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Chemical pathology

Murat Bozdag, Abdulmalik Saleh Alfawaz Altamimi, Daniela Vullo, Claudiu T Supuran, Fabrizio Carta
The current review is intended to highlight recent advances in the search of new and effective modulators of the metalloenzymes Carbonic Anhydrases (CAs, EC expressed in (h) humans. CAs reversibly catalyze the CO2 hydration reaction, which is of crucial importance in the regulation of a plethora of fundamental processes at cellular level as well as in complex organisms. The first section of this review will be dedicated to compounds acting as activators of the hCAs (CAAs) and their promising effects on central nervous system affecting pathologies mainly characterized from memory and learning impairments...
June 22, 2018: Current Medicinal Chemistry
Raghu Patil Junjappa, Prakash Patil, Kashi Raj Bhattarai, Hyung-Ryong Kim, Han-Jung Chae
Inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) is the most prominent and evolutionarily conserved endoplasmic reticulum (ER) membrane protein. This transduces the signal of misfolded protein accumulation in the ER, named as ER stress, to the nucleus as "unfolded protein response (UPR)." The ER stress-mediated IRE1α signaling pathway arbitrates the yin and yang of cell life. IRE1α has been implicated in several physiological as well as pathological conditions, including immune disorders...
2018: Frontiers in Immunology
Raya Sorkin, Giulia Bergamaschi, Douwe Kamsma, Guy Brand, Elya Dekel, Yifat Ofir-Birin, Ariel Rudik, Marta Gironella, Felix Ritort, Neta Regev-Rudzki, Wouter Roos, Gijs J L Wuite
A large number of studies demonstrate that cell mechanics and pathology are intimately linked. In particular, Red Blood Cell (RBC) deformability is key to their function, and is dramatically altered in the time course of diseases such as anemia and malaria. Due to the physiological importance of cell mechanics, many methods for cell mechanical probing have been developed. While single cell methods provide very valuable information, they are often technically challenging and lack high data throughput needed to distinguish differences in heterogeneous populations, while fluid flow high throughput methods miss the accuracy to detect subtle differences...
June 21, 2018: Molecular Biology of the Cell
Hong-Xuan Feng, Chun-Pu Li, Shuang-Jie Shu, Hong Liu, Hai-Yan Zhang
There is an urgent need to develop effective therapies for ischemic stroke, but the complicated pathological processes after ischemia make doing so difficult. In the current study, we identified a novel diaryl acylhydrazone derivative, A11, which has multiple neuroprotective properties in ischemic stroke models. First, A11 was demonstrated to induce neuroprotection against ischemic injury in a dose-dependent manner (from 0.3 to 3 μM) in three in vitro experimental ischemic stroke models: oxygen glucose deprivation (OGD), hydrogen peroxide, and glutamate-stimulated neuronal cell injury models...
June 20, 2018: Acta Pharmacologica Sinica
M Z Yang, T Y Zhang, H J Li, T T Yang, Z J Ding, Q Liu
Postmortem interval (PMI) estimation is one of the most challenging problems in the field of forensic science. Vitreous humor is a hotspot which has been used for PMI estimation and postmortem chemical analysis in forensic pathology. In order to provide novel perspectives for the future research of PMI estimation using vitreous humor, the comparison between vitreous humor with other common body fluids, the effect of temperature on vitreous humor, vitreous humor detection method and data fitting method have been reviewed in this paper...
April 2018: Fa Yi Xue za Zhi
Rachel E Ellsworth, Paul J Kostyniak, Lai-Har Chi, Craig D Shriver, Nicholas S Costantino, Darrell L Ellsworth
Agricultural pesticides are abundant environmental contaminants worldwide, prompting interest in studying their possible detrimental health effects. We examined organochlorine residues by quadrant (n = 245) in breast adipose tissues from 51 women with various stages of breast health to determine patterns of bioaccumulation within the breast and to assess relationships with patient clinical characteristics. Three organochlorine residues-2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and mirex-assayed by high resolution gas chromatography were abundant in breast tissue...
