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https://www.readbyqxmd.com/read/28930776/a-phase1b-dose-escalation-study-of-recombinant-circularly-permuted-trail-in-patients-with-relapsed-or-refractory-multiple-myeloma
#1
Jian Hou, Lugui Qiu, Yaozhong Zhao, Xuejun Zhang, Yan Liu, Zhao Wang, Fang Zhou, Yun Leng, Shifang Yang, Hao Xi, Fuxu Wang, Bing Zhu, Wenming Chen, Peng Wei, Xiangjun Zheng
OBJECTIVES: Circularly permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT), or CPT, is a novel antitumor drug candidate. This phase 1b study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent CPT in patients with relapsed or refractory multiple myeloma (RRMM), and aimed to identify the recommended dose for the phase 2 study. MATERIALS AND METHODS: Patients received single or multiple doses (once daily for 5 consecutive days per 21-d cycle) of CPT intravenous infusion at doses of 5, 6...
September 19, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28930302/-accidental-severe-poisoning-with-methemoglobinogenic-substance-a-case-report
#2
Kinga Rośniak-Bąk, Marek Bąk, Renata Winnicka, Anna Krakowiak
A 45-year-old male patient was admitted to the Regional Poison Center because of poisoning with dimethyloaniline contained in a toxic resin-curing dimethyl aniline-based formulation ingested inadvertently. Intoxication happened at workplace. The patient was then transferred to the Toxicology Clinic, where he stayed for 3 weeks. During the hospitalization, the primary method of treatment involved administration of methylene blue, which is the antidote of choice in such cases. During the intensive care and treatment of the patient massive intravascular hemolysis was seen...
September 20, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28928660/-1-h-nmr-based-metabolomics-study-of-the-toxicological-effects-in-rats-induced-by-renqing-mangjue-pill-a-traditional-tibetan-medicine
#3
Can Xu, Caidan Rezeng, Jian Li, Lan Zhang, Yujing Yan, Jian Gao, Yingfeng Wang, Zhongfeng Li, Jianxin Chen
"RenqingMangjue" pill (RMP), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with different dosages of RMP once a day for 15 consecutive days, then half of the rats were euthanized on the 15th day and the remaining were euthanized on the 30th day...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928090/investigation-of-antidiabetic-potential-of-phyllanthus-niruri-l-using-assays-for-%C3%AE-glucosidase-muscle-glucose-transport-liver-glucose-production-and-adipogenesis
#4
Maliheh Najari Beidokhti, Mia Vesterholm Andersen, Hoda M Eid, Mayra Luz Sanchez Villavicencio, Dan Staerk, Pierre S Haddad, Anna K Jäger
Phyllanthus niruri is used in herbal medicine for treatment of diabetes. The objective of this study was to investigate the antidiabetic potential of P. niruri, using assays for α-glucosidase, muscle glucose transport, liver glucose production and adipogenesis. α-Glucosidase inhibitory activity was performed on aqueous and ethanolic extract of aerial parts of P. niruri. The aqueous and ethanolic extract of P. niruri showed α-glucosidase inhibitory activity with IC50 values of 3.7 ± 1.1 and 6.3 ± 4...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28928020/selenium-induces-the-demethylation-of-mercury-in-marine-fish
#5
Xun Wang, Wen-Xiong Wang
The antagonistic effect of selenium (Se) on mercury (Hg) toxicity has been known for decades. Earlier studies mainly focused on Hg-Se interaction based on biokinetics and bioaccumulation, but the influences of Se on in vivo biotransformation of methylmercury (MeHg) have not been well understood. We conducted a 42-day exposure study to investigate the dynamic changes of MeHg and its primary degradation product - inorganic mercury (IHg) - in different organs of black seabream (Acanthopagrus schlegeli) exposed to different dietary Se levels...
September 16, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28927525/alpha-1-antitrypsin-deficiency-genetic-variations-clinical-manifestations-and-therapeutic-interventions
#6
REVIEW
Younis Mohammad Hazari, Arif Bashir, Mudasir Habib, Samirul Bashir, Huma Habib, M Abul Qasim, Naveed Nazir Shah, Ehtishamul Haq, Jeffrey Teckman, Khalid Majid Fazili
Alpha-1-antitrypsin (AAT) is an acute phase secretory glycoprotein that inhibits neutrophil proteases like elastase and is considered as the archetype of a family of structurally related serine-protease inhibitors termed serpins. Serum AAT predominantly originates from liver and increases three to five fold during host response to tissue injury and inflammation. The AAT deficiency is unique among the protein-misfolding diseases in that it causes target organ injury by both loss-of-function and gain-of-toxic function mechanisms...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28926834/heme-oxygenase-activity-and-heme-binding-in-a-neonatal-mouse-model
#7
Stephanie Kourula, Joyce Ang, Hui Zhao, Flora Kalish, Peter Vandenabeele, Karl G Sylvester, Ronald J Wong, David K Stevenson
BACKGROUND: Severe hemolytic disease of the newborn leads to the release of pro-oxidative free heme (FH). Heme oxygenase (HO) is primarily responsible for detoxifying FH. OBJECTIVE: To investigate the protective effects of HO in a model of heme overload. METHODS: For in vitro studies, NIH3T3 HO-1-luc cells were incubated with 10, 30, or 60 µM FH or methemalbumin (MHA). HO-1 promoter activity was assessed 3, 6, and 24 h after treatment. Cell survival was indexed by viability assays...
