Search results for: cell signaling modulator

Authors: S. H. Borghei, E. Teymourian, M. Mobin, G. M. Komaki, S. Sheikh

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Imperialist competitive algorithm (ICA) is a recent meta-heuristic method that is inspired by the social evolutions for solving NP-Hard problems. The ICA is a population based algorithm which has achieved a great performance in comparison to other meta-heuristics. This study is about developing enhanced ICA approach to solve the cell formation problem (CFP) using sequence data. In addition to the conventional ICA, an enhanced version of ICA, namely EICA, applies local search techniques to add more intensification aptitude and embed the features of exploration and intensification more successfully. Suitable performance measures are used to compare the proposed algorithms with some other powerful solution approaches in the literature. In the same way, for checking the proficiency of algorithms, forty test problems are presented. Five benchmark problems have sequence data, and other ones are based on 0-1 matrices modified to sequence based problems. Computational results elucidate the efficiency of the EICA in solving CFP problems.

Keywords: cell formation problem, group technology, imperialist competitive algorithm, sequence data

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Authors: Retno Supriyanti, Best Leader Nababan, Yogi Ramadhani, Wahyu Siswandari

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Blood cell morphology is an important parameter in a hematology test. Currently, in developing countries, a lot of hematology is done manually, either by physicians or laboratory staff. According to the limitation of the human eye, examination based on manual method will result in a lower precision and accuracy. In addition, the hematology test by manual will further complicate the diagnosis in some areas that do not have competent medical personnel. This research aims to develop a simple tool in the detection of blood cell morphology-based computer. In this paper, we focus on the detection of the outer contour of leukocytes. The results show that the system that we developed is promising for detecting blood cell morphology automatically. It is expected, by implementing this method, the problem of accuracy, precision and limitations of the medical staff can be solved.

Keywords: morphology operation, developing countries, hematology test, limitation of medical personnel

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Authors: Sylwia K. Naliwajko, Justyna Moskwa, Patryk Nowakowski, Renata Markiewicz-Zukowska, Krystyna Gromkowska-Kepka, Anna Puscion-Jakubik, Maria H. Borawska

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Amygdalin is found in many fruit seeds, including apricot, peach, quince, apples, and almonds. Amygdalin (also named vitamin B17), as well as its sources, are commonly used as an alternative therapy or prevention of cancer. The potential activity of amygdalin is related to its enzymatic degradation to the hydrogen cyanide. Hydrogen cyanide is a toxic substance that causes liver and nerves damage, fever, coma or even death. Amygdalin is much better tolerated after intravenous than oral administration. The aim of this study was to examine the influence of amygdalin on glioblastoma multiforme cell lines. Three glioblastoma multiforme cell lines – U87MG, T98, LN18 were incubated (48 h) with amygdalin in concentrations 100, 250, 500, 1000 and 2000 µg/mL. The MTT (Thiazolyl Blue Tetrazolium Bromide) test and DNA binding test by [3H]-thymidine incorporation were used to determine the anti-proliferative activity of amygdalin. The secretion of metalloproteinases (MMP2 and MMP-9) from U87MG cells was estimated by gelatin zymography. The statistical analysis was performed using Statistica v. 13.0 software. The data was presented as a % of control. Amygdalin did not show significant inhibition of viability of all the glioblastoma cells in concentrations 100, 250, 500, 1000 µg/mL. In 2000 µg/mL there were significant differences compared to the control, but inhibition of viability was less than 20% (more than 80% of control). The average viability of U87MG cells was 92,0±4%, T98G: 85,8±3% and LN18: 94,7±2% of the control. There was no dose-response viability, and IC50 value was not recognized. DNA binding in U87MG cells was not inhibited (109,0±3 % of control). After treatment with amygdalin, we observed significantly increased secretion of MMP2 and MMP9 in U87MG cells (130,3±14% and 112,0±5% of control, respectively). Our results suggest that amygdalin has no anticancer activity in glioblastoma cell lines.

