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https://www.readbyqxmd.com/read/28437753/p-gp-modulatory-acetyl-11-keto-%C3%AE-boswellic-acid-based-nanoemulsified-carrier-system-for-augmented-oral-chemotherapy-of-docetaxel
#1
Gitu Pandey, Naresh Mittapelly, Guru Raghavendra Valicherla, Ravi Prakash Shukla, Shweta Sharma, Venkatesh Teja Banala, Sandeep Urandur, Arun Kumar Jajoriya, Kalyan Mitra, D P Mishra, J R Gayen, P R Mishra
In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery...
April 15, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28436392/the-dna-damage-response-in-neurons-die-by-apoptosis-or-survive-in-a-senescence-like-state
#2
Edward Fielder, Thomas von Zglinicki, Diana Jurk
Neurons are exposed to high levels of DNA damage from both physiological and pathological sources. Neurons are post-mitotic and their loss cannot be easily recovered from; to cope with DNA damage a complex pathway called the DNA damage response (DDR) has evolved. This recognizes the damage, and through kinases such as ataxia-telangiectasia mutated (ATM) recruits and activates downstream factors that mediate either apoptosis or survival. This choice between these opposing outcomes integrates many inputs primarily through a number of key cross-road proteins, including ATM, p53, and p21...
April 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28436298/adenocarcinoma-of-the-appendix-occurring-in-a-patient-treated-with-paclitaxel-for-locally-advanced-esophageal-cancer
#3
Constantin A Dasanu, David M Hyams, Frank J Senatore
Paclitaxel has been linked with a number of immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells and monocytes, which may in turn lead to defective T-cell activation. In addition, this agent was shown to cause mitotic arrest resembling high-grade dysplasia throughout the gastrointestinal tract, including the appendix. We have previously documented a series of lung cancer patients who developed pre-malignant colonic polyps and/or colon cancer either during or weeks following chemotherapy with paclitaxel, suggesting a potential role of this agent in their pathogenesis...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28436127/tip110-deletion-impaired-embryonic-and-stem-cell-development-involving-down-regulation-of-stem-cell-factors-nanog-oct4-and-sox2
#4
Amanda Whitmill, Ying Liu, Khalid Amine Timani, Yinghua Niu, Johnny J He
HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110(-/-) ) died post-implantation, and Tip110(-/-) embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110(-/-) embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28435247/delivery-of-curcumin-by-directed-self-assembled-micelles-enhances-therapeutic-treatment-of-non-small-cell-lung-cancer
#5
Wen-Ting Zhu, Sheng-Yao Liu, Lei Wu, Hua-Li Xu, Jun Wang, Guo-Xin Ni, Qing-Bing Zeng
BACKGROUND: It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. MATERIALS AND METHODS: In this study, CUR-loaded methoxy polyethylene glycol-polylactide (CUR/mPEG-PLA) polymeric micelles were prepared by a thin-film hydration method...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28435183/a-factor-analytic-model-of-drug-related-behavior-in-adolescence-and-its-impact-on-arrests-at-multiple-stages-of-the-life-course
#6
Matthew D Phillips
OBJECTIVES: Recognizing the inherent variability of drug-related behaviors, this study develops an empirically-driven and holistic model of drug-related behavior during adolescence using factor analysis to simultaneously model multiple drug behaviors. METHODS: The factor analytic model uncovers latent dimensions of drug-related behaviors, rather than patterns of individuals. These latent dimensions are treated as empirical typologies which are then used to predict an individual's number of arrests accrued at multiple phases of the life course...
March 2017: Journal of Quantitative Criminology
https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#7
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28433375/mosaicism-between-trophectoderm-and-inner-cell-mass
#8
REVIEW
Antonio Capalbo, Laura Rienzi
Defining the actual incidence and prevalence of mosaicism in human blastocysts still remains a difficult task. The small amount of evidence generated by animal and human studies does not support the existence of mechanisms involved in developmental arrest, clonal depletion, or aneuploidy rescue for abnormal cells in euploid/aneuploid embryos during preimplantation development. However, studies in humans are mainly descriptive and lack functional evidence. Understanding the biological mechanisms that beset preimplantation differentiation holds the potential to reveal the role of aneuploidies and gene dosage imbalances in cell fate decision, providing important clues on the origin and evolution of embryonic mosaicism...
