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Drug induced diseases

Zhenhua Miao, Linda S Ertl, Dale Newland, Bin Zhao, Yu Wang, Xiaoping Zang, James J Campbell, Xiaoli Liu, Ton Dang, Shichang Miao, Antoni Krasinski, Sreenivas Punna, Yibin Zeng, Jeffrey McMahon, Penglie Zhang, Israel F Charo, Thomas J Schall, Rajinder Singh
Focal segmental glomerulosclerosis (FSGS) comprises a group of uncommon disorders that present with marked proteinuria, nephrotic syndrome, progressive renal failure and characteristic glomerular lesions on histopathology. The current standard of care for patients with FSGS include immunosuppressive drugs such as glucocorticoids followed by calcineurin inhibitors, if needed for intolerance or inadequate response to glucocorticoids. Renin-angiotensin-aldosterone (RAAS) blockers are also used to control proteinuria, an important signature of FSGS...
2018: PloS One
Beatrice Xuan Ho, Nicole Min Qian Pek, Boon-Seng Soh
The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo...
March 21, 2018: International Journal of Molecular Sciences
Liang Ouyang, Lan Zhang, Shouyue Zhang, Dahong Yao, Yuqian Zhao, Guan Wang, Leilei Fu, Peng Lei, Bo Liu
UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86 and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SY5Y cells...
March 21, 2018: Journal of Medicinal Chemistry
Jorge A Avila, Roseanna M Zanca, Denis Shor, Nicholas Paleologos, Amber A Alliger, Maria E Figueiredo-Pereira, Peter A Serrano
Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA...
February 2018: Heliyon
Hao Chan, Hsuan-Shun Huang, Der-Shan Sun, Chung-Jen Lee, Te-Sheng Lien, Hsin-Hou Chang
Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin-angiotensin-aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP)...
February 27, 2018: Oncotarget
Sylvain Chateau, Umberto D'Ortona, Sébastien Poncet, Julien Favier
The fluid transport and mixing induced by beating cilia, present in the bronchial airways, are studied using a coupled lattice Boltzmann-Immersed Boundary solver. This solver allows the simulation of both single and multi-component fluid flows around moving solid boundaries. The cilia are modeled by a set of Lagrangian points, and Immersed Boundary forces are computed onto these points in order to ensure the no-slip velocity conditions between the cilia and the fluids. The cilia are immersed in a two-layer environment: the periciliary layer (PCL) and the mucus above it...
2018: Frontiers in Physiology
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
Yue Zhang, Liying Zhang, Qi Zhang, Xitong Zhang, Tong Zhang, Bing Wang
Background: Brucea javanica oil (BJO), a traditional Chinese herbal medicine, has a variety of pharmacological activities and several BJO-related patent drugs have been widely used in China. Purpose: The objective of this study was to evaluate the gastric therapeutic effects of self-made BJO and its pharmaceutical potential to formulate novel BJO gastroretentive floating bead by comparing with commercial products. Methods: BJO was extracted from the seeds of B...
2018: Drug Design, Development and Therapy
Tanusree Sen, Pampa Saha, Nilkantha Sen
Acetylation of the microtubule-associated protein tau promotes its polymerization into neurofibrillary tangles that are implicated in the pathology of Alzheimer's disease (AD). The gaseous neurotransmitter nitric oxide (NO) regulates cell signaling through the nitrosylation of proteins. We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42 ), a peptide that is also implicated in AD...
March 20, 2018: Science Signaling
Pennapa Chonpathompikunlert, Phetcharat Boonruamkaew, Wanida Sukketsiri, Pilaiwanwadee Hutamekalin, Morakot Sroyraya
BACKGROUND: Apium graveolens L. is a traditional Chinese medicine prescribed as a treatment for hypertension, gout, and diabetes. This study aimed to determine the neuroprotective effects of A. graveolens extract against a Parkinson's disease (PD) model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6 mice. METHODS: Male C57BL/6 mice treated with MPTP were orally dosed with A. graveolens extract daily for 21 days. Behavioral tests, including a rotarod apparatus, a narrow beam test, a drag test, a grid walk test, a swimming test, and a resting tremor evaluation, were performed...
March 20, 2018: BMC Complementary and Alternative Medicine
Yoon-Young Sung, Dong-Seon Kim, Seung-Hyung Kim, Ho Kyoung Kim
BACKGROUND: Allium fistulosum (Welsh onion) is a traditional medicinal plant used for the treatment of colds, influenza, abdominal pain, headache, and heart disease. This study evaluated the effects of A. fistulosum ethanolic extract (AFE) and aqueous extract (AFW) on body weight and other obesity-related parameters. METHODS: Male 8-week-old C57BL/6 J mice were fed either a standard chow diet (normal control) or a high-fat diet (HFD) either alone (HFD-control) or in combination with G...