June 19, 2018: Environmental Toxicology
Wenjuan Yang, Keyan Zhou, Yue Zhou, Yuqian An, Tingting Hu, Jing Lu, Shichao Huang, Gang Pei
Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity. In this study, we demonstrated that naringin dihydrochalcone (NDC), a widely used dietary sweetener with strong antioxidant activity, improved the cognitive function of transgenic AD mice...
2018: Frontiers in Aging Neuroscience
Robert J Long, Reese A Charles
BACKGROUND: Otitis externa secondary to irritant or chemical exposure is well documented; however, specifically secondary to jet fuel exposure and its associated toxicology is not. Over 2 million military and civilian personnel per year are occupationally exposed to aviation fuels. CASE REPORT: An aircraft maintainer presented with noninfectious acute otitis externa secondary to external ear canal exposure to JP-5 jet fuel. Proper exposure guidelines were followed, but it was not realized that the external ear canal was involved...
July 1, 2018: Aerospace Medicine and Human Performance
Laila Eljaja, Ole J Bjerrum, Per Hartvig Honoré, Bjarke Abrahamsen
Glutamate is the major excitatory amino acid in the mammalian CNS and is involved in transmission of pain together with processes for cognition, memory and learning. In order to terminate glutamatergic neurotransmission and avoid excitotoxic damage, a balanced glutamate homeostasis is of critical importance. The level of glutamate in the synaptic cleft is regulated through the action of five subtypes of excitatory amino acid transporters (EAAT1-5). Ceftriaxone, a β-lactam, induces EAAT-2 and has proven effect for the treatment of neuropathic pain...
December 29, 2017: Scandinavian Journal of Pain
Oscar Jara, Peter J Minogue, Viviana M Berthoud, Eric C Beyer
Mouse Cx50D47A and human Cx50D47N are non-functional connexin mutants that cause dominantly-inherited cataracts. In tissue culture expression experiments, they both exhibit impaired cellular trafficking and gap junction plaque formation. Lenses of mice expressing Cx50D47A have cataracts, reduced size, drastically decreased levels of connexin50, and less severely reduced levels of connexin46. The PERK-dependent pathway of the ER response to misfolded proteins is activated, and they have impaired differentiation with retained cellular organelles...
June 15, 2018: Experimental Eye Research
Flavia F Bloise, Thamires S Oliveira, Aline Cordeiro, Tania M Ortiga-Carvalho
Skeletal muscle maintains posture and enables movement by converting chemical energy into mechanical energy, further contributing to basal energy metabolism. Thyroid hormones (thyroxine, or T4, and triiodothyronine, or T3) participate in contractile function, metabolic processes, myogenesis and regeneration of skeletal muscle. T3 classically modulates gene expression after binding to thyroid hormone nuclear receptors. Thyroid hormone effects depend on nuclear receptor occupancy, which is directly related to intracellular T3 levels...
2018: Frontiers in Physiology
V Davydenko, I Starchenko, А Davydenko, V Trufanova, V Kuznetsov
The analysis of publications shows that diverse multiple factors can induce changes in taste sensitivity and the main irritants are the chemicals of different types. However, the study of the effect of the components of dental structural materials on the state of lingual mucosa, in particular, taste sensors, has not been fully elucidated to date. The purpose of the paper was the study of the effect of monomer of the "Ftoraks" base acrylic resin on the state of the rats' lingual mucosa within 2-4 weeks after its impact...
May 2018: Georgian Medical News
Yuru Vernon Shih, Shyni Varghese
Recent advances in materials development and tissue engineering has resulted in a substantial number of bioinspired materials that recapitulate cardinal features of bone extracellular matrix (ECM) such as dynamic inorganic and organic environment(s), hierarchical organization, and topographical features. Bone mimicking materials, as defined by its self-explanatory term, are developed based on the current understandings of the natural bone ECM during development, remodeling, and fracture repair. Compared to conventional plastic cultures, biomaterials that resemble some aspects of the native environment could elicit a more natural molecular and cellular response relevant to the bone tissue...
