Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Reactive Oxygen and Nitrogen Species in Defense/Stress Responses Activated by Chitosan in Sycamore Cultured Cells

Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H₂O₂ and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation.     

An experimental approach towards increasing mechanical durability of extruded fish feed in the drying process

Mechanical durability of extruded fish feed must be optimized to lower economic losses as well as emission of organic matter to aquatic environments. The glass transition hypothesis for viscoelastic biopolymers is demonstrated and confirmed experimentally to be valid for extruded fish feed pellets. It is proposed and demonstrated that it is important to avoid early glass transition onset, to optimize the obtained mechanical durability. From the proposed glass transition hypothesis, immediate process relevance to the pre-drying transport mechanism is demonstrated. Furthermore, measured mechanical durability is found to range from 1.5 to 5.0% loss, for different combinations of drying parameters.     

Phenolic Phytoalexins in Rice: Biological Functions and Biosynthesis

Phytoalexins are inducible secondary metabolites possessing antimicrobial activity against phytopathogens. Rice produces a wide array of phytoalexins in response to pathogen attacks and environmental stresses. With few exceptions, most phytoalexins identified in rice are diterpenoid compounds. Until very recently, flavonoid sakuranetin was the only known phenolic phytoalexin in rice. However, recent studies have shown that phenylamides are involved in defense against pathogen attacks in rice. Phenylamides are amine-conjugated phenolic acids that are induced by pathogen infections and abiotic stresses including ultra violet (UV) radiation in rice. Stress-induced phenylamides, such as N-trans-cinnamoyltryptamine, N-p-coumaroylserotonin and N-cinnamoyltyramine, have been reported to possess antimicrobial activities against rice bacterial and fungal pathogens, an indication of their direct inhibitory roles against invading pathogens. This finding suggests that phenylamides act as phytoalexins in rice and belong to phenolic phytoalexins along with sakuranetin. Phenylamides also have been implicated in cell wall reinforcement for disease resistance and allelopathy of rice. Synthesis of phenolic phytoalexins is stimulated by phytopathogen attacks and abiotic challenges including UV radiation. Accumulating evidence has demonstrated that biosynthetic pathways including the shikimate, phenylpropanoid and arylmonoamine pathways are coordinately activated for phenolic phytoalexin synthesis, and related genes are induced by biotic and abiotic stresses in rice.     

大口径光学元件装夹转运结构设计及分析

为了实现大口径光学元件的安全装夹、转运,通过光学元件开槽与不开槽两种装夹方式的分析,得出开槽夹紧转运方式将带来微裂纹、应力集中、成本高等缺陷,提出了利用摩擦力克服光学零件的重力和惯性力的低应力装夹转运方案。通过对光学元件低应力夹紧结构设计,并利用有限元分析方法,得到不开槽装夹方式下,光学元件的最大主应力为1.11 MPa,最大切应力为0.73 MPa,远低于光学元件破坏的强度极限,且受力均匀,无应力集中现象。     

Viscoelastic Behavior of Synthesized Liquid Soaps and Surface Activity Properties of Surfactants

In the present work, a rheological study of liquid soaps prepared from different mixture of surfactants as a function of surfactant type and concentration was performed. The curves of shear stress vs. shear rate and viscosity vs. shear rate were recorded at constant temperature, 294 ± 0.1 K. The surface activity properties were also studied. The results of the study showed that values of surface tension, γ, were in the range 31–40 mN m⁻¹ and the critical micelle concentration (CMC), was of the order 10⁻⁴ mol L⁻¹. The calculated maximum surface excess, Γ_max, varied from 2.40 to 3.66 μmol m⁻², while minimum area per molecule, A_min, varied from 41.1 (for amphoterics) to 81.4 Ų (for nonionic surfactants). The standard free energy of micellization, −29.8 and −29.3 kJ mol⁻¹ for anionic and amphoteric surfactants, respectively, were while values for nonionic surfactants varied between −31.8 and − 30.3 kJ mol⁻¹. The free energy of adsorption, was the lowest for amphoteric surfactants (−37.9 kJ mol⁻¹), followed by anionics (−40.4 kJ mol⁻¹) and nonionics (−43.34 to −46.84 kJ mol⁻¹), indicating that micellization process is spontaneous in the examined medium. The synthetized liquid soaps show pseudoplastic behavior and they achieved pipe flow. The results of this research indicate that flow behavior was affected significantly by the ionic charge of the surfactant and the ionic strength of the formulation, suggesting that the flow behavior could be changed by manipulating the choice of the surfactant and salinity. The pH value of all liquid soaps examined were weakly acidic, in the range of 5.0–6.4.     

Stress distribution in thick-walled cylinder due to non-uniform radial pressure on the example of reinforcement corrosion in concrete

This paper presents an analytical solution to the non-uniform pressure on thick-walled cylinder. The formulation is based on the linear elasticity theory (plain strain) and stress function method. As an example, the proposed solution is used to model the stress distribution due to non-uniform steel reinforcement corrosion in concrete. The model is formulated considering different scenarios of corrosion pressure distribution. It is validated against the finite element model for different cases of non-uniform pressure distributions. The results show that the corrosion-induced cracks are likely to start just beyond the anodic zone. This is confirmed by the experimental tests on concrete cylinder exposed to non-uniform accelerated corrosion of steel reinforcement. The model can be effectively used to calculate the distribution of corrosion-induced stresses in concrete.