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Cell mechanics

Danielle Oliveira Dos Anjos, Eliomara Sousa Sobral Alves, Vinicius Tomaz Gonçalves, Sheila Suarez Fontes, Mateus Lima Nogueira, Ana Márcia Suarez-Fontes, João Batista Neves da Costa, Fabricio Rios-Santos, Marcos André Vannier-Santos
Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β-lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β-lapachone derivative affected the T...
October 12, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Priya Mishra, Updesh Dixit, Ashutosh K Pandey, Alok Upadhyay, Virendra N Pandey
We recently identified a cell-factor, ErbB3 binding protein 1 (Ebp-1), which specifically interacts with the viral RNA genome and modulates HCV replication and translation. Ebp1 has two isoforms, p48, and p42, that result from differential splicing. We found that both isoforms interact with HCV proteins NS5A and NS5B, as well as cell-factor PKR. The p48 isoform, which localizes in the cytoplasm and nuclei, promoted HCV replication, whereas the shorter p42 isoform, which resides exclusively in the cytoplasm, strongly inhibited HCV replication...
October 19, 2016: Virology
Bryan A Johnson, Heather L Aloor, Cary A Moody
Human papillomaviruses (HPV) exhibit constitutive activation of ATM and ATR DNA damage response (DDR) pathways, which are required for productive viral replication. Expression of HPV31 E7 alone is sufficient to activate the DDR through an unknown mechanism. Here, we demonstrate that the E7 Rb binding domain is required to increase levels of many DDR proteins, including ATM, Chk2, Chk1, the MRN components MRE11, Rad50, and NBS1, as well as the homologous recombination repair proteins BRCA1 and Rad51. Interestingly, we have found that the increase in these DNA repair proteins does not occur solely at the level of transcription, but that E7 broadly increases the half-life of these DDR factors, a phenotype that is lost in the E7 Rb binding mutant...
October 19, 2016: Virology
Yan Xu, Yawei Xing, Yanjie Xu, Chahua Huang, Huihui Bao, Kui Hong, Xiaoshu Cheng
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis...
October 17, 2016: Environmental Toxicology and Pharmacology
Ki Mo Kim, Deok Rim Heo, Young-A Kim, Jun Lee, No Soo Kim, Ok-Sun Bang
Coniferaldehyde (CA) exerts anti-inflammatory properties by inducing heme oxygenase-1 (HO-1). To define the regulation mechanism by which CA induces a cytoprotective function and HO-1 expression, the up-stream regulations involved in the activation of nuclear transcription factor-erythroid 2-related factor (Nrf)-2/HO-1 pathway were investigated. CA dramatically increased the Nrf-2 nuclear translocation and HO-1 expression. Lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and cell death were down-regulated by CA, which were reversed by inhibition of HO-1 activity...
October 17, 2016: Environmental Toxicology and Pharmacology
Sunil Nath
As the chief energy source of eukaryotic cells, it is important to determine the thermodynamic efficiency of ATP synthesis in oxidative phosphorylation (OX PHOS). Previous estimates of the thermodynamic efficiency of this vital process have ranged from Lehninger's original back-of-the-envelope calculation of 38% to the often quoted value of 55-60% in current textbooks of biochemistry, to high values of 90% from recent information theoretic considerations, and reports of realizations of close to ideal 100% efficiencies by single molecule experiments...
October 15, 2016: Biophysical Chemistry
Marilucia Santos Ludovico, Luciano Moura Martins, Juares Ednaldo Romero Bianco, Célia Guadalupe Tardelli de Jesus Andrade, Rosabel Falcon, Paulo Pinto Joazeiro, Maria Silvia Viccari Gatti, Tomomasa Yano
Plesiomonas shigelloides isolated from water in Brazil was previously described as a hemorrhagic heat-labile cytotoxic-enterotoxin producer. We purified this toxin from culture supernatants using ion metallic affinity chromatography (IMAC) followed by molecular exclusion chromatography. The pure toxin presented molecular mass of 50kDa and isoelectric point (pI) around 6.9 by 2D electrophoresis. When injected intravenously, the purified cytotoxic-enterotoxin induced also severe spasms followed by sudden death of mice...
October 19, 2016: Brazilian Journal of Infectious Diseases
Yun Bai, Jia Wang, Jing Han, Xiao-Li Xie, Cheng-Guang Ji, Jie Yin, Lei Chen, Cun-Kai Wang, Xiao-Yu Jiang, Wei Qi, Hui-Qing Jiang
BACKGROUND AND AIMS: BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. METHODS: BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice...
