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https://read.qxmd.com/read/30888659/health-benefits-of-anti-aging-drugs
#1
Veronika Piskovatska, Olha Strilbytska, Alexander Koliada, Alexander Vaiserman, Oleh Lushchak
Aging, as a physiological process mediated by numerous regulatory pathways and transcription factors, is manifested by continuous progressive functional decline and increasing risk of chronic diseases. There is an increasing interest to identify pharmacological agents for treatment and prevention of age-related disease in humans. Animal models play an important role in identification and testing of anti-aging compounds; this step is crucial before the drug will enter human clinical trial or will be introduced to human medicine...
2019: Sub-cellular Biochemistry
https://read.qxmd.com/read/30888649/pulmonary-diseases-and-ageing
#2
Peter J Barnes
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis are regarded as a diseases of accelerated lung ageing and show all of the hallmarks of ageing, including telomere shortening, cellular senescence, activation of PI3 kinase-mTOR signaling, impaired autophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profiles, immunosenescence and a low grade chronic inflammation due to senescence-associated secretory phenotype (SASP). Many of these ageing mechanisms are driven by exogenous and endogenous oxidative stress...
2019: Sub-cellular Biochemistry
https://read.qxmd.com/read/30888600/outcomes-of-hospital-acquired-acute-kidney-injury-in-elderly-patients-a-single-centre-study
#3
Shivendra Singh, Prem Shankar Patel, Prodip Kumar Doley, Shiv Shankar Sharma, Mohd Iqbal, Anupam Agarwal, Neelam Singh, Alok Kumar
BACKGROUND: HAAKI is a common clinical problem in hospitalized patients. Its incidence is high in older patients and carries worse prognosis. The presence of multiple co-morbidities, aging process, and frequent diagnostic and therapeutic interventions predispose elderly patients to HAAKI. This study aims to evaluate the spectrum, risk factors and determinants of outcome of elderly patients with HAAKI. METHODS: This prospective study was conducted during January 2014 to September 2015 in the Department of nephrology, Institute of Medical Sciences, BHU, Varanasi, UP, India...
March 19, 2019: International Urology and Nephrology
https://read.qxmd.com/read/30888358/microfluidic-device-for-expedited-tumor-growth-towards-drug-evaluation
#4
Christopher George Uhl, Yaling Liu
Patient derived organoids have emerged as robust preclinical models for screening anti-cancer therapeutics. Current 2D culturing methods do not provide physiological responses to therapeutics, therefore 3D models are being developed to better reproduce physiological responses. 3D culturing however often requires large initial cell populations and one week to one month to grow tumors ready for therapeutic testing. As a solution a 3D culturing system has been developed capable of producing physiologically relevant tumors in an expedited fashion while only requiring a small number of initial cancer cells...
March 19, 2019: Lab on a Chip
https://read.qxmd.com/read/30888074/pharmacokinetics-metabolism-and-excretion-of-celecoxib-a-selective-cyclooxygenase-2-inhibitor-in-horses
#5
Michael Benedict Subhahar, Jaipaul Singh, Peter Henry Albert, Ahmed Mahmoud Kadry
Celecoxib, a nonsteroidal anti-inflammatory drug, is frequently used to treat arthritis in humans with minimal gastrointestinal side effect compared to traditional NSAIDs. The primary aim of this study was to determine the pharmacokinetic profile of celecoxib-a selective cyclooxygenase-2 (COX-2) inhibitor in horses. Six horses were administered a single oral dose of celecoxib at 2 mg/kg (body weight). After oral dosing, the drug reached a maximum concentration (mean ± SD) in blood of 1,088 ± 324 ng/ml in 4...
