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https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#1
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29332196/bioelectronic-modulation-of-carotid-sinus-nerve-activity-in-the-rat-a-potential-therapeutic-approach-for-type-2-diabetes
#2
Joana F Sacramento, Daniel J Chew, Bernardete F Melo, Matteo Donegá, Wesley Dopson, Maria P Guarino, Alison Robinson, Jesus Prieto-Lloret, Sonal Patel, Bradley J Holinski, Nishan Ramnarain, Victor Pikov, Kristoffer Famm, Silvia V Conde
AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29330240/structured-management-of-chronic-nonmalignant-pain-with-opioids-in-a-rural-primary-care-office
#3
Kevin S McCann, Shawndra Barker, Raymond Cousins, Adam Franks, Clinton McDaniel, Stephen Petrany, Eric Riley
INTRODUCTION: The use of opioid medication for nonmalignant chronic pain (NMCP) increased dramatically during the last 20 years. There have been regulatory changes implemented to reduce the risk of harm to both patients and society. Much of the burden of monitoring these patients is falling on primary care physicians (PCPs), who do not have the time or resources to handle what is entailed in a best-practice approach to NMCP. METHODS: A retrospective study was conducted with all patients on opioid medication for NMCP who were enrolled onto an individual PCP's practice...
January 2018: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/29329593/targeting-ectodysplasin-promotor-by-crispr-dcas9-effector-effectively-induces-the-reprogramming-of-human-bone-marrow-derived-mesenchymal-stem-cells-into-sweat-gland-like-cells
#4
Sujing Sun, Jun Xiao, Jiahui Huo, Zhijun Geng, Kui Ma, Xiaoyan Sun, Xiaobing Fu
BACKGROUND: Patients with a deep burn injury are characterized by losing the function of perspiration and being unable to regenerate the sweat glands. Because of their easy accession, multipotency, and lower immunogenicity, bone marrow-derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source for cell therapy. The aim of this study was to identify whether targeting the promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce the BM-MSCs to differentiate into sweat gland-like cells (SGCs)...
January 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29328482/cytisine-induces-endoplasmic-reticulum-stress-caused-by-calcium-overload-in-hepg2-cells
#5
Lei Yu, Bo Jiang, Zhifeng Chen, Xin Wang, Dongxue Shang, Xiaopo Zhang, Yongxue Sun, Jinghui Yang, Yubin Ji
Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway...
January 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328465/effects-of-diphyllin-as-a-novel-v-atpase-inhibitor-on-te-1-and-eca-109-cells
#6
Haijiao Chen, Pengfei Liu, Ting Zhang, Yi Gao, Yingdi Zhang, Xiuyun Shen, Xiao Li, Weidong Shen
Diphyllin is a natural component of traditional Chinese medicine, which effectively inhibits V-ATPase activity and affects the progression of cancer. However, few studies have been conducted on esophageal cancer, and the mechanisms remain to be elucidated. The present study revealedthat diphyllin inhibited proliferation and induced S arrest in esophageal cancer cell lines TE-1 and ECA-109. Further experiments revealed that diphyllin inhibited V-ATPase activity and decreased the mRNA expression of mammalian target of rapamycin complex 1 (mTORC1), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF)...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328001/gamma-knife-radiosurgery-of-saccular-aneurysms-in-a-rabbit-model
#7
Mark D Meadowcroft, Timothy K Cooper, Sebastian Rupprecht, Thaddeus C Wright, Elizabeth E Neely, Michele Ferenci, Weimin Kang, Qing X Yang, Robert E Harbaugh, James R Connor, James McInerney
OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with neurological morbidity and mortality due to risk of rupture. In addition, many aneurysm treatments have associated risk profiles that can preclude the prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS) is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous malformations. Aneurysms associated with arteriovenous malformations have been noted to resolve after treatment of the malformation...
January 12, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29327570/the-detour-procedure-no-more-need-for-conventional-bypass-surgery
#8
Dainis Krievins, Janis Savlovskis, Natalija Ezite, Andrew Hill, Kaspars Kisis, Marcis Gedins, Edgars Zellans, Andrew Holden
BACKGROUND: Long segment occlusive disease in the superficial femoral artery remains a treatment challenge despite advances in open surgical and endovascular approaches. We report initial clinical results of an entirely new procedure to perform femoropopliteal bypass using the DETOUR System to create a stentgraft bypass which originates in the SFA, travels through the femoral vein, and ends in the popliteal artery, bypassing the diseased segment. METHODS: Review the initial results of the first five patients at a single site enrolled in IRB-approved, prospective clinical study using the DETOUR System...
