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Current Molecular Pharmacology

Jasmine Kaur, Abdelkader Daoud, Scott T Eblen
BACKGROUND: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis...
February 14, 2019: Current Molecular Pharmacology
Lingyan Ye, Zheng Cao, Weiwei Wang, Naiming Zhou
BACKGROUND: Cannabinoid has long been used for medicinal purposes. Cannabinoid signaling has been considered the therapeutic targets for treating pain, addiction, obesity, inflammation, and other diseases. Recent studies have suggested that in addition to CB1 and CB2, there are non-CB1 and non-CB2 cannabinoid-related orphan GPCRs including GPR18, GPR55, and GPR119. In addition, CB1 and CB2 display allosteric binding and biased signaling, revealing correlations between biased signaling and functional outcomes...
February 14, 2019: Current Molecular Pharmacology
Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Brijesh K Sutariya, Maulik S Patel, Rajesh H Bahekar, Mukul R Jain
BACKGROUND: Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism...
February 11, 2019: Current Molecular Pharmacology
Elena Taverna, Maida De Bortoli, Elisa Maffioli, Cristina Corno, Silvio Trivulzio, Emilio Ciusani, Arnaldo Pinelli, Gabriella Tedeschi, Paola Perego, Italia Bongarzone
OBJECTIVE: Marycin is a porphyrin-type compound synthetically modified to spontaneously release fluorescence. This study is aimed to understanding possible mechanisms that could account for the antiproliferative effects observed in marycin. A proteomic approach was used to identify the molecular effects. The proteome of proliferating MDA-MB-231 breast cancer cells was compared with that of marycin-treated cells. METHODS: label-free proteomic analysis by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used to reveal changes in protein expression and fluorescence microscopy and flow cytometry were used to detect subcellular organelle dysfunctions...
February 3, 2019: Current Molecular Pharmacology
Anna Boguszewska-Czubara, Jacek Kurzepa, Grażyna Biała, Katarzyna Kaszubska, Karolina Grot, Piotr Tarkowski, Joanna Kowalczyk, Serena Silvestro, Caterina Faggio, Barbara Budzyńska
BACKGROUND: The use of drugs of addiction, as mephedrone, is associated with functional neuronal disorders due to remodeling of the nervous tissue. Key enzymes in remodeling are extracellular matrix (ECM) proteases like matrix metalloproteases (MMPs). Recently, MMPs have been of great interest as some studies point to a fact that the alterations in structural remodeling of synaptic connections modify learning-dependent changes, which remain active even after a prolonged period of abstinence...
January 14, 2019: Current Molecular Pharmacology
Pitchai Balakumar, Nanjaian Mahadevan, Ramanathan Sambathkumar
BACKGROUND: Diabetes mellitus and concomitant dyslipidemia, being referred to as 'diabetic dyslipidemia', are the foremost detrimental factors documented to play a pivotal role in cardiovascular illness. Diabetic dyslipidemia is associated with insulin resistance, high plasma triglyceride levels, low HDL-cholesterol concentration and elevated small dense LDL-cholesterol particles. Maintaining an optimal glucose and lipid levels in patients afflicted with diabetic dyslipidemia could be a major task that might require a well-planned diet-management system and regular physical activity, or otherwise an intake of a combined antidiabetic and antihyperlipidemic medications...
January 11, 2019: Current Molecular Pharmacology
Amit D Kandhare, Zihao Liu, Anwesha A Mukherjee, Subhash L Bodhankar
BACKGROUND: Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response. AIM: To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved. MATERIALS AND METHODS: Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR...
January 1, 2019: Current Molecular Pharmacology
Lisha Xie, Tao Jiang, Ailan Cheng, Ting Zhang, Pin Huan, Pei Li, Gebo Wen, Fanghong Lei, Yun Huang, Xia Tang, Jie Gong, Yunpeng Lin, Jianke Kuai, Weiguo Huang
BACKGROUND: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. METHODS: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines were detected by Western blotting...
December 17, 2018: Current Molecular Pharmacology
Roman A Zinovkin, Andrey A Zamyatnin
BACKGROUND: Targeting of drugs to the subcellular compartments represents one of the modern trends in molecular pharmacology. The approach for targeting mitochondria was developed nearly 50 years ago, but only in the last decade has it started to become widely used for delivering drugs. A number of pathologies are associated with mitochondrial dysfunction, including cardiovascular, neurological, inflammatory and metabolic conditions. OBJECTIVE: This mini-review aims to highlight the role of mitochondria in pathophysiological conditions and diseases, to classify and summarize our knowledge about targeting mitochondria and to review the most important preclinical and clinical data relating to the antioxidant lipophilic cations MitoQ and SkQ1...