March 19, 2019: Journal of Veterinary Pharmacology and Therapeutics
https://read.qxmd.com/read/30888034/rationale-and-study-design-of-a-randomized-clinical-trial-of-metformin-to-prevent-frailty-in-older-adults-with-pre-diabetes
#6
Sara E Espinoza, Nicolas Musi, Chen-Pin Wang, Joel Michalek, Beverly Orsak, Terry Romo, Becky Powers, Alicia Conde, Melody Moris, Darcy Bair-Kelps, Yan Li, Vinutha Ganapathy, Tyson E Jergensen, Lauri C Kelly, Rozmin Jiwani
BACKGROUND: Frailty is a geriatric syndrome that leads to poor health outcomes with aging. Previous studies have demonstrated that insulin resistance and inflammation predict frailty onset. Metformin is a widely-used, well-tolerated drug that improves insulin sensitivity and displays anti-inflammatory properties. It is also known to prevent diabetes onset in adults with pre-diabetes. We hypothesize that metformin in older adults with pre-diabetes will promote healthy aging and prevent frailty...
March 19, 2019: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://read.qxmd.com/read/30887920/tamarix-articulata-t-articulata-an-important-halophytic-medicinal-plant-with-potential-pharmacological-properties
#7
Abdullah M Alnuqaydan, Bilal Rahb
BACKGROUND: Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since immemorial. METHODS: Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords...
March 18, 2019: Current Pharmaceutical Biotechnology
https://read.qxmd.com/read/30887884/exploration-of-interaction-mechanism-of-tyrosol-as-a-potent-anti-inflammatory-agent
#8
Tara Chand Yadav, Naresh Kumar, Utkarsh Raj, Nidhi Goel, Pritish Kumar Vardawaj, Ramasare Prasad, Vikas Pruthi
Drug discovery for a vigorous and feasible lead candidate is a challenging scientific mission as it requires expertise, experience, and huge investment. Natural products and their derivatives having structural diversity are renowned source of therapeutic agents since many years. Tyrosol (a natural phenylethanoid) has been extracted from olive oil, and its structure was confirmed by elemental analysis, FT-IR, FT-NMR, and single crystal X-ray crystallography. The conformational analysis for tyrosol geometry was performed by Gaussian 09 in terms of density functional theory...
March 19, 2019: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/30887822/bioanalytical-challenges-and-unique-considerations-to-support-pharmacokinetic-characterization-of-bispecific-biotherapeutics
#9
Mark Ma, Kelly Colletti, Tong-Yuan Yang, Sheldon Leung, Susan Pederson, Charles S Hottenstein, Xiaohui Xu, Dominic Warrino, Eric Wakshull
Compared with conventional (monospecific) therapeutics, bispecific protein therapeutics present unique challenges for pharmacokinetic (PK) characterization - namely, the characterization of multiple functional domains as well as the consideration of biotransformation or interference by the formation of antitherapeutic antibodies against each functional domain. PK characterization is essential to the success of the overall drug development plan and for molecules with multiple binding domains; multiple bioanalytical methods may be needed to answer critical questions for each phase of drug development...
March 19, 2019: Bioanalysis
https://read.qxmd.com/read/30887570/a-randomized-controlled-phase-ii-clinical-trial-of-%C3%AE-d-mannuronic-acid-m2000-in-pre-surgical-breast-cancer-patients-at-early-stage-t1-t2
#10
Sarvenaz Kashefi, Ramesh Omranipour, Habibollah Mahmoodzadeh, Hamid Ahmadi, Afsaneh Alikhassi, Mostafa Hosseini, Salvatore Cuzzocrea, Bernd H A Rehm, Hidenori Matsuo, Abbas Mirshafiey
Following the potent efficacy of β-D-Mannuronic acid in breast cancer murine model, we evaluated the efficacy of this novel non-steroidal anti-inflammatory drug in breast cancer patients in this present clinical trial. The Study was an 8 weeks randomized, controlled, phase II clinical trial (IRCT: 2017012213739N7 (in 48 pre-surgical breast cancer patients. Patients who had breast cancer at early stage, with invasive ductal carcinoma, were placed on a waiting-list for surgery and were allocated. β-D-Mannuronic was administrated at a dose of two capsules (1000 mg/day) orally during a period of 8 weeks...