March 20, 2018: BMC Complementary and Alternative Medicine
Modi Wang, Moloud A Sooreshjani, Clinton Mikek, Clement Opoku-Temeng, Herman O Sintim
AIM: Persistent activation of STING pathway is the basis for several autoimmune diseases. STING is activated by cGAMP, which is produced by cGAS in the presence of DNA. Results/methodology: HPLC-based medium throughput screening for inhibitors of cGAS identified suramin as a potent inhibitor. Unlike other reported cGAS inhibitors, which bind to the ATP/GTP binding site, suramin displaced the bound DNA from cGAS. Addition of suramin to THP1 cells reduced the levels of IFN-β mRNA and protein...
March 21, 2018: Future Medicinal Chemistry
Alireza Vakilian, Seyed Moein Razavi-Nasab, Ali Ravari, Tayebeh Mirzaei, Amir Moghadam-Ahmadi, Nazanin Jalali, Reza Bahramabadi, Mohammadtaghi Rezayati, Amin Yazdanpanah-Ravari, Farhad Bahmaniar, Mohammad Reza Bagheri, Mahmood Sheikh Fathollahi, Gholamreza Asadikaram, Mohammad Kazemi Arababadi
INTRODUCTION: Patients with Alzheimer disease (AD) suffer from psychotic symptoms including pain. The current antipsychotic drugs confer limited effectiveness, and hence new strategies are being designed to decrease pain in order to increase antipsychological effectiveness. Vitamin B12 is a safe supplementary drug to decrease pain. Additionally, cytokines participate in the pathogenesis of immune-related diseases such as AD. Thus, the main aim of this clinical trial study was to determine the effects of treatment with risperidone and quetiapine, as antipsychotic drugs, with and without vitamin B12 on the psychotic symptoms of AD patients and the expression of IL-6, IL-8, tumor growth factor (TGF)-β, tumor necrosis factor (TNF)-α, and endothelin (ET)-1)...
March 20, 2018: Neuroimmunomodulation
Yoon Hee Park, Soyeon Cho, Jeong Yee, Jae Youn Kim, Sandy Jeong Rhie, Hye Sun Gwak
Gefitinib is an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for non-small-cell lung cancer with EGFR mutations. Although a few studies have analyzed the causes of gefitinib-induced hepatotoxicity, research focusing on the time intervals before and after hepatotoxicity has yet to be reported. Therefore, this study investigated two types of factors: the time to reach gefitinib-induced hepatotoxicity and the time for recovery. From January 2013 to December 2014, a retrospective study was carried out on 473 non-small-cell lung cancer patients who were treated with gefitinib...
March 19, 2018: Anti-cancer Drugs
Hsin-Hua Li, Chih-Li Lin, Chien-Ning Huang
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD). In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ) levels by affecting amyloid precursor protein (APP) cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD...
February 2018: Neural Regeneration Research
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
Raffaele Altara, Fouad A Zouein, Rita Dias Brandão, Saeed N Bajestani, Alessandro Cataliotti, George W Booz
Standard therapies for heart failure with preserved ejection fraction (HFpEF) have been unsuccessful, demonstrating that the contribution of the underlying diastolic dysfunction pathophysiology differs from that of systolic dysfunction in heart failure and currently is far from being understood. Complicating the investigation of HFpEF is the contribution of several comorbidities. Here, we selected three established rat models of diastolic dysfunction defined by three major risk factors associated with HFpEF and researched their commonalities and differences...
2018: Frontiers in Cardiovascular Medicine
Monia Cito, Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure...
March 2018: Endocrine Connections
Lívia de Figueiredo Diniz, Ana Lia Mazzeti, Ivo Santana Caldas, Isabela Ribeiro, Maria Terezinha Bahia
Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. A first set of experiments assessed the range of E1224 doses required to induce parasitological cure using T. cruzi strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing the death, however, parasitological cure was observed only in mice infected with Y strain...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Tuan Hiep Tran, Thi Thu Phuong Tran, Hanh Thuy Nguyen, Cao Dai Phung, Jee-Heon Jeong, Martina H Stenzel, Sung Giu Jin, Chul Soon Yong, Duy Hieu Truong, Jong Oh Kim
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade...
March 16, 2018: International Journal of Pharmaceutics
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