November 27, 2018: Current Molecular Pharmacology
Manaf AlMatar, Essam A Makky, Husam AlMandeal, Emel Eker, Begüm Kayar, Işιl Var, Fatih Köksal
BACKGROUND: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity...
November 26, 2018: Current Molecular Pharmacology
Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
BACKGROUND: Natriuretic peptide system (NPS) alterations are involved in pathogenesis of diabetic cardiomyopathy (DCM) and nephropathy (DN), however its epigenetic regulation is still unclear. Interestingly, histone acetylation epigenetically regulates neprilysin expression in Alzheimer's disease. OBJECTIVES: The present study was aimed at delineating role of histone acetylation in regulation of NPS in DCM and DN. METHODS: Streptozotocin (55 mg/kg, i...
November 21, 2018: Current Molecular Pharmacology
Michael Kahn
No abstract text is available yet for this article.
2019: Current Molecular Pharmacology
Shahinda S R Alsayed, Chau Chun Beh, Neil R Foster, Alan D Payne, Yu Yu, Hendra Gunosewoyo
Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercule bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M...
October 25, 2018: Current Molecular Pharmacology
Alexander V Zholos, Olesia F Moroz, Maksim V Storozhuk
BACKGROUND: Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD...
October 12, 2018: Current Molecular Pharmacology
Ricardo Jorge Dinis-Oliveira, Carolina Lanca Pereira, Diana Dias da Silva
BACKGROUND: Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood. OBJECTIVES: This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response...
October 10, 2018: Current Molecular Pharmacology
Keywan Mortezaee, Nasser Hashemi Goradel, Peyman Amini, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Masoud Najafi, Bagher Farhood
BACKGROUND: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy...
October 10, 2018: Current Molecular Pharmacology
Faith A A Kwa, Merrole F Cole-Sinclair, Miroslav K Kapuscinski
BACKGROUND: Treatment of haematological malignancies with conventional DNA-damaging drugs, such as chlorambucil (CLB), commonly results in p53-dependent chemo-resistance. Chromatin modifying agents, such as histone deacetylase inhibitors (HDACIs), sodium butyrate (NaBu) and trichostatin A (TSA), may reverse chemo-resistance by modulating the activity of chromatin remodeling enzymes and/or genes that control cell proliferation, differentiation and survival. OBJECTIVE: This study examined the potential use of HDACIs and CLB combination therapies in an in vitro chemo-resistant leukaemia model...
October 10, 2018: Current Molecular Pharmacology
Maryam Naserian, Elham Ramazani, Mehrdad Iranshahi, Zahra Tayarani-Najaran
BACKGROUND: Besides the first-line medication for the treatment of type 2 diabetes, the growth inhibitory activity of metformin alone or in combination of conventional chemotherapeutics has been addressed on a panel of cell lines. In this study, we investigated the cytotoxicity and apoptosis of the metformin alone and in combination with dacarbazine in Raji and Ramos lymphoma cell lines. METHODS: Cell viability and apoptosis measured using resazurin assay, flow cytometry of PI stained cells and western blot analysis...
August 30, 2018: Current Molecular Pharmacology
Seyede Hadis Momeni Hasan Abadi, Alireza Shirazi, Ali Mohammad Alizadeh, Vahid Changizi, Masoud Najafi, Solmaz Khalighfard
PURPOSE: Radiation causes damage to irradiated tissues and also tissues that do not receive direct irradiation through a phenomenon called bystander effects. Melatonin as a potent antioxidant and anti-inflammatory agent is known for protection of normal tissues against ionizing irradiation. In addition, some studies have suggested that Melatonin may have some anti-cancer properties. Although the complete mechanisms remain unknown, it can act via immunomodulatory effects. The aim of this study was to evaluate the effect of pretreatment with melatonin on oxidative damage caused by direct irradiation and bystander effects on the lung and heart tissue after xenograft mice colon cancer irradiation in Balb/c mice...
August 30, 2018: Current Molecular Pharmacology
Peyman Amini, Hanifeh Mirtavoos-Mahyari, Elahe Motevaseli, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Mohsen Cheki, Bagher Farhood, Rasoul Yahyapour, Alireza Shirazi, Nouraddin Abdi Goushbolagh, Masoud Najafi
BACKGROUND: Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) has been proved. However, in recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products...
August 2, 2018: Current Molecular Pharmacology
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