April 19, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28432554/epigallocatechin-gallate-protects-beas-2b-cells-from-lipopolysaccharide-induced-apoptosis-through-upregulation-of-gastrin-releasing-peptide
#9
Peethambaran Divya, Bijesh Puthusseri, Denny Joseph Kollareth Manual, Mohammed Azharuddin Savanur
Gastrin-releasing peptide (GRP) plays a major role in the development and maintenance of lung epithelial cells by promoting cell division, whereas its suppression causes growth arrest and apoptosis. The present study shows that human bronchial epithelial BEAS-2B cells challenged with lipopolysaccharide (LPS), an endotoxin from gram-negative bacteria, downregulated GRP expression and induced apoptosis via upregulation of p53 and active caspase-3, signifying the importance of GRP in lung epithelial cell survival...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28432293/quiescence-of-adult-oligodendrocyte-precursor-cells-requires%C3%A2-thyroid-hormone-and-hypoxia-to-activate-runx1
#10
Yasuhito Tokumoto, Shinpei Tamaki, Yasuaki Kabe, Keiyo Takubo, Makoto Suematsu
The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432106/prohibitin-induced-obesity-leads-to-anovulation-and-polycystic-ovary-in-mice
#11
Sudharsana Rao Ande, Khanh Hoa Nguyen, Yang Xin Zi Xu, Suresh Mishra
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the most common cause of female infertility. However, the etiology of the disease and the mechanisms by which this disorder progress remain unclear. Here we report that a transgenic obese mouse (Mito-Ob) developed by overexpressing prohibitin in adipocytes develops polycystic ovaries. Initially, the female Mito-Ob mice were equally fertile to their wild-type littermates. Mito-Ob mice begin to gain weight after puberty, become significantly obese between 3-6 months of age, and roughly 25% of them become infertile by 9 months of age...
April 21, 2017: Biology Open
https://www.readbyqxmd.com/read/28431398/decreased-calpain-activity-in-chronic-myeloid-leukemia-impairs-apoptosis-by-increasing-survivin-in-myeloid-progenitors-and-xiap1-in-differentiating-granulocytes
#12
Weiqi Huang, Ling Bei, Elizabeth E Hjort, Elizabeth A Eklund
Chronic Myeloid Leukemia (CML) is characterized by translocations between chromosomes 9 and 22, resulting in expression of Bcr-abl oncogenes. Although the clinical course of CML was revolutionized by development of Bcr-abl-directed tyrosine kinase inhibitors (TKIs), CML is not cured by these agents. Specifically, the majority of subjects relapsed in clinical trials attempting TKI discontinuation, suggesting persistence of leukemia stem cells (LSCs) even in molecular remission. Identifying mechanisms of CML-LSC persistence may suggest rationale therapeutic targets to augment TKI efficacy and lead to cure...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431339/novel-coumarin-and-quinolinone-based-polycycles-as-cell-division-cycle-25-a-and-c-phosphatases-inhibitors-induce-proliferation-arrest-and-apoptosis-in-cancer-cells
#13
Clemens Zwergel, Brigitte Czepukojc, Emilie Evain-Bana, Zhanjie Xu, Giulia Stazi, Mattia Mori, Alexandros Patsilinakos, Antonello Mai, Bruno Botta, Rino Ragno, Denise Bagrel, Gilbert Kirsch, Peter Meiser, Claus Jacob, Mathias Montenarh, Sergio Valente
Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell cycle processes and are found overexpressed in a large panel of cancer typology. Here, we describe the development of two novel quinone-polycycle series of CDC25A and C inhibitors on the one hand 1a-k, coumarin-based, and on the other 2a-g, quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and at single-digit micro molar concentrations, respectively. When tested in six different cancer cell lines, compound 2c displayed the highest efficacy to arrest cell viability, showing in almost all cell lines sub-micro molar IC50 values, a profile even better than the reference compound NCS95397...