Keywords: amygdalin, anticancer, cell line, glioblastoma

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Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

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Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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Authors: Diego Luján Villarreal

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Visual prostheses are designed to repair some eyesight in patients blinded by photoreceptor diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Electrode-to-cell proximity has drawn attention due to its implications on secure single-localized stimulation. Yet, few techniques are available for understanding the relationship between the number of cells activated and the current injection. We propose an answering technique by solving the governing equation for time-dependent electrical currents using finite element discretization to obtain the volume of stimulation.

Keywords: visual prosthetic devices, volume for stimulation, FEM discretization, 3D simulation

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Authors: Forough Ataollahi, Sumit Pramanik, Belinda Pingguan-Murphy, Wan Abu Bakar Bin Wan Abas, Noor Azuan Bin Abu Osman

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Endothelium proliferation is an important process in cardiovascular homeostasis and can be regulated by extracellular environment, as cells can actively sense mechanical environment. In this study, we evaluated endothelial cell proliferation on PDMS/alumina (Al2O3) composites and pure PDMS. The substrates were prepared from pure PDMS and its composites with 5% and 10% Al2O3 at curing temperature 50˚C for 4 h and then characterized by mechanical, structural and morphological analyses. Higher stiffness was found in the composites compared to the pure PDMS substrate. Cell proliferation of the cultured bovine aortic endothelial cells on substrate materials were evaluated via Resazurin assay and 1, 1’-Dioctadecyl-1, 3, 3, 3’, 3’-Tetramethylindocarbocyanine Perchlorate-Acetylated LDL (Dil-Ac-LDL) cell staining, respectively. The results revealed that stiffer substrates promote more endothelial cells proliferation to the less stiff substrates. Therefore, this study firmly hypothesizes that the stiffness elevates endothelial cells proliferation.

Keywords: stiffness, proliferation, bovine aortic endothelial cells, extra cellular matrix, vascular

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Authors: Waleed Alsaidy, Mourad Mbarki

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In this work, it have investigated the effect of electron irradiation on the output characteristics of n+/p GaAs solar cell. The studied solar cell is exposed to an electron beam with kinetic energy of 1 MeV under AM0 illumination. In this work, it have used our own software to calculate the damage caused by these energetic particles. Indeed, these particles produce severe degradation on the performances of the solar cells. The aim of this work is to investigate the effect of electronic irradiation on the J(V) characteristics upon the fluence of particles φ (electron/cm2). Thereafter, we have evaluated the degradation of its performances such as the short circuit current J_sc, the open circuit voltage V_oc the efficiency η with respect to the fluence φ of electrons. it have shown that the variation of these parameters decrease linearly with the logarithm of the fluence φ, and their degradation begins from a threshold value φ_m. To validate our calculation, we have compared our results with other theoretical and experimental results available in the literature and we have found a good agreement between them.

Keywords: solar cells, GaAs, short circuit current, open circuit voltage, fluence, degradation

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Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Satoshi Nishimura

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Although much information has been garnered from the genomes of humans and mice, it remains difficult to extend that information to explain physiological and pathological phenomena. This is because the processes underlying life are by nature stochastic and fluctuate with time. Thus, we developed novel "in vivo molecular imaging" method based on single and two-photon microscopy. We visualized and analyzed many life phenomena, including common adult diseases. We integrated the knowledge obtained, and established new models that will serve as the basis for new minimally invasive therapeutic approaches.

Keywords: two photon microscope, intravital visualization, thrombus, artery

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Mahboubeh Davoudi Pahnekolayi

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Begonia rex cv. DS-EYWA is a rare, unique cultivar of begonia rex with curly colorful leaves. Optimization of an in vitro efficient regeneration protocol by focusing on transverse Thin Cell Layer (tTCL) petiole explants for high-scale production of such a beautiful cultivar was considered as our main purpose in this experiment. Thus, various concentrations of Plant Growth Regulators (PGRs) including 6-Benzylaminopurine (BAP), Thidiazuron (TDY), and –Naphthaleneacetic Acid (NAA), were selected in a Completely Randomized Design (CRD) to establish and optimize the direct organogenesis efficiency of this cultivar. Cultivation of 1 mm tTCL petiole explants in noted treatments showed that 1.5 mgl-1 BAP + 0.5 mgl-1 NAA can induce the highest number of direct regenerated shoots and lower concentration of BAP (0.5 mgl-1) can be suggested for shoot elongation before rooting stage. Elongated shoots were successfully rooted in MS free basal medium and acclimatized in 1:1 peat moss: perlite sterilized pot mixture.

