (MSI) is characterized by high degree of polymorphism in microsatellite (MS) length due to a deficiency in mismatch repair (MMR) system. MSI is associated with several tumor types and its status can be considered as an important indicator for tumor prognostic. Conventional clinical diagnosis of MSI examines PCR products of a panel of MS markers using electrophoresis (MSI-PCR) which is laborious, time consuming, and less reliable. MSIpred, a python 2 package for automatic classification of MSI was released by this study. It computes important somatic mutation features from files in mutation annotation format (MAF) generated from paired tumor-normal exome sequencing data, subsequently using these to predict tumor MSI status with a support vector machine (SVM) classifier trained by MAF files of 1074 tumors belonging to four types. Evaluation of MSIpred on an independent 358-tumor test set achieved overall accuracy of over 98% and area under receiver operating characteristic (ROC) curve of 0.967. These results indicated that MSIpred is a robust pan-cancer MSI classification tool and can serve as a complementary diagnostic to MSI-PCR in MSI diagnosis.

Keywords: microsatellite instability, pan-cancer classification, somatic mutation, support vector machine

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Authors: Diriba Dereje

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Background: Cardiac and renal disease are the most prevalent chronic non-communicable diseases (CNCD) affecting the community in a significant manner. The best and recommended method in halting CNCD is by working on prevention as early as possible. This is only possible if early surrogate markers are identified. As part of the stated solution, this study will identify an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Objective: The main aim of this study was to assess an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Methodology: Community based cross sectional study was conducted among 384 adult in Jimma town. A systematic sampling technique was used in selecting participants to the study. In searching for the possible association, binary and multivariate logistic regression and t-test was conducted. Finally, the association between microalbuminuria and lung function test was well stated in the form of figures and written description. Result and Conclusion: A significant association was found between microalbuminuria and different lung function test parameters.

Keywords: microalbuminuria, lung function, association, test

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Authors: Dilani Wimalasiri, Robert Brkljaca, Sylvia Urban, Terrence Piva, Tien Huynh

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Momordica cochinchinensis (Cucurbitaceae) is used as food and traditional medicine in South East Asia and is commonly known as Red Gac. The fruit aril consists 70 times higher lycopene and 10 times higher β-carotene than all known fruits and vegetables. Despite its nutritional value there is little information available on its genetic variation and its influence on nutritional value. In this study; genetic and nutritional variation (lycopene and β-carotene) was investigated among 47 M. cochinchinensis samples collected from Australia, Thailand and Vietnam using molecular markers (RAPD and ISSR) and HPLC, respectively. UPGMA based cluster analysis of genetic data grouped Northern and Central Vietnam samples together but were separated from Australia, Thailand and Southern Vietnam samples. The concentration of lycopene was significantly higher among the samples collected from Central Vietnam (p<0.05) and the concentration of β-carotene was significantly higher among the samples collected from Northern Vietnam (p<0.05) indicating the existence of best varieties. This study provides vital information in genetic diversity and facilitates the selection and breeding for nutritious M. cochinchinensis varieties.

Keywords: momordica cochinchinensis, lycopene, beta carotene, genetic diversity

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Authors: Aniruddha Kulkarni

Abstract:

In very few cases of external hernias we require imaging modalities as on most occasions clinical examination tests are good enough. Ultrasound will help in chronic abdominal or groin pain, equivocal clinical results & complicated hernias. Ultrasound is useful in assessment of cause of raised intrabdominal pressure. In certain cases will comment about etiology, complications and chronicicty of lesion. Screening of rest of abdominal organs too is important advantage being real time modality. Cost effectiveness, no radiation allows modality be used repeatedly in indicated cases. Sonography is better accepted by patients too as it is cost effective. Best advanced tissue harmonic equipment and increasing expertise making it popular. Ultrasound can define surgical anatomy, rent size, contents, etiological /recurrence factors in great detail and with authority hence accidental findings in a planned surgical procedure can be easily avoided. Clinical dynamic valselva and reducibility test can better documented by real time ultrasound study. In case of recurrence, Sonography will help in assessing the hernia details better as being dynamic real time investigation. Ultrasound signs in case of internal hernias are well comparable with CT findings.

Keywords: laparoscopic repair, Hernia, CT findings, chronic pain

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Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

Abstract:

Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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