The roles of moonlight ribosomal proteins in the development of human cancers

“Moonlighting protein” is a term used to define a single protein with multiple functions and different activities that are not derived from gene fusions, multiple RNA splicing, or the proteolytic activity of promiscuous enzymes. Different proteinous constituents of ribosomes have been shown to have important moonlighting extra-ribosomal functions. In this review, we introduce the impact of key moonlight ribosomal proteins and dependent signal transduction in the initiation and progression of various cancers. As a future perspective, the potential role of these moonlight ribosomal proteins in the diagnosis, prognosis, and development of novel strategies to improve the efficacy of therapies for human cancers has been suggested.     

Copper (II) complexes with N,S donor pyrazole-based ligands as anticancer agents

BioMetals - A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(PzMe2)], Na[RNCS(PzMe3)], Na[RNCS(PzPhMe)], Na[RNCS(PzPh2)], where...     

Leukemia-derived exosomes: Bringing oncogenic signals to blood cells

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.     

Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK

Current evidence points to renin-angiotensin system as a key mediator in ischemia-reperfusion injury. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, has recently been shown to confer cardioprotection against ischemia-reperfusion in animal models. We sought to examine the expression of ANG II receptors during PPAR-gamma-mediated cardioprotection. Male Sprague-Dawley rats (nondiabetic) were fed either regular rat chow (control diet group, n = 9) or rosiglitazone-rich diet (rosiglitazone-rich diet group, n = 9) and were subjected to 1 h of myocardial ischemia followed by 1 h of reperfusion. A third group of rats had only thoracotomy and pericardiotomy and served as a sham control group (n = 9). Hemodynamics, infarct size, and expression of ANG II type 1 and type 2 receptors (AT1 and AT2) were measured in all groups. There was a 58% reduction of infarct size in the rosiglitazone-rich diet group (P < 0.01 vs. control diet group). Increased myocardial expression of AT(1) receptors in the ischemic-reperfused myocardium was attenuated in the rosiglitazone-rich diet group (P < 0.05 vs. control diet group). Importantly, myocardial AT2 mRNA and protein expression were significantly increased (by >100-fold) in the rosiglitazone-rich diet group (P < 0.05). These changes were accompanied by inhibition of p42/44 MAPK in the rosiglitazone-rich diet group, while the Akt1 expression, believed to mediate insulin sensitization, remained similar in all three groups. The cardioprotective effects of rosiglitazone against myocardial ischemia-reperfusion injury are independent of its insulin-sensitizing properties and are associated with significant overexpression of AT2 receptors along with inhibition of p42/44 MAPK.     

Cancer Visibility among Iranian Familial Networks: To What Extent Can We Rely on Family History Reports?

Objective

Patients’ unawareness of their cancer diagnosis (PUAW) and their tendency for non-disclosure (TTND) to relatives leads to a lack of cancer visibility among familial networks. Lack of familial cancer visibility could affect the accuracy of family cancer history (FCH) reports. In this study, we investigated familial cancer visibility and its potential determinants.

Patients and Methods

A sample of patients with a confirmed cancer diagnosis was interviewed. Participants were asked about their number of relatives, number of their relatives who are aware about the cancer diagnosis, and the number of relatives from whom they intended to conceal their diagnosis. PUAW was also assessed. Point estimates and 95% confidence intervals were calculated using the bootstrap technique. Multivariate analyses were conducted using mixed Poisson and logistic regression analyses.

Results

A total of 415 participants with a mean age of 53±15 years and a male to female ratio of 0.53 were enrolled in this study. The rates of PUAW, TTND, and familial cancer visibility in the total sample were 0.20 (95% confidence interval (CI): 0.16, 0.24), 0.16 (95% CI: 0.12, 0.19), and 0.86 (95% CI: 0.83, 0.89), respectively. PUAW (adjusted rate ratio (RR) = 1.32, 95% CI: 1.27, 1.38), TTND (RR = 0.92, 95% CI: 0.91, 0.93), and the patients’ gender (RR = 0.92, 95% CI: 0.82, 0.95) were the most important determinants of familial cancer visibility.

Conclusion

Familial cancer visibility may be a point of concern among the Iranian population. Self-reported cancer histories and FCHs may have low sensitivities (not exceeding 80% and 86%, respectively) in this population. However, these estimates may vary across different societies, because of societal and cultural contexts.     

Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction

Diabetes is a major risk factor for atherosclerosis. Atherogenesis involves endothelial dysfunction, activation and injury, inflammation, and smooth muscle cell migration and proliferation. Platelet activation in the narrowed arteries is the most proximate event in the culmination of an acute event such as acute myocardial infraction and stroke. Hyperglycemia is associated with all these adverse events in the process of genesis of atherosclerosis. The effect of diabetes (hyperglycemia) is mediated in large part by the state of enhanced oxidative stress, which is not counter-balanced by endogenous antioxidants. This paper reviews the ignition of oxidative stress in diabetes and the mediation of events leading to atherogenesis.     

Human Gongylonema infection in Iran

The first human infection with Gongylonema in Iran is reported in a 35-year-old Iranian woman with complaints of one year duration and treated as a psychotic patient. Two worms, a male, and a female, were retrieved, described, and identified as G. pulchrum based on their morphological characteristics.     

Clavulanic Acid Attenuating Effect on the Diabetic Neuropathic Pain in Rats

Neurochemical Research - Diabetic neuropathy is one of the most common complications of diabetes mellitus. Excess glutamate release and oxidative stress are hypothesized to be involved in the...     

Isolation and characterization of a novel scFv antibody fragments specific for Hsp70 as a tumor biomarker

Many studies have shown that more than 50% of tumors express heat shock protein 70 kDa (Hsp70) at the plasma membrane surface while not seen in normal cells, therefore it is a promising therapeutic target in human cancers. Hence, we used phage display technology to produce a single-chain fragment variable (scFv) antibody against human Hsp70. For this, a target peptide from human Hsp70 was designed using bioinformatics studies and was chemically synthesized. Then, the selection was performed using four rounds of biopanning with a stepwise decreased amount of the target peptide. Fourteen positive scFv clones were selected using monoclonal phage enzyme-linked immunosorbent assay screening, which was further characterized by means of the polymerase chain reaction and DNA sequencing. Among them, the G6 clone was selected to express scFv into the Escherichia coli. Expression and purification of the scFv shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western blot analysis. In silico analysis confirmed specific binding of the scFv to Hsp70 in CDR regions. The specificity of the scFv measured by surface plasmon resonance and immunofluorescence of the A549 human lung carcinoma cell line confirmed the in vitro function of the scFv. Based upon these findings, we propose a novel anti-human Hsp70 scFv as potential immunotherapy agents that may be translated into preclinical/clinical applications.