January 9, 2018: Journal of Cardiovascular Surgery
https://www.readbyqxmd.com/read/29327174/localized-targeted-antiangiogenic-drug-delivery-for-glioblastoma
#9
REVIEW
Gregory D Arnone, Abhiraj D Bhimani, Tania Aguilar, Ankit I Mehta
Systemic delivery of antiangiogenic agents has been ineffective in improving the overall survival of patients with both primary and recurrent glioblastoma, in part due to dose-limiting toxicities. With the development of new and efficient localized delivery methods and vehicles, an otherwise lethal dose of antiangiogenic chemotherapy can be used to treat tumors while minimizing systemic side effects. Current in-vitro and in-vivo animal studies have shown promising results that encourage the pursuit towards human clinical trials for localized antiangiogenic treatment in the near future...
January 11, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29325469/current-update-of-a-thermosensitive-liposomes-composed-of-dppc-and-brij78
#10
Laurence Ho, Mehrdad Bokharaei, Shyh-Dar Li
Thermosensitive liposomes (TSLs) have been a prominent area of study in the discipline of tumor-targeted chemotherapeutics. The representative product of TSLs is ThermoDox® (DPPC/lyso-PC/PEG-lipid), which has advanced to Phase III clinical trials. Various groups have sought to develop a new TSL to improve upon the LTSL (lyso-lipid temperature sensitive liposomes) formulation that is used to prepare ThermoDOX®. This review focuses on the development and recent update of an innovative TSL formulation, HaT-liposomes composed of DPPC and Brij78...
January 11, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29325284/-risk-factors-and-therapeutic-strategies-for-primary-biliary-cholangitis-patients-with-poor-prognosis
#11
Y W Shi, H Ma
With the progress in detection methods and the update of diagnostic and therapeutic concepts, more and more patients with primary biliary cholangitis (PBC) have been diagnosed and treated. A high proportion of PBC patients, however, progress to liver decompensation, with an increased risk of liver transplantation and death and a significant reduction in long-term survival. These patients need early diagnosis and urgent treatment. This article discusses how to identify the PBC patients with poor prognosis early from the aspects of biochemical response, disease features, and biomarkers, and reviews the progress in related complementary therapies and new drugs including Ocaliva, Fibrates, UDCA-derived drugs, and molecular targeted drugs...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29324571/physical-activity-patterns-and-sedentary-behavior-in-older-women-with-urinary-incontinence-an-accelerometer-based-study
#12
Christine M Chu, Kavita D Khanijow, Kathryn H Schmitz, Diane K Newman, Lily A Arya, Heidi S Harvie
PURPOSE: Objective physical activity data for women with urinary incontinence are lacking. We investigated the relationship between physical activity, sedentary behavior, and the severity of urinary symptoms in older community-dwelling women with urinary incontinence using accelerometers. MATERIALS AND METHODS: This is a secondary analysis of a study that measured physical activity (step count, moderate-to-vigorous physical activity time) and sedentary behavior (percentage of sedentary time, number of sedentary bouts per day) using a triaxial accelerometer in older community-dwelling adult women not actively seeking treatment of their urinary symptoms...
January 10, 2018: Female Pelvic Medicine & Reconstructive Surgery
https://www.readbyqxmd.com/read/29324517/long-term-care-of-transplant-recipients-de-novo-neoplasms-after-liver-transplantation
#13
Patrizia Burra, Sarah Shalaby, Alberto Zanetto
PURPOSE OF REVIEW: Since the first liver transplantation in the early 1960s, there have been significant improvements in the recipients' long-term outcome. Patients who have undergone transplantation are exposed to a high risk of developing neoplastic disease, not only because of their chronic immunosuppression, but also related to physiological aging, lifestyle, chronic viral infections, liver disease cause, and carcinogenic immunosuppressants. The present review covers the latest and most relevant data on de novo neoplasms after liver transplantation, and discusses their implications for clinical practice...