Keywords: begonia rare cultivar, direct organogenesis, explant type, regeneration, thin cell layering (TCL)

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Authors: Aysha Al Sha'aibi

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Algal blooms of the dinoflagellate species Noctiluca scintillans became frequent events in Omani waters. The current study aims at elucidating the abundance, size variation and observations on the feeding mechanism performed by this species during the winter bloom. An attempt was made, to relate observed biological parameters of the Noctiluca population to environmental factors. Field studies spanned the period from December 2014 to April 2015. Samples were collected from Bandar Rawdah (Muscat region) by Bongo nets, twice per week, from the surface and the integrated upper mixed layer. The measured environmental variables were: temperature, salinity, dissolved oxygen, chlorophyll a, turbidity, nitrite, phosphate, wind speed and rainfall. During the winter bloom (from December 2014 through February 2015), the abundance exhibited the highest concentration on 17 February (640.24×106 cell.L-1) in oblique samples and 83.9x103 cell.L-1 in surface samples, with a subsequent decline up to the end of April. The average number of food vacuoles inside Noctiluca cells was 1.5 per cell; the percentage of feeding Noctiluca compared to the entire population varied from 0.01% to 0.03%. Both the surface area of the Noctiluca symbionts (Pedinomonas noctilucae) and cell diameter were maximal in December. In oblique samples the highest average cell diameter and the surface area of symbiont algae were 751.7 µm and 179.2x103 µm2 respectively. In surface samples, highest average cell diameter and the surface area of symbionts were 760 µm and 284.05x103 µm2 respectively. No significant correlations were detected between Noctiluca’s biological parameters and environmental variables except for the correlation between cell diameter and chlorophyll a, also between symbiotic algae surface area and chlorophyll a. The high correlation of chlorophyll a was as a reason of endosymbiotic algae Pedinomonas noctilucae and green Noctiluca enhanced chlorophyll during bloom. All correlations among biological parameters were significant; they are perhaps one of major factors that mediating high growth rates, generating millions of cell per liter in a short time range. The results gained from this study will provide a beneficial background for understanding deeply the development of coastal algal blooms of Noctiluca scintillans. Moreover, results could be used in different applications related to marine environment.

Keywords: abundance, feeding activities, Noctiluca scintillans, Oman

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Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

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Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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Authors: Hye-Young Shin, Chan Kee Park

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Background: To compare the thinning patterns of the ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Methods: Twenty eyes of eleven patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5% and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5% and 1% probability level within the area corresponding to the affected VF. The 5% and 1% TAI were compared between the GCIPL and pRNFL measurements. Results: The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5% and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all P < 0.01). Conclusions: Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

Keywords: brain lesion, macular ganglion cell, inner plexiform layer, spectral-domain optical coherence tomography

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Sarim Ahmad

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The Single Cell Gel Electrophoresis Assay (SCGE, known as comet assay) is a potential, uncomplicated, sensitive and state-of-the-art technique for quantitating DNA damage at individual cell level and repair from in vivo and in vitro samples of eukaryotic cells and some prokaryotic cells, being popular in its widespread use in various areas including human biomonitoring, genotoxicology, ecological monitoring and as a tool for research into DNA damage or repair in different cell types in response to a range of DNA damaging agents, cancer risk and therapy. The method involves the encapsulation of cells in a low-melting-point agarose suspension, lysis of the cells in neutral or alkaline (pH > 13) conditions, and electrophoresis of the suspended lysed cells, resulting in structures resembling comets as observed by fluorescence microscopy; the intensity of the comet tail relative to the head reflects the number of DNA breaks. The likely basis for this is that loops containing a break lose their supercoiling and become free to extend towards the anode. This is followed by visual analysis with staining of DNA and calculating fluorescence to determine the extent of DNA damage. This can be performed by manual scoring or automatically by imaging software. The assay can, therefore, predict an individual’s tumor sensitivity to radiation and various chemotherapeutic drugs and further assess the oxidative stress within tumors and to detect the extent of DNA damage in various cancerous and precancerous lesions of oral cavity.

