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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29792905/together-means-more-happiness-relationship-status-moderates-the-association-between-brain-structure-and-life-satisfaction
#2
Xingxing Zhu, Kangcheng Wang, Li Chen, Aihua Cao, Qunlin Chen, Junchao Li, Jiang Qiu
Life satisfaction reflects an individual's general evaluation of their overall quality of life. It has been hypothesized that relationship status (i.e. state of intimate relationship such as marriage, unmarried cohabiting, dating with others, single or divorce) may influence individual life satisfaction. However, there is little accessible empirical evidence that allows us to explore this proposition. Using a large sample of young adults (n = 1031) from the Human Connectome Project (HCP), we showed that compared to other relationship statuses (e...
May 21, 2018: Neuroscience
https://www.readbyqxmd.com/read/29792826/fast-evolving-human-specific-neural-enhancers-are-associated-with-aging-related-diseases
#3
Han Chen, Chunyan Li, Zhicheng Zhou, Han Liang
The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging-related diseases and enhancers acquired after the human-chimpanzee divergence. We report a 5-fold increased evolutionary rate of enhancers that are activated in neural tissues, leading to fixation of ∼100 human-specific enhancers potentially under adaptation...
May 23, 2018: Cell Systems
https://www.readbyqxmd.com/read/29792446/an-expanded-theory-of-alzheimer-s-caregiving
#4
Samantha F Lang, Blaine J Fowers
The ancient and cross-culturally prevalent pattern of caregiving suggests that long-term caregiving is species characteristic for humans. If so, then an evolutionary account of the adaptation(s) that underwrite this caregiving is necessary, particularly for the one-sided and long-term nature of Alzheimer's caregiving. Four standard evolutionary explanations are evaluated: kin selection theory, the grandmother hypothesis, direct reciprocity, and indirect reciprocity. Each is found inadequate to explain caregiving because of the lack of reproductive benefits...
May 24, 2018: American Psychologist
https://www.readbyqxmd.com/read/29792360/newer-human-inosine-5-monophosphate-dehydrogenase-2-himpdh2-inhibitors-as-potential-anticancer-agents
#5
Chetan P Shah, Prashant S Kharkar
Human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2), being an age-old target, has attracted attention recently for anticancer drug development. Mycophenolic acid (MPA), a well-known immunosuppressant drug, was used a lead structure to design and develop modestly potent and selective analogues. The steep structure-activity relationship (SAR) requirements of the lead molecule left little scope to synthesise newer analogues. Here, newer MPA amides were designed, synthesised and evaluated for hIMPDH2 inhibition and cellular efficacy in breast, prostate and glioblastoma cell lines...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29792337/titanium-dioxide-nanoparticles-induce-in-vitro-autophagy
#6
X Dai, R Liu, N Li, J Yi
AIM: Concerns about the possible toxicity to environment and human health of titanium dioxide nanoparticles (TiO2 NPs) are increasing. The aim of this study was to investigate the relationship between toxicology and autophage in vitro. METHODS: RAW 264.7 cells were exposed to five concentrations (50, 100, 200, 300, and 400 μg/mL) and two particle size of TiO2 NPs (30 and 100 nm) for 24 h. RESULTS: The results showed that TiO2 NPs decreased cell viability, phagocytic rate, and phagocytic index in a concentration-dependent manner, thereby inducing autophagy...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29792248/metataxonomic-analysis-of-individuals-at-bmi-extremes-and-monozygotic-twins-discordant-for-bmi
#7
Casey T Finnicum, Stieneke Doornweerd, Conor V Dolan, Justin M Luningham, Jeffrey J Beck, Gonneke Willemsen, Erik A Ehli, Dorret I Boomsma, Richard G Ijzerman, Gareth E Davies, Eco J C de Geus
OBJECTIVE: The human gut microbiota has been demonstrated to be associated with a number of host phenotypes, including obesity and a number of obesity-associated phenotypes. This study is aimed at further understanding and describing the relationship between the gut microbiota and obesity-associated measurements obtained from human participants. SUBJECTS/METHODS: Here, we utilize genetically informative study designs, including a four-corners design (extremes of genetic risk for BMI and of observed BMI; N = 50) and the BMI monozygotic (MZ) discordant twin pair design (N = 30), in order to help delineate the role of host genetics and the gut microbiota in the development of obesity...