June 6, 2018: Biomaterials
Erwin Krikken, Vitaliy Khlebnikov, Moritz Zaiss, Rajni A Jibodh, Paul J van Diest, Peter R Luijten, Dennis W J Klomp, Hanneke W M van Laarhoven, Jannie P Wijnen
BACKGROUND: The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7 T. METHODS: CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest...
June 14, 2018: Breast Cancer Research: BCR
Jing Liu, Zheng Han, Guoli Chen, Yuguo Li, Jia Zhang, Jiadi Xu, Peter C M van Zijl, Shuixing Zhang, Guanshu Liu
Sepsis-induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)-induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i...
June 13, 2018: NMR in Biomedicine
Leyi Zheng, Si Chen, Yan Cao, Liang Zhao, Yue Gao, Xuan Ding, Xiaoyu Wang, Yanqiu Gu, Shaozhan Wang, Zhenyu Zhu, Yongfang Yuan, Xiaofei Chen, Yifeng Chai
Prostate cancer (PCa) is a common and fatal cancer for men and effective treatment options are still not enough for patients. Radix et Rhizoma Rhei had been applied to treat PCa long-termly and effectively when combined with surgical treatment and chemotherapy. However, its active components and target proteins are still not quite clear. As membrane receptors play a vital role in PCa, in this study, a novel strategy that combines comprehensive 2D 3-aminopropyltriethoxysilane-decorated prostate cancer cell (DU145) membrane chromatographic (CMC) system with network pharmacology approach was developed to characterize membrane binding active components proteins from Radix et Rhizoma Rhei and their targets...
June 6, 2018: Journal of Chromatography. A
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth...
June 8, 2018: International Immunopharmacology
Alan Campion, Kenneth J Smith, Alexey V Fedulov, David Gregory, Yuwei Fan, John J Godleski
The precise identification of foreign particles in tissue for patient care and research has been studied using polarized light microscopy, electron microscopy with X-ray analysis, and electron diffraction. The goal of this study was to unambiguously identify particles in tissues using a combina-tion of polarized light microscopy and Raman microscopy, which provides chemical composition and microstructural characterization of complex materials with submicron spatial resolution. We designed a model system of stained and unstained cells that contained birefringent talc particles, and systematically investigated the influence of slide and coverslip materials, laser wavelengths, and mounting media on the Raman spectra ob-tained...
June 12, 2018: Analytical Chemistry
Georg Meisl, Thomas C T Michaels, Sara Linse, Tuomas P J Knowles
The formation of amyloid fibrils is a central phenomenon in the progressive pathology of many neurodegenerative diseases, as well as in the fabrication of functional materials. Several different molecular processes acting in concert are responsible for the formation of amyloid fibrils from monomeric protein in solution. Here, we describe a method to determine which microscopic processes drive the overall formation of fibrils by using chemical kinetics in combination with systematic experimental datasets analysed in a global manner...
2018: Methods in Molecular Biology
Chengjian Wang, Shan Qiang, Wanjun Jin, Xuezheng Song, Ying Zhang, Linjuan Huang, Zhongfu Wang
Glycoproteins play pivotal roles in a series of biological processes and their glycosylation patterns need to be structurally and functionally characterized. However, the lack of versatile methods to release N-glycans as functionalized forms has been undermining glycomics studies. Here a novel method is developed for dissociation of N-linked glycans from glycoproteins for analysis by MS and online LC/MS. This new method employs aqueous ammonia solution containing NaBH3 CN as the reaction medium to release glycans from glycoproteins as 1-amino-alditol forms...
June 6, 2018: Journal of Proteomics
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