Keywords: comet assay, single cell gel electrophoresis, DNA damage, early detection test

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Authors: Ana Mafalda Silva, Rebeca Fontes, Ana Paula Vaz, Carla Carreira, Ana Corte-Real

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Decades of research on the topic of interpersonal violence against minors highlight five main conclusions: 1) it causes harmful effects on children's development and health; 2) it is prevalent; 3) it violates children's rights; 4) it can be prevented and 5) parents are the main aggressors. The child abuse scenario is identified through clinical observation, administrative data and self-reports. The most used instruments are self-reports; however, there are no valid and reliable self-report instruments for minors, which consist of a retrospective interpretation of the situation by the victim already in her adult phase and/or by her parents. Clinical observation and collection of information, namely from the orofacial region, are essential in the early identification of these situations. The management of medical data, such as personal data, must comply with the General Data Protection Regulation (GDPR), in Europe, and with the General Law of Data Protection (LGPD), in Brazil. This review aims to answer the question: In a situation of medical assistance to minors, in the suspicion of interpersonal violence, due to mistreatment, is it necessary for the guardians to provide consent in the registration and sharing of personal data, namely medical ones. A scoping review was carried out based on a search by the Web of Science and Pubmed search engines. Four papers and two documents from the grey literature were selected. As found, the process of identifying and signaling child abuse by the health professional, and the necessary early intervention in defense of the minor as a victim of abuse, comply with the guidelines expressed in the GDPR and LGPD. This way, the notification in maltreatment scenarios by health professionals should be a priority and there shouldn’t be the fear or anxiety of legal repercussions that stands in the way of collecting and treating the data necessary for the signaling procedure that safeguards and promotes the welfare of children living with abuse.

Keywords: child abuse, disease notifications, ethics, healthcare assistance

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Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

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Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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Authors: Naji Ali Albakay, Abdulrahman Alothaim, Isa Barshushi

Abstract:

The most common quadrature amplitude modulator (QAM) applies two Mach-Zehnder Modulators (MZM) and one phase shifter to generate high order modulation format. The bias of MZM changes over time due to temperature, vibration, and aging factors. The change in the biasing causes distortion to the generated QAM signal which leads to deterioration of bit error rate (BER) performance. Therefore, it is critical to be able to lock MZM’s Q point to the required operating point for good performance. We propose a technique for automatic bias control (ABC) of QAM transmitter using BER measurements and gradient descent optimization algorithm. The proposed technique is attractive because it uses the pertinent metric, BER, which compensates for bias drifting independently from other system variations such as laser source output power. The proposed scheme performance and its operating principles are simulated using OptiSystem simulation software for 4-QAM and 16-QAM transmitters.

Keywords: automatic bias control, optical fiber communication, optical modulation, optical devices

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Authors: Gema M. Rodado, Jose M. Olavarrieta

Abstract:

Hydrogen fuel cell technologies have experienced a great boost in the last decades, significantly increasing the production of these devices for both stationary and portable (mainly automotive) applications; these are influenced by two main factors: environmental pollution and energy shortage. A fuel cell is an electrochemical device that converts chemical energy directly into electricity by using hydrogen and oxygen gases as reactive components and obtaining water and heat as byproducts of the chemical reaction. Fuel cells, specifically those of Proton Exchange Membrane (PEM) technology, are considered an alternative to internal combustion engines, mainly because of the low emissions they produce (almost zero), high efficiency and low operating temperatures (< 373 K). The introduction and use of fuel cells in the automotive market requires the development of standardized and validated procedures to test and evaluate their performance in different environmental conditions including vibrations and freeze-thaw cycles. These situations of vibration and extremely low/high temperatures can affect the physical integrity or even the excellent operation or performance of the fuel cell stack placed in a vehicle in circulation or in different climatic conditions. The main objective of this work is the development and validation of vibration and freeze-thaw cycling test procedures for fuel cell stacks that can be used in a vehicle in order to consolidate their safety, performance, and durability. In this context, different experimental tests were carried out at the facilities of the National Hydrogen Centre (CNH2). The experimental equipment used was: A vibration platform (shaker) for vibration test analysis on fuel cells in three axes directions with different vibration profiles. A walk-in climatic chamber to test the starting, operating, and stopping behavior of fuel cells under defined extreme conditions. A test station designed and developed by the CNH2 to test and characterize PEM fuel cell stacks up to 10 kWe. A 5 kWe PEM fuel cell stack in off-operation mode was used to carry out two independent experimental procedures. On the one hand, the fuel cell was subjected to a sinusoidal vibration test on the shaker in the three axes directions. It was defined by acceleration and amplitudes in the frequency range of 7 to 200 Hz for a total of three hours in each direction. On the other hand, the climatic chamber was used to simulate freeze-thaw cycles by defining a temperature range between +313 K and -243 K with an average relative humidity of 50% and a recommended ramp up and rump down of 1 K/min. The polarization curve and gas leakage rate were determined before and after the vibration and freeze-thaw tests at the fuel cell stack test station to evaluate the robustness of the stack. The results were very similar, which indicates that the tests did not affect the fuel cell stack structure and performance. The proposed procedures were verified and can be used as an initial point to perform other tests with different fuel cells.

Keywords: climatic chamber, freeze-thaw cycles, PEM fuel cell, shaker, vibration tests

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Authors: M. Sadeghi, H. Pezeshk, R. Tusserkani, A. Sharifi Zarchi, A. Malekpour, M. Foroughmand, S. Goliaei, M. Totonchi, N. Ansari–Pour

Abstract:

The role and relative importance of intrinsic and extrinsic factors in the development of complex diseases such as cancer still remains a controversial issue. Determining the amount of variation explained by these factors needs experimental data and statistical models. These models are nevertheless based on the occurrence and accumulation of random mutational events during stem cell division, thus rendering cancer development a stochastic outcome. We demonstrate that not only individual genome sequencing is uninformative in determining cancer risk, but also assigning a unique genome sequence to any given individual (healthy or affected) is not meaningful. Current whole-genome sequencing approaches are therefore unlikely to realize the promise of personalized medicine. In conclusion, since genome sequence differs from cell to cell and changes over time, it seems that determining the risk factor of complex diseases based on genome sequence is somewhat unrealistic, and therefore, the resulting data are likely to be inherently uninformative.

Keywords: cancer risk, extrinsic factors, genome sequencing, intrinsic factors

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Authors: M. Yusuf Ansari, Asad Abbas

Abstract:

Proton exchange membrane (PEM) fuel cell is a very efficient and promising energy conversion device. Although Nafion® is considered as benchmark materials for membrane used in PEM fuel cell, it has limitations that restrict its uses. Alternative materials for the membrane is always a challenging field for researchers. Sulfonated poly(ether ether ketone) (SPEEK) is one of the promising material for membrane due to its chemical and mechanical stability and lower cost. In this work, SPEEK is synthesized, and property booster such as silica nanoparticles and polyvinyl alcohol (PVA) are also added to analyse changes in properties such as water uptake, IEC, and conductivity. It has been found that adding PVA support high water uptake and proton conductivity but at large amount of PVA reduces the proton conductivity due to very high water uptake. Adding silica enhances water uptake and proton conductivity.