September 20, 2017: Neonatology
https://www.readbyqxmd.com/read/28925992/efficacy-of-combining-ing4-and-trail-genes-in-cancer-targeting-gene-virotherapy-strategy-first-evidence-in-preclinical-hepatocellular-carcinoma
#8
A G El-Shemi, A M Ashshi, E Oh, B-K Jung, M Basalamah, A Alsaegh, C-O Yun
Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4); as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); as potent-apoptosis inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono-and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC...
September 19, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28925715/novel-carbon-dots-derived-from-schizonepetae-herba-carbonisata-and-investigation-of-their-haemostatic-efficacy
#9
Meiling Zhang, Yan Zhao, Jinjun Cheng, Xiaoman Liu, Yongzhi Wang, Xin Yan, Yue Zhang, Fang Lu, Qingguo Wang, Huihua Qu
Schizonepetae Herba Carbonisata (SHC) has been used in traditional Chinese medicine (TCM) to treat haemorrhagic diseases for more than 1000 years. However, little information is available on its haemostatic components and mechanism. In this study, we developed novel water-soluble carbon dots (CDs) in aqueous extracts of SHC for the first time and a modified pyrolysis method was used to prepare the SHC using Schizonepetae Herba (SH) as the sole precursor. The SHC-CDs were characterized using transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transform infrared (FT-IR), ultraviolet-visible (UV-Vis) and fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and high-performance liquid chromatography (HPLC)...
September 19, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28925102/continued-alcohol-misuse-in-human-cirrhosis-is-associated-with-an-impaired-gut-liver-axis
#10
Jasmohan S Bajaj, Genta Kakiyama, Derrick Zhao, Hajime Takei, Andrew Fagan, Phillip Hylemon, Huiping Zhou, William M Pandak, Hiroshi Nittono, Oliver Fiehn, Nita Salzman, Mary Holtz, Pippa Simpson, Edith A Gavis, Douglas M Heuman, Runping Liu, Dae Joong Kang, Masoumeh Sikaroodi, Patrick M Gillevet
BACKGROUND: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear. AIM: Determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients. METHODS: Age and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection...
September 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28924552/schisandra-sphenanthera-extract-wuzhi-tablet-protects-against-chronic-binge-and-acute-alcohol-induced-liver-injury-by-regulating-the-nrf2-are-pathway-in-mice
#11
Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#12
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923870/associations-between-voriconazole-therapeutic-drug-monitoring-toxicity-and-outcome-in-liver-transplant-patients-an-observational-study
#13
Zahra Hashemizadeh, Parisa Badiee, Seyed Ali Malekhoseini, Hadi Raeisi Shahraki, Bita Geramizadeh, Hashem Montaseri
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923573/neoadjuvant-buparlisib-plus-trastuzumab-and-paclitaxel-for-women-with-her2-primary-breast-cancer-a-randomised-double-blind-placebo-controlled-phase-ii-trial-neophoebe
#14
Sibylle Loibl, Lorena de la Pena, Valentina Nekljudova, Dimitrios Zardavas, Stefan Michiels, Carsten Denkert, Mahdi Rezai, Begoña Bermejo, Michael Untch, Soo Chin Lee, Sabine Turri, Patrick Urban, Sherko Kümmel, Guenther Steger, Andrea Gombos, Michael Lux, Martine J Piccart, Gunter Von Minckwitz, José Baselga, Sherene Loi
AIM: The Neoadjuvant PI3K inhibition in HER2 OverExpressing Breast cancEr (NeoPHOEBE) trial evaluated the efficacy and safety of buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, plus trastuzumab and paclitaxel as neoadjuvant treatment for human epidermal growth factor receptor-2 positive (HER2+) breast cancer. METHODS: NeoPHOEBE was a neoadjuvant, phase II, randomised, double-blind study. Women with HER2+ breast cancer were randomised within two independent cohorts by PIK3CA mutation status and, in each cohort stratified by oestrogen receptor (ER) status to receive buparlisib or placebo plus trastuzumab (first 6 weeks) followed by buparlisib or placebo with trastuzumab and paclitaxel...