January 9, 2018: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29323739/fasudil-alleviates-pressure-overload-induced-heart-failure-by-activating-nrf2-mediated-antioxidant-responses
#14
Peng Guan, Yingran Liang, Na Wang
The RhoA/Rho-kinase cascade plays an important role in many aspects of cardiovascular function. This study aims to investigate the protective effects of fasudil, a Rho-kinase inhibitor, on pressure overload induced heart failure in rats. Pressure overload induced heart failure was induced in SD rats by banding the abdominal aorta for 8 weeks. The rats were divided into four groups: Sham, TAC, TAC plus low dose of fasudil and TAC plus high dose of fasudil group. Low dose and high dose fasudil were 5 mg/kg/day and 10 mg/kg/day respectively...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29323613/idrugs-and-idevices-discovery-research-preclinical-assays-techniques-and-animal-model-studies-for-ocular-hypotensives-and-neuroprotectants
#15
Najam A Sharif
Discovery ophthalmic research is centered around delineating the molecular and cellular basis of ocular diseases and finding and exploiting molecular and genetic pathways associated with them. From such studies it is possible to determine suitable intervention points to address the disease process and hopefully to discover therapeutics to treat them. An investigational new drug (IND) filing for a new small-molecule drug, peptide, antibody, genetic treatment, or a device with global health authorities requires a number of preclinical studies to provide necessary safety and efficacy data...
January 11, 2018: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29323337/regulatory-t-cells-as-a-new-therapeutic-target-for-atherosclerosis
#16
REVIEW
Han-Xiao Ou, Bing-Bing Guo, Qi Liu, Yu-Kun Li, Zhen Yang, Wen-Jie Feng, Zhong-Cheng Mo
Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. These responses further aggravate vascular inflammation and promote progression of atherosclerosis and vulnerability to plaques via releasing pro-inflammatory cytokines. Regulatory T cells (Tregs) as the major immunoregulatory cells, in particular, induce and maintain immune homeostasis and tolerance by suppressing the immune responses of various cells such as T and B cells, natural killer (NK) cells, monocytes, and dendritic cells (DCs), as well as by secreting inhibitory cytokines interleukin (IL)-10, IL-35 and transcription growth factor β (TGF-β) in both physiological and pathological states...
January 11, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29322610/safety-and-efficacy-of-once-weekly-semaglutide-versus-additional-oral-antidiabetic-drugs-in-japanese-subjects-with-inadequately-controlled-t2d-a-randomised-trial
#17
Kohei Kaku, Yuichiro Yamada, Hirotaka Watada, Atsuko Abiko, Tomoyuki Nishida, Jeppe Zacho, Arihiro Kiyosue
AIMS: Semaglutide is a glucagon-like peptide 1 analogue in development for type 2 diabetes (T2D). Safety and efficacy of once-weekly subcutaneous semaglutide as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional OAD was evaluated in Japanese subjects with T2D inadequately controlled on diet/exercise or OAD monotherapy. METHODS: In this phase 3, open-label trial, adults with T2D were randomised 2:2:1 to semaglutide 0.5 mg or 1.0 mg, or one additional OAD (dipeptidyl peptidase-4 inhibitor, biguanide, sulphonylurea, glinide, α-glucosidase inhibitor or thiazolidinedione) with different modes of action...
January 11, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29321171/sgk1-foxo3-signaling-in-hypothalamic-pomc-neurons-mediates-glucocorticoid-increased-adiposity
#18
Yalan Deng, Yuzhong Xiao, Feixiang Yuan, Yaping Liu, Xiaoxue Jiang, Jiali Deng, Geza Fejes-Toth, Aniko Naray-Fejes-Toth, Shanghai Chen, Yan Chen, Hao Ying, Qiwei Zhai, Yousheng Shu, Feifan Guo
Although central nervous system has been implicated in glucocorticoid-induced fat mass gain, the underlying mechanisms are poorly understood. The aim of our current study was to investigate the possible involvement of hypothalamic serum- and glucocorticoid-regulated kinase 1 (SGK1) in glucocorticoid-increased adiposity. It is well-known that SGK1 expression is induced by acute glucocorticoid treatment, interestingly, we found its expression was decreased in the arcuate nucleus of the hypothalamus, including POMC neurons, following chronic dexamethasone (Dex) treatment...
January 10, 2018: Diabetes
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#19
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29320894/biomarkers-of-tumor-redox-status-in-response-to-modulations-of-glutathione-and-thioredoxin-antioxidant-pathways
#20
Julie Kengen, Jean-Philippe Deglasse, Marie-Aline Neveu, Lionel Mignion, Céline Desmet, Florian Gourgue, Jean-Christophe Jonas, Bernard Gallez, Bénédicte F Jordan
The ability of certain cancer cells to maintain a highly reduced intracellular environment is correlated with aggressiveness and drug resistance. Since the gluthathione (GSH) and thioredoxin (TRX) systems cooperate to a tight regulation of ROS in cell physiology, and to a stimulation of tumor initiation and progression, modulation of the GSH and TRX pathways are emerging as new potential targets in cancer. In vivo methods to assess changes in tumor redox status are critically needed to assess the relevance of redox-targeted agents...
January 10, 2018: Free Radical Research
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