June 2018: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://www.readbyqxmd.com/read/29792148/homopiperazine-derived-female-controlled-vaginal-trichomonacidal-contraceptive-an-addition-to-structure-activity-relationship
#8
B S Rahul, Bindu Saraswati, C Shiju, Gopal Gupta, Nand Lal
BACKGROUND: In our previous work, several piperazine derived bis(dialkylaminethiocarbonyl) disulfides and disulfide esters of dithiocarbamic acid have been synthesized and evaluated for their spermicidal and microbicidal efficacy. These studies have provided some promising compounds for developing a dually active vaginal microbicidal contraceptive which are under pre-clinical stage [1, 16, 17]. OBJECTIVE: The main objective of this study was to design, synthesis and biological evaluation of bis(dialkylaminethiocarbonyl) disulfides (4-15) and 2,2'-disulfanediylbis (3-(substituted- 1-yl) propane-2,1-diyl) disubstituted-1-carbodithioates (19-28) as non-surfactant molecules capable of eliminating Trichomonas vaginalis as as well as irreversibly immobilizing 100% human sperm promptly...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29791911/improving-translation-from-preclinical-studies-to-clinical-trials-in-acute-kidney-injury
#9
Marco Fiorentino, John A Kellum
BACKGROUND: Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. SUMMARY: Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease...
May 23, 2018: Nephron
https://www.readbyqxmd.com/read/29791590/lncrna-ccat1-promotes-cell-proliferation-migration-and-invasion-by-down-regulation-of-mir-143-in-ftc-133-thyroid-carcinoma-cell-line
#10
Tianzheng Yang, Hongyan Zhai, Ruihong Yan, Zhenhu Zhou, Lei Gao, Luqing Wang
Thyroid cancer is a common malignant tumor. Long non-coding RNA colon cancer-associated transcript 1 (lncRNA CCAT1) is highly expressed in many cancers; however, the molecular mechanism of CCAT1 in thyroid cancer remains unclear. Hence, this study aimed to investigate the effect of CCAT1 on human thyroid cancer cell line FTC-133. FTC-133 cells were transfected with CCAT1 expressing vector, CCAT1 shRNA, miR-143 mimic, and miR-143 inhibitor, respectively. After different treatments, cell viability, proliferation, migration, invasion, and apoptosis were measured...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29791298/the-influence-of-dopamine-on-cognitive-flexibility-is-mediated-by-functional-connectivity-in-young-but-not-older-adults
#11
Anne S Berry, Vyoma D Shah, William J Jagust
Dopaminergic signaling in striatum is strongly implicated in executive functions including cognitive flexibility. However, there is a paucity of multimodal research in humans defining the nature of relationships between endogenous dopamine, striatal network activity, and cognition. Here, we measured dopamine synthesis capacity in young and older adults using the PET tracer 6-[18 F]fluoro-l- m-tyrosine and examined its relationship with cognitive performance and functional connectivity during an fMRI study of task switching...
May 23, 2018: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/29791212/indian-novice-nurses-perceptions-of-their-role-in-caring-for-women-who-have-experienced-intimate-partner-violence
#12
Sailaxmi Gandhi, Vijayalakshmi Poreddi, Reddy Ss Nikhil, Marimuthu Palaniappan, Suresh Bada Math
BACKGROUND: intimate partner violence (IPV) is a significant health problem and a gross violation of the human rights of women. Nurses play an important role in providing support for these women. There is limited research on nurses' understanding and perceptions of their role in caring for women with IPV issues in India. AIM: to assess novice nurses' perceptions of self-efficacy, educational preparedness and their role in this area. METHODS: this was a cross-sectional descriptive survey carried out among a convenience sample of novice nurses (n=83) at a tertiary care centre using self-reported questionnaires...
May 24, 2018: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/29791163/on-the-relationship-between-excited-state-lifetime-and-isomerization-quantum-yield-in-animal-rhodopsins-beyond-the-one-dimensional-landau-zener-model
#13
Mohsen M T El-Tahawy, Artur Nenov, Oliver Weingart, Massimo Olivucci, Marco Garavelli
We show that the speed of the chromophore photoisomerization of animal rhodopsins is not a relevant control knob for their light sensitivity. This result is at odd with the momentum-driven tunnelling rationale (i.e., assuming a one-dimensional Landau-Zener model for the decay: Zener, C. "Non-Adiabatic Crossing of Energy Levels", Proceedings of the Royal Society of London. Series A 1932, 137 (833), 696-702) holding that a faster nuclear motion through the conical intersection translates into a higher quantum yield and, thus, light sensitivity...