April 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431088/stationary-phase-genes-upregulated-by-polyamines-are-responsible-for-the-formation-of-escherichia-coli-persister-cells-tolerant-to-netilmicin
#14
Alexander G Tkachenko, Natalya M Kashevarova, Elena A Tyuleneva, Mikhail S Shumkov
Persisters are rare phenotypic variants of regular bacterial cells that survive lethal antibiotics or stresses owing to slowing down of their metabolism. Recently, we have shown that polyamine putrescine can upregulate persister cell formation in Escherichia coli via the stimulation of rpoS expression, encoding a master regulator of general stress response. We hypothesized that rmf and yqjD, the stationary-phase genes responsible for ribosome inactivation, might be good candidates for the similar role owing to their involvement in translational arrest and the ability to be affected by polyamines...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28430068/caring-for-patients-or-organs-new-therapies-raise-new-dilemmas-in-the-emergency-department
#15
Arjun Prabhu, Lisa S Parker, Michael A DeVita
Two potentially lifesaving protocols, emergency preservation and resuscitation (EPR) and uncontrolled donation after circulatory determination of death (uDCDD), currently implemented in some U.S. emergency departments (EDs), have similar eligibility criteria and initial technical procedures, but critically different goals. Both follow unsuccessful cardiopulmonary resuscitation and induce hypothermia to "buy time": one in trauma patients suffering cardiac arrest, to enable surgical repair, and the other in patients who unexpectedly die in the ED, to enable organ donation...
May 2017: American Journal of Bioethics: AJOB
https://www.readbyqxmd.com/read/28430013/barriers-to-access-to-sterile-syringes-as-perceived-by-pharmacists-and-injecting-drug-users-implications-for-harm-reduction-in-lebanon
#16
Ali Ghaddar, Karine Nassar, Ghadier Elsoury
BACKGROUND: Access to sterile syringes to injecting drug users (IDU) reduces sharing behavior and prevents the transmission of HIV. OBJECTIVES: To describe the barriers to access to sterile syringes for IDUs in Lebanon from the perspectives of pharmacists and IDUs. METHODS: in this qualitative study conducted in Lebanon, data were collected from 72 syringe purchase tests at pharmacies, 64 interviewees with pharmacists and 2 focus groups with injecting drug users...
April 21, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28429540/silencing-of-astrocyte-elevated-gene-1-inhibits-proliferation-and-migration-and-induces-apoptosis-in-melanoma
#17
Yue Zhang, Ge Peng, Ying Wang, Lixia Cui, Wenqing Wu, Luan Wang, Chengyu Liu, Xiuping Han
Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of ras and c-myc, has been implicated in the development of multiple tumors, yet its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing of AEG-1 inhibited proliferation of melanoma cells and induced cell cycle arrest, accompanied by reduced levels of cyclinA, cyclinB, cyclinD1, cyclinE and cyclin dependent kinase 2...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28428943/pathogenic-variant-in-nlrp7-19q13-42-associated-with-recurrent-gestational-trophoblastic-disease-data-from-early-embryo-development-observed-during-in-vitro-fertilization
#18
E Scott Sills, Alexandra J Obregon-Tito, Harry Gao, Thomas K McWilliams, Anthony T Gordon, Catharine A Adams, Rima Slim
OBJECTIVE: To describe in vitro development of human embryos derived from an individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect. METHODS: A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, in vitro fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening...
March 2017: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28428939/effects-of-sperm-insemination-on-the-final-meiotic-maturation-of-mouse-oocytes-arrested-at-metaphase-i-after-in-vitro-maturation
#19
Jeong Yoon, Kyoung-Mi Juhn, San-Hyun Yoon, Yong Ko, Jin-Ho Lim
OBJECTIVE: The aims of this study were to investigate whether fertilization could induce the resumption of meiosis in mouse oocytes arrested at metaphase I (MI) after in vitro maturation (IVM), and to investigate the effect of Ca(2)(+) chelator treatment at the time of fertilization on the transition from MI to metaphase II (MII). METHODS: MII-stage and arrested MI-stage mouse oocytes after IVM were fertilized, and then embryonic development was monitored. Blastocysts from each group were transferred into 2...
March 2017: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28427191/down-regulation-of-long-non-coding-rna-rp11-708h21-4-is-associated-with-poor-prognosis-for-colorectal-cancer-and-promotes-tumorigenesis-through-regulating-akt-mtor-pathway
#20
Longci Sun, Chunhui Jiang, Chunjie Xu, Hanbing Xue, Hong Zhou, Lei Gu, Ye Liu, Qing Xu
Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, through next generation RNA sequencing and experimental validations, we determined the expression status of RP11-708H21.4 in colorectal cancer (CRC) and explored its clinical significance and biological functions in CRC. Differentially expressed lncRNAs from CRC samples and corresponding normal mucosa tissues was screened through RNA sequencing, and RP11-708H21.4 was selected for further experimental validation...
March 2, 2017: Oncotarget
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