Keywords: PEM Membrane, sulfonated poly (ether ether ketone) (SPEEK), silica fumes (SiO2), polyvinyl alcohol (PVA)

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Authors: Rinat Arbel-Goren, Joel Stavans

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Cell-to-cell variations in transcript or protein abundance, called noise, may give rise to phenotypic variability between isogenic cells, enhancing the probability of survival under stress conditions. These variations may be introduced by post-transcriptional regulatory processes such as non-coding, small RNAs stoichiometric degradation of target transcripts in bacteria. We study the iron homeostasis network in Escherichia coli, in which the RyhB small RNA regulates the expression of various targets as a model system. Using fluorescence reporter genes to detect protein levels and single-molecule fluorescence in situ hybridization to monitor transcripts levels in individual cells, allows us to compare noise at both transcript and protein levels. The experimental results and computer simulations show that extrinsic noise buffers through a feed-forward loop configuration the increase in variability introduced at the transcript level by iron deprivation, illuminating the important role that extrinsic noise plays during stress. Surprisingly, extrinsic noise also decouples of fluctuations of two different targets, in spite of RyhB being a common upstream factor degrading both. Thus, phenotypic variability increases under stress conditions by the decoupling of target fluctuations in the same cell rather than by increasing the noise of each. We also present preliminary results on the adaptation of cells to prolonged iron deprivation in order to shed light on the evolutionary role of post-transcriptional downregulation by small RNAs.

Keywords: cell-to-cell variability, Escherichia coli, noise, single-molecule fluorescence in situ hybridization (smFISH), transcript

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Authors: A. W. Zularisam, Sveta Thakur, Lakhveer Singh, Mimi Sakinah Abdul Munaim

Abstract:

Clostridium sp. LS2 was immobilised by entrapment in polyethylene glycol (PEG) gel beads to improve the biohydrogen production rate from palm oil mill effluent (POME). We sought to explore and optimise the hydrogen production capability of the immobilised cells by studying the conditions for cell immobilisation, including PEG concentration, cell loading and curing times, as well as the effects of temperature and K2HPO4 (500–2000 mg/L), NiCl2 (0.1–5.0 mg/L), FeCl2 (100–400 mg/L) MgSO4 (50–200 mg/L) concentrations on hydrogen production rate. The results showed that by optimising the PEG concentration (10% w/v), initial biomass (2.2 g dry weight), curing time (80 min) and temperature (37 °C), as well as the concentrations of K2HPO4 (2000 mg/L), NiCl2 (1 mg/L), FeCl2 (300 mg/L) and MgSO4 (100 mg/L), a maximum hydrogen production rate of 7.3 L/L-POME/day and a yield of 0.31 L H2/g chemical oxygen demand were obtained during continuous operation. We believe that this process may be potentially expanded for sustained and large-scale hydrogen production.

Keywords: hydrogen, polyethylene glycol, immobilised cell, fermentation, palm oil mill effluent

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Authors: Venoos Iman, Suzita Mohd Noor, Syam Mohan, Mohamad Ibrahim Noordin

Abstract:

Girinimbine, a carbazole alkaloid was isolated from the stem bark and root of Murraya koenigii and its structure and purity was identified by HPLC and LC-MS. Here we report that Girinimbine strongly inhibit angiogenesis activity both in vitro and in vivo. MTT result showed that girinimbine inhibits cell proliferation of the HUVECS cell line in vitro. Result of endothelial cell invasion, migration, tube formation and wound healing assays also demonstrated significant time and does dependent inhibition by girinimbine. Moreover, girinibine mediates its anti-angiogenic activity through up- and down-regulation of angiogenic and anti-aniogenic proteins. Furthermore, anti-angiogenic potential of girinimbine was evidenced in vivo on zebrafish model. Girinimbine inhibited neo-vessels formation in zebrafish embryos during 24 hours exposure time. Together, these results demonstrated for the first time that girinimbine could effectively suppress angiogenesis and strongly suggest that it might be a novel angiogenesis inhibitor.

Keywords: anti-angiogenic, carbazole alkaloid, girinimbine, zebrafish

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Authors: Li Yang, Yang Song, Martin Y. M. Chiang

Abstract:

Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

Procedia PDF Downloads 191