March 18, 2019: Clinical and Experimental Pharmacology & Physiology
https://read.qxmd.com/read/30887278/vascular-arginase-is-a-relevant-target-to-improve-cerebrovascular-endothelial-dysfunction-in-rheumatoid-arthritis-evidence-from-the-model-of-adjuvant-induced-arthritis
#11
Romain Bordy, Aurore Quirié, Christine Marie, Daniel Wendling, Perle Totoson, Céline Demougeot
Emerging data revealed that rheumatoid arthritis (RA) is associated with higher risk of cerebrovascular diseases. Whereas cerebral endothelial dysfunction is acknowledged as a critical aspect of cerebrovascular diseases, its presence in RA and the mechanisms involved are currently unknown. By using the model of rat adjuvant-induced arthritis (AIA), the present study investigated cerebrovascular reactivity in pressurized middle cerebral arteries (MCA) on day 33 post-immunization. The results revealed that arthritis induced a dramatic decrease in the vasodilatory response to acetylcholine (ACh), ADP, and bradykinin (n = 7-9 arteries, p < 0...
March 18, 2019: Translational Stroke Research
https://read.qxmd.com/read/30887242/combined-treatment-with-2-hydroxycinnamaldehyde-and-temozolomide-suppresses-glioblastoma-tumorspheres-by-decreasing-stemness-and-invasiveness
#12
Hyewon Jeong, Junseong Park, Jin-Kyoung Shim, Jae Eun Lee, Nam Hee Kim, Hyun Sil Kim, Jong Hee Chang, Jong In Yook, Seok-Gu Kang
INTRODUCTION: Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2'-hydroxycinnamaldehyde (HCA) and its derivative, 2'-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs)...
March 18, 2019: Journal of Neuro-oncology
https://read.qxmd.com/read/30887161/cardiotoxicity-of-targeted-cancer-drugs-concerns-the-cart-before-the-horse-and-lessons-from-trastuzumab
#13
REVIEW
Pierantonio Menna, Giorgio Minotti, Emanuela Salvatorelli
PURPOSE OF REVIEW: Modern oncology is witnessing a renaissance of its pharmacologic armamentarium. Old generation drugs, such as anthracyclines and other cytotoxic or cytostatic drugs, were plagued with a lack of specificity and with the possible occurrence of untoward effects in the cardiovascular system and other healthy tissues. The old drugs are now combined with, or replaced by, new agents that are more specific in attacking some unique moieties and vital functions of cancer cells, causing less noxious effects in healthy tissues...
March 18, 2019: Current Cardiology Reports
https://read.qxmd.com/read/30887081/-therapy-of-pemphigus
#14
REVIEW
N van Beek, D Zillikens, E Schmidt
BACKGROUND: Pemphigus diseases are a heterogeneous group of potentially life-threatening autoimmune bullous disorders. Therefore, rapidly acting and effective therapeutic approaches are essential. OBJECTIVES: In this review, current therapeutic options in line with available guidelines are presented and new therapeutic approaches are discussed. METHODS: A literature search was performed using PubMed. RESULTS: Treatment of pemphigus is based on systemic glucocorticosteroids, frequently combined with potentially corticosteroid-sparing immunosuppressants such as azathioprine and mycophenolate mofetil/mycophenolic acid...
March 18, 2019: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://read.qxmd.com/read/30886871/immunoglobulin-gamma-like-therapeutic-bispecific-antibody-formats-for-tumor-therapy
#15
REVIEW
Shixue Chen, Lingling Li, Fan Zhang, Yu Wang, Yi Hu, Lei Zhao
Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs...
