Research in Pharmaceutical Sciences

BACKGROUND AND PURPOSE: Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model. EXPERIMENTAL APPROACH: Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for 28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively...

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer in which three hormone receptors are negative. This work aimed at identifying customized potential molecules inhibiting epidermal growth factor receptor (EGFR) by exploring variants using the pharmacogenomics approaches. EXPERIMENTAL APPROACH: The pharmacogenomics approach has been followed to identify the genetic variants across the 1000 genomes continental population...

BACKGROUND AND PURPOSE: Despite the widespread utilization of cancer vaccines with specified antigens, the use of whole tumor cell lysates in tumor immunotherapy would be a very promising approach that can overcome several significant obstacles in vaccine production. Whole tumor cells provide a broad source of tumor-associated antigens and can activate cytotoxic T lymphocytes and CD4+ T helper cells concurrently. On the other hand, as an effective immunotherapy strategy, recent investigations have shown that the multi-targeting of tumor cells with polyclonal antibodies, which are also more effective than monoclonal antibodies at mediating effector functions for target elimination, might minimize the escape variants...

BACKGROUND AND PURPOSE: Peripheral neuropathy is one of the most prevalent and undesirable side effects of taxane-containing chemotherapy regimens. This study aimed to investigate the effect of acetyl-L-carnitine (ALC) on the prevention of taxane-induced neuropathy (TIN). EXPERIMENTAL APPROACH: MEDLINE, PubMed, Cochrane Library, Embase, Web of Science, and Google scholar were systemically applied as electronic databases from 2010 to 2019. The current systematic review was carried out based on the main considerations of PRISMA preferential reporting items for systematic review and meta-analyses...

BACKGROUND AND PURPOSE: Alpha-lipoic acid (ALA) is an antioxidant with radioprotective properties. We designed the current work to assess the neuroprotective function of ALA in the presence of oxidative stress induced by radiation in the brainstem of rats. EXPERIMENTAL APPROACH: Whole-brain radiations (X-rays) was given at a single dose of 25 Gy with or without pretreatment with ALA (200 mg/kg BW). Eighty rats were categorized into four groups: vehicle control (VC), ALA, radiation-only (RAD), and radiation + ALA (RAL)...

BACKGROUND AND PURPOSE: Obesity is a public health problem and the existence of beige adipocytes has got interested as a potential therapeutic involvement for obesity and obesity-associated diseases. Adipose tissue M1 macrophage inhibition, also, has a vital role in obesity via down-regulating adipose tissue inflammation and the use of natural compounds such as oleic acid with exercise has been proposed. The present study aimed to evaluate the possible effects of oleic acid and exercise on diet-induced thermogenesis and obesity in rats...

BACKGROUND AND PURPOSE: Several studies have shown the effectiveness of screening programs in decreasing the costs and disutility of type-2 diabetes and related complications. As there is a growth in the incidence of type-2 diabetes amongst the Iranian population, the cost-effectiveness of performing type-2 diabetes screening tests in community pharmacies of Iran was evaluated in this study from the payer's perspective. The target population consisted of two hypothetical cohorts of 1000 people 40 years of age without a prior diagnosis of diabetes, for the intervention (screening test) and no-screening groups...

BACKGROUND AND PURPOSE: There has not been a comprehensive study on the simultaneous effects of metformin, etoposide, and epirubicin on thyroid cancer cells. Hence, the current research proposed the in vitro study on the effect of metformin alone and in combination with etoposide and epirubicin on the rate of proliferation, apoptosis, necrosis, and migration against B-CPAP and SW-1736 cells as thyroid cancer cell lines. EXPERIMENTAL APPROACH: MTT-based proliferation assay, combination index method, flow cytometry, and scratch wound healing assays were used to evaluate the simultaneous effects of the three approved drugs against thyroid cancer cells...

BACKGROUND AND PURPOSE: Some chemotherapeutic drugs are associated with an increased risk of cardiotoxicity in patients. Protocatechuic acid (PCA) is a phenolic acid with valuable cardiovascular, chemo-preventive, and anticancer activities. Recent studies have shown the cardioprotective effects of PCA in several pathological conditions. This investigation aimed to assess the possible protective effects of PCA on cardiomyocytes against toxicities caused by anti-neoplastic agents, doxorubicin (DOX), and arsenic trioxide (ATO)...

BACKGROUND AND PURPOSE: Recently, the use of immunotoxins for targeted cancer therapy has been proposed, to find new anticancer drugs with high efficacy on tumor cells with minimal side effects on normal cells. we designed and compared several arazyme (AraA)-based fusion proteins with different ligands to choose the best-targeted therapy for interleukin 13 receptor alpha 2 (IL13Rα2)-overexpressed cancer cells. For this purpose, IL13Rα2 was selected as a receptor and IL13 and IL13...