September 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28923436/changes-in-hepatic-gene-expression-and-serum-metabolites-after-oral-administration-of-overdosed-vitamin-e-loaded-nanoemulsion-in-rats
#15
Chae Young Park, Chul Ho Jang, Do Yup Lee, Hyung Taek Cho, Young Jun Kim, Yoo Heon Park, Jee-Young Imm
Vitamin-E-loaded nanoemulsion (Vit E-NE) was produced, and the effects of repeated oral administration of Vit E-NE (2 g/kg/day) for five days on hepatic gene expression and serum metabolites were investigated in rats. The mean particle diameter and zeta potential of Vit E-NE was 112 nm and 56 mV, respectively. Vit E-NE administered rats showed significantly higher triglyceride content than of standard diet (control) or Vit E control emulsion (Vit E-CE) group but no toxicity symptoms were found in blood biochemical analysis...
September 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28922724/oyster-ostrea-plicatula-gmelin-polysaccharides-intervention-ameliorates-cyclophosphamide-induced-genotoxicity-and-hepatotoxicity-in-mice-via-the-nrf2-are-pathway
#16
Shuting Lin, Gengxin Hao, Min Long, Fei Lai, Qingqin Li, Yongmei Xiong, Yan Tian, Dong Lai
In this study, we explored the protective effects of oyster (Ostrea plicatula Gmelin) polysaccharides (OPS) against genotoxicity and liver injury induced by cyclophosphamide (CP) in BALB/c mice. OPS was administered to mice at doses of 100 and 200mg/kg for 7 consecutive days, then 50mg/kg CP was injected via abdomen. Then mice were sacrificed and samples were collected. Bone marrow micronuclei (MN) and polychromatic erythrocytes (PCE): normochromatic erythrocytes (NCE) ratio were calculated to evaluate CP induced genetic toxicity...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28921839/hepatoblastoma-in-children-aged-less-than-six-months-at-diagnosis-a-report-from-the-siopel-group
#17
Patrizia Dall'Igna, Laurence Brugieres, Anne Sanlaville Christin, Rudolf Maibach, Michela Casanova, Rita Alaggio, Jean de Ville de Goyet, Jozsef Zsiros, Bruce Morland, Piotr Czauderna, Margaret Childs, Daniel C Aronson, Sophie Branchereau, Penelope Brock, Giorgio Perilongo
BACKGROUND: The purpose of this study was to evaluate clinical characteristics, treatment, and survival of children, who were diagnosed with hepatoblastoma (HB) in their first 6 months of age, enrolled in the SIOPEL 2 and 3 protocols. METHODS: Seventy-nine patients, treated between 1994 and 2006, were analyzed after stratification into three age groups: <1 month, between 1 and 3 months, and between 3 and 6 months. All received preoperative chemotherapy. RESULTS: Clinical characteristics were similar in both trials: 4 patients had pulmonary metastases at diagnosis, 4 had α-fetoprotein <100 ng/ml, 68 were operated by partial hepatectomy, and 7 received liver transplant...
September 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28920500/acute-toxicity-of-the-bowel-after-stereotactic-robotic-radiotherapy-for-abdominopelvic-oligometastases
#18
Michael Frelinghuysen, Wilco Schillemans, Lieke Hol, Cornelis Verhoef, Mischa Hoogeman, Joost Jan Nuyttens
AIM: To correlate dose-volume histogram (DVH) parameters with appearance of grade ≥2 acute and late gastrointestinal toxicity of stereotactic body radiotherapy (SBRT) in patients with abdominopelvic solitary or oligometastatic disease outside the liver. MATERIAL AND METHODS: Acute and late bowel toxicity of 84 abdominopelvic oligometastatic patients was registered. A logistic regression was performed between different DVH parameters and presence of grade ≥2 acute and late toxicity...
September 18, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28920396/-inhibition-of-chitin-oligosaccharide-on-dyslipidemia-and-the-potential-molecular-mechanism-exploration
#19
Fanqi Yi, Junping Zheng, Qiongyu Li, Siming Jiao, Yuguang Du, Yun Ye, Hongtao Liu
The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks...
April 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28919858/safety-evaluation-of-sclerotium-from-a-medicinal-mushroom-lignosus-cameronensis-cultivar-preclinical-toxicology-studies
#20
Sook-Shien Lee, Nget-Hong Tan, Jayalakshmi Pailoor, Shin-Yee Fung
Twenty-eight days subacute toxicity studies performed in rats using sclerotial powder of Lignosus cameronensis cultivar was conducted to assess its safety for consumption prior to other scientific investigations on its medicinal benefits, nutraceutical or pharmaceutical application of the mushroom. The study was conducted at 250, 500, and 1000 mg/kg sclerotial powder of L. cameronensis cultivar (n = 5 for each respective dose, on both male and female groups) while control groups received only distilled water...
2017: Frontiers in Pharmacology
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