May 23, 2018: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29790308/impact-of-low-level-radiation-on-concentrations-of-some-trace-elements-in-radiation-workers
#14
Nima Rostampour, Tinoosh Almasi, Masoumeh Rostampour, Hamid Reza Sadeghi, Ehsan Khodamoradi, Reyhaneh Razi, Zahra Derakhsh
Introduction: Small variations in trace element levels may cause important physiological changes in the human body. This study aims to evaluate five important trace elements in radiation workers. Method: In this study, 44 radiation workers and an equal number of non-radiation workers were selected as the case and control group, respectively. The concentrations of iron, magnesium, zinc, copper, and selenium in the serum of the participants were measured using an Atomic Absorption Spectrometry (AAS)...
May 2018: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29790300/aspiration-pneumonia-induces-muscle-atrophy-in-the-respiratory-skeletal-and-swallowing-systems
#15
Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose
BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle...
May 22, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29789903/stabilization-of-symptomatic-carotid-atherosclerotic-plaques-by-statins-a-clinico-pathological-analysis
#16
Takao Konishi, Naohiro Funayama, Tadashi Yamamoto, Daisuke Hotta, Ryota Nomura, Yusuke Nakagaki, Takeo Murahashi, Kenji Kamiyama, Tetsuyuki Yoshimoto, Takeshi Aoki, Shinya Tanaka
Human and animal studies have revealed a stabilization of atherosclerotic plaques by statins. However, the stabilization of human carotid plaques has not been thoroughly described pathologically. This analysis explored the relationship between statin therapy and plaque stability in carotid endarterectomy (CEA) specimens. We analyzed specimens harvested between May 2015 and February 2017, from 79 consecutive patients presenting with > 70% carotid artery stenoses, of whom 66 were untreated (group 1) and 13 treated (group 2) with a statin...
May 22, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29789710/is-misreporting-of-dietary-intake-by-weighed-food-records-or-24-hour-recalls-food-specific
#17
Leanne Garden, Heather Clark, Stephen Whybrow, R James Stubbs
BACKGROUND/OBJECTIVES: Healthy eating advice is informed, in part, by dietary surveys that rely on self-reported data. Misreporting of food intake may distort relationships between diet and health outcomes. This study directly quantified the food groups that were under-reported or over-reported in common dietary assessment techniques. SUBJECTS/METHODS: Food and drink consumption of 59 adults, with ad libitum access to a range of familiar foods, was objectively and covertly measured by investigators, and validated against independent measures of energy balance, while participants were resident in the Human Nutrition Unit of the Rowett Institute...
May 23, 2018: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29789652/small-hypoxia-primed-mesenchymal-stem-cells-attenuate-graft-versus-host-disease
#18
YongHwan Kim, Hye Jin Jin, Jinbeom Heo, Hyein Ju, Hye-Yeon Lee, Sujin Kim, Seungun Lee, Jisun Lim, Sang Young Jeong, JiHye Kwon, Miyeon Kim, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Hyun Ho Hwang, Hwan Yeul Yu, Chae-Min Ryu, Hong Bae Jeon, Dong-Myung Shin
Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation...
May 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29789527/regulator-of-chromatin-condensation-1-abrogates-the-g1-cell-cycle-checkpoint-via-cdk1-in-human-papillomavirus-e7-expressing-epithelium-and-cervical-cancer-cells
#19
Lijun Qiao, Jingyi Zheng, Yonghao Tian, Qishu Zhang, Xiao Wang, Jason J Chen, Weifang Zhang
Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase and plays key roles in nucleo-cytoplasmic transport, mitosis, and nuclear envelope assembly. RCC1 is known to be a critical cell cycle regulator whose loss causes G1 phase arrest, but the molecular basis for this regulation is poorly understood. Furthermore, little is known about the relationship between RCC1 and carcinomas. Human papillomavirus (HPV) infection is highly associated with the development of cervical cancer...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789489/reconciling-the-entomological-hazard-and-disease-risk-in-the-lyme-disease-system
#20
Max McClure, Maria Diuk-Wasser
Lyme disease (LD) is a commonly cited model for the link between habitat loss and/or fragmentation and disease emergence, based in part on studies showing that forest patch size is negatively related to LD entomological risk. An equivalent relationship has not, however, been shown between patch size and LD incidence (LDI). Because entomological risk is measured at the patch scale, while LDI is generally assessed in relation to aggregate landscape statistics such as forest cover, we posit that the contribution of individual patches to human LD risk has not yet been directly evaluated...
May 22, 2018: International Journal of Environmental Research and Public Health
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