2019: Journal of Immunology Research
https://read.qxmd.com/read/30886620/therapeutic-inhibition-of-the-complement-system-in-diseases-of-the-central-nervous-system
#16
REVIEW
Sarah M Carpanini, Megan Torvell, Bryan Paul Morgan
The complement system plays critical roles in development, homeostasis, and regeneration in the central nervous system (CNS) throughout life; however, complement dysregulation in the CNS can lead to damage and disease. Complement proteins, regulators, and receptors are widely expressed throughout the CNS and, in many cases, are upregulated in disease. Genetic and epidemiological studies, cerebrospinal fluid (CSF) and plasma biomarker measurements and pathological analysis of post-mortem tissues have all implicated complement in multiple CNS diseases including multiple sclerosis (MS), neuromyelitis optica (NMO), neurotrauma, stroke, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD)...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30886609/non-muscle-myosin-ii-role-in-microbial-infection-and-its-potential-as-a-therapeutic-target
#17
REVIEW
Lei Tan, Xiaomin Yuan, Yisong Liu, Xiong Cai, Shiyin Guo, Aibing Wang
Currently, the major measures of preventing and controlling microbial infection are vaccinations and drugs. However, the appearance of drug resistance microbial mounts is main obstacle in current anti-microbial therapy. One of the most ubiquitous actin-binding proteins, non-muscle myosin II (NM II) plays a crucial role in a wide range of cellular physiological activities in mammals, including cell adhesion, migration, and division. Nowadays, growing evidence indicates that aberrant expression or activity of NM II can be detected in many diseases caused by microbes, including viruses and bacteria...
2019: Frontiers in Microbiology
https://read.qxmd.com/read/30886583/experimental-pharmacology-in-transgenic-rodent-models-of-alzheimer-s-disease
#18
A Claudio Cuello, Hélène Hall, Sonia Do Carmo
This Mini Review discusses the merits and shortfalls of transgenic (tg) rodents modeling aspects of the human Alzheimer's disease (AD) pathology and their application to evaluate experimental therapeutics. It addresses some of the differences between mouse and rat tg models for these investigations. It relates, in a condensed fashion, the experience of our research laboratory with the application of anti-inflammatory compounds and S-adenosylmethionine (SAM) at the earliest stages of AD-like amyloid pathology in tg mice...
2019: Frontiers in Pharmacology
https://read.qxmd.com/read/30886324/new-therapeutic-approach-for-targeting-hippo-signalling-pathway
#19
Leticia Dominguez-Berrocal, Erica Cirri, Xiguang Zhang, Laura Andrini, Gustavo H Marin, Sophie Lebel-Binay, Angelita Rebollo
Nuclear localization signals are short amino acid sequences that target proteins for nuclear import. In this manuscript, we have generated a chimeric tri-functional peptide composed of a cell penetrating peptide (CPP), a nuclear localization sequence and an interfering peptide blocking the interaction between TEAD and YAP, two transcription factors involved in the Hippo signalling pathway, whose deregulation is related to several types of cancer. We have validated the cell penetration and nuclear localization by flow cytometry and fluorescence microscopy and shown that the new generated peptide displays an apoptotic effect in tumor cell lines thanks to the specific nuclear delivery of the cargo, which targets a protein/protein interaction in the nucleus...
March 18, 2019: Scientific Reports
https://read.qxmd.com/read/30886307/drug-loaded-hyaluronic-acid-hydrogel-as-a-sustained-release-regimen-with-dual-effects-in-early-intervention-of-tendinopathy
#20
Ming-Yen Hsiao, An-Ci Lin, Wei-Hao Liao, Tyng-Guey Wang, Chia-Hsien Hsu, Wen-Shiang Chen, Feng-Huei Lin
Resulting from accumulative microtrauma, impaired healing and oxidative stress, tendinopathy is a debilitating and relentlessly deteriorating disease that greatly affects daily function and quality of life. Current therapy usually provides symptomatic relief only. Sufferers undergo repetitive and protracted treatment courses that rarely alter the disease process. We aim to develop a sustained-release regimen with an intrinsic therapeutic effect in tendinopathy treatment, using oxidised hyaluronic acid/adipic acid dihydrazide hydrogel (HA hydrogel) as both the drug carrier and a mitigating agent of symptoms...
March 18, 2019: Scientific Reports
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