October 22, 2016: Molecular Carcinogenesis
Muhammad Imran Rahim, Andreas Weizbauer, Florian Evertz, Andrea Hoffmann, Manfred Rohde, Birgit Glasmacher, Henning Windhagen, Gerhard Gross, Jan-Marten Seitz, Peter P Mueller
Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels...
October 22, 2016: Journal of Biomedical Materials Research. Part A
Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
Joanna Pancewicz-Wojtkiewicz
Lung cancer is the most common reason of cancer deaths and about 85% of these are non-small-cell lung cancer. Currently, lung cancer therapy is mainly based on the tumor node metastasis (TNM) disease staging and tumor histological classification. Despite therapeutic innovations, the prognosis for lung cancer patients has not significantly changed in the last years. Therefore, a proper understanding of cell signaling pathways involved in cancer pathogenesis seems to be essential for improvement in cancer therapy field...
October 21, 2016: Cancer Medicine
Majid Zaki Dizaji, Seyed H Ghaffari, Elham Hosseini, Nasrin Alizadeh, Shahrbano Rostami, Majid Momeny, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
AIM: Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). METHODS: Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy...
October 22, 2016: Asia-Pacific Journal of Clinical Oncology
Simone A A Romariz, Daisyléa S Paiva, Layla T Galindo, Gabriela F Barnabé, Vivian A Guedes, Cesario V Borlongan, Beatriz M Longo
AIMS: Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells...
October 21, 2016: CNS Neuroscience & Therapeutics
Silvania da Silva Teixeira, Carly Filgueira, Douglas H Sieglaff, Cindy Benod, Rosa Villagomez, Laurie J Minze, Aijun Zhang, Paul Webb, Maria Tereza Nunes
AIM: Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5-T2) exerts T3-like effects on energy consumption and lipid metabolism. 3,5-T2 also improves glucose tolerance in rats and 3,5-T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5-T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5-T2 and another form of T2 (3,3-T2) in a mouse model of diet induced obesity and determined effects of T3 and 3,5-T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose...
October 22, 2016: Acta Physiologica
Juri Bergmann, Miryam Müller, Niklas Baumann, Manuel Reichert, Carola Heneweer, Julia Bolik, Karsten Lücke, Sabine Gruber, Antonella Carambia, Susanne Boretius, Ivo Leuschner, Thomas Becker, Björn Rabe, Johannes Herkel, F Thomas Wunderlich, Hans-Willi Mitrücker, Stefan Rose-John, Dirk Schmidt-Arras
: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine interleukin 6 (IL-6) is a critical mediator of HCC development. It can signal through two distinct pathways, the IL-6 classic and the IL-6 trans-signaling pathway. While IL-6 classic signaling is important for innate and acquired immunity, IL-6 trans-signaling has been linked to accelerated liver regeneration and several chronic inflammatory pathologies. However, its implication in liver tumorigenesis has not been addressed yet...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Man Liu, Jingying Zhou, Zhiwei Chen, Alfred Sze-Lok Cheng
The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence underscores the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ("epimutations"), there is also growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells toward an immunosuppressive state...
October 22, 2016: Journal of Pathology
Zhen Lei, Abdul Sami Shaikh, Wenshuai Zheng, Xiao Yu, Jingui Yu, Jingxin Li
Itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. However, the molecular mechanisms of itch are unclear. Acid sensing ion channel 3 (ASIC3) is a sensor of acidic and primary inflammatory pain. The whole-cell patch-clamp technique was used to determine the effect of Chloroquine (CQ)on ASICs currents in primary sensory neurons or the Chinese hamster ovary (CHO) cells transfected with rat-ASIC1a or- ASIC3. Site-directed mutagenesis of plasmid was performed...
October 22, 2016: Journal of Neurochemistry
X-N Ma, C-X Ma, W-G Shi, J Zhou, H-P Ma, Y-H Gao, C J Xian, K-M Chen
OBJECTIVE: Icaritin, one effective metabolite of Herba Epimedii-derived flavonoid icariin, has a strong osteogenic activity. However, its action mechanism remains unclear. Since primary cilia have been shown to play a pivotal role in regulating the osteogenesis, we hypothesized primary cilia are indispensable in mediating icaritin osteogenic effect. MATERIALS AND METHODS: Primary rat calvarial osteoblasts were transfected with siRNA1 targeting intraflagellar transport protein 88 (IFT88), a protein required for ciliogenesis, to prevent formation of primary cilium and were treated with 10(-6) M icaritin...
October 21, 2016: Journal of Endocrinological Investigation
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