BACKGROUND AND PURPOSE: Azithromycin (AZ) is a macrolide antibiotic that is soluble in saliva pH; its bitter taste can be well sensed, decreasing the ability of the patient to get the drug. Thus, handling such a bitter taste is challenging in developing the oral formulation. A wide range of methods has been applied to tackle this problem. Cubosomes are considered nanoparticles forming cubic three-dimensional structures with a taste-masking effect. This research aimed to apply cubosomes to mask AZ's bitter taste...

BACKGROUND AND PURPOSE: The purpose of the current study was to investigate the protective effects of acute and chronic administration of different doses of vitamin D3 on pentylenetetrazol (PTZ)-induced epileptiform activities in rats. EXPERIMENTAL APPROACH: Sixty Wistar rats in chronic and acute groups were used in this study. In the chronic groups, animals received vitamin D3 at 50, 100, and 150 μg/kg; vitamin D3 (50 μg/kg, i.p.) + diazepam (0.1 mg/kg, i...

BACKGROUND AND PURPOSE: Although some proposed mechanisms responsible for tamoxifen resistance have already been present, further study is needed to determine the mechanisms underlying tamoxifen resistance more clearly. The critical role of Notch signaling has been described in promoting resistance in therapeutics, but there is little information about its role in tamoxifen resistance progression. EXPERIMENTAL APPROACH: In the present study, the expression of Notch pathway genes, including Notch4, nicastrin and the Notch downstream target Hes1 was evaluated using quantitative RT-PCR in 36 tamoxifen-resistant (TAM-R) and 36 tamoxifen-sensitive (TAM-S) patients...

BACKGROUND AND PURPOSE: The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABAB Rs ) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABAB Rs blockade in response to morphine was assessed on the neuronal activity in the LHb...

BACKGROUND AND PURPOSE: Lysosomal-targeted drug delivery can open a new strategy for drug therapy. However, there is currently no universally accepted simulated or artificial lysosomal fluid utilized in the pharmaceutical industry or recognized by the United States Pharmacopeia (USP). EXPERIMENTAL PROCEDURE: We prepared a simulated lysosomal fluid (SLYF) and compared its composition to a commercial artificial counterpart. The developed fluid was used to test the dissolution of a commercial product (Robitussin® ) of a lysosomotropic drug (dextromethorphan) and to investigate in-vitro lysosomal trapping of two model drugs (dextromethorphan and (+/-) chloroquine)...

BACKGROUND AND PURPOSE: Considering various studies implying anticancer activity of the hydrazone and oxamide derivatives through different mechanisms such as kinases and calpain inhibition, herein, we report the synthesis, characterization, and evaluation of the antiproliferative effect of a series of hydrazones bearing oxamide moiety compounds ( 7a-7n ) against a panel of cancer cell lines to explore a novel and promising anticancer agent ( 7k ). EXPERIMENTAL APPROACH: Chemical structures of the synthesized compounds were confirmed by FTIR, 1 H-NMR, 13 C-NMR, and mass spectra...

BACKGROUND AND PURPOSE: Irritable bowel syndrome (IBS) is a disease that shows its impacts on many populations worldwide. It is known as a functional disorder of the gastrointestinal tract followed by diarrhea and fecal inconsistency. Due to the lack of treatment in the allopathic medicine system for IBS, people in the western world use different herbs as alternative medicine. In the present study, we evaluated the dried extract of Dracocephalum kotschyi against IBS. EXPERIMENTAL APPROACH: In a randomized, double-blinded, placebo-controlled clinical trial, 76 diarrhea-predominant IBS patients were randomly assigned to two equal groups: the control group (given the placebo capsule containing 250 mg of dibasic calcium phosphate) and the treatment groups (given the capsule containing 75 mg of the dry extract of D...

BACKGROUND AND PURPOSE: The treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is still a great challenge. This study evaluated the effectiveness of the colistin/levofloxacin regimen compared to the usual colistin/meropenem regimen in the treatment of patients with VAP caused by CRAB. EXPERIMENTAL APPROACH: The patients with VAP were randomly assigned to experimental (n = 26) and control (n = 29) groups...

BACKGROUND AND PURPOSE: Precise structures of macromolecules are important for structure-based drug design. Due to the limited resolution of some structures obtained from X-ray diffraction crystallography, differentiation between the NH and O atoms can be difficult. Sometimes a number of amino acids are missing from the protein structure. In this research, we intend to introduce a small database that we have prepared for providing the corrected 3D structure files of proteins frequently used in structure-based drug design protocols...

BACKGROUND AND PURPOSE: Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medications, have not been reported. The aim of the present study was to identify a new anti-diabetes candidate from secondary metabolite compounds of AP through PDE9 inhibition. EXPERIMENTAL APPROACH: In order to prepare the chemical structures of the secondary metabolites of AP and PDE9, docking and molecular dynamics simulations were run using Discovery Studio Visualizer, AutoDockTools, AutoDock, and Gromacs, along with a few other supporting software packages...