Antitumor studies. Part 5: Synthesis, antitumor activity, and molecular docking study of 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins

Various novel 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins derivatives have been synthesized by direct coupling of 5-deazaflavins and N-alkyl or aryl amines. The antitumor activities against human tumor cell lines CCRF-HSB-2 and KB cells have been investigated in vitro and many compounds showed promising potential antitumor activities with less cytotoxicities. AutoDock molecular docking into PTK (PDB code: 1t46) has been done for lead optimization of these compounds as potential PTK inhibitors. Some of the synthesized 5-(monosubstituted amino)-2-deoxo-2-phenyl-5-deazaflavins at the 5-position exhibited reasonable binding affinities into PTK with the hydrogen bond through their C(5)-NH moiety.     

The role of microRNAs regulating the expression of matrix metalloproteinases (MMPs) in breast cancer development,progression, and metastasis

MicroRNAs (miRNAs) regulate several biological and physiological processes in mammalian cells, including cellular proliferation, differentiation, apoptosis, and metabolism. Recent studies have confirmed the alteration of them during the cancer development. Matrix metalloproteinases (MMPs), belonging to the large family of proteases, have also been demonstrated to play crucial roles in tissue remodeling, and to support cancer progression and metastasis. There are several known miRNAs which regulate the MMP family and their expression. The expression profiles of miRNAs involved in MMP regulation, change during cancer progression, and metastasis. The present review focuses on important miRNAs capable of targeting MMPs through direct and indirect interactions during the breast cancer development, progression, and metastasis.     

Atorvastatin and losartan may upregulate renalase activity in hypertension but not coronary artery diseases: The role of gene polymorphism

The aim is to explore the treatment effect of coronary artery disease (CAD) and hypertension on plasma levels of renalase activity and also the possible association of renalase rs10887800 gene polymorphism with CAD and hypertension. A total of 286 patients who received coronary angiography were included in the study. Subjects were divided into four groups including (1) hypertensive with no CAD (H-Tens, n = 60); (2) CAD with hypertension (CAD + H-Tens, n = 71); (3) CAD with no hypertension (CAD, n = 61); and (4) nonhypertensive with no CAD as a control group (Con, n = 69). The plasma renalase activity was measured using the Amplex Red Monoamine Oxidase Assay Kit. Renalase rs10887800 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Atorvastatin (P = 0.005), losartan (P < 0.001), and captopril (P = 0.001) were administered significantly more in case groups compared with the Con group. Significant higher and lower levels of renalase activity were observed in H-Tens and CAD patients compared with control subjects (P < 0.001 for both comparisons). Furthermore, no significant differences were obtained in the risk or protective effects of renalase rs10887800 SNP against hypertension and/or CAD in both recessive and dominant genetic models (P > 0.05). According to the findings of the present study, atorvastatin and losartan therapy assumes considerable significance in alleviating hypertension, but not CAD, by increasing the renalase activity. Furthermore, it was found that renalase rs10887800 is less likely a predisposing factor for susceptibility to hypertension and/or CAD in an Iranian southeast population.     

Gap junction blockers: a potential approach to attenuate morphine withdrawal symptoms

Background

The exact mechanisms of morphine-induced dependence and withdrawal symptoms remain unclear. In order to identify an agent that can prevent withdrawal syndrome, many studies have been performed. This study was aimed to evaluate the effect of gap junction blockers; carbenoxolone (CBX) or mefloquine (MFQ); on morphine withdrawal symptoms in male rat.Adult male Wistar rats (225 – 275 g) were selected randomly and divided into 10 groups. All groups underwent stereotaxic surgery and in order to induce dependency, morphine was administered subcutaneously) Sc) at an interval of 12 hours for nine continuous days. On the ninth day of the experiment, animals received vehicle or CBX (100, 400, 600 μg/10 μl/rat, icv) or MFQ (50, 100 and 200 μg/10 μl/rat, icv) after the last saline or morphine (Sc) injection. Morphine withdrawal symptoms were precipitated by naloxone hydrochloride 10 min after the treatments. The withdrawal signs including: jumping, rearing, genital grooming, abdomen writhing, wet dog shake and stool weight, were recorded for 60 minutes.

Results

Results showed that CBX and MFQ decreased all withdrawal signs; and the analysis indicated that they could attenuate the total withdrawal scores significantly.

Conclusion

Taking together it is concluded that gap junction blockers prevented naloxone-precipitated withdrawal symptoms.     

Breast-Feeding Protects Infantile Diarrhea Caused by Intestinal Protozoan Infections

This study investigated the effect of breast-feeding in protection against protozoan infection in infants with persistent diarrhea. Infants were classified into 2 groups; 161 breast-fed infants and the same number of non-breast-fed infants. Microscopic examinations of stool were done for detection of parasites and measuring the intensity of infection. Moreover, serum levels of IgE and TNF-α were measured by ELISA. Cryptosporidium spp., Entamoeba histolytica/Entamoeba dispar, Giardia lamblia, and Blastocystis sp. were demonstrated in infants with persistent diarrhea. The percentage of protozoan infections was significantly lower in breast-fed infants than that in the non-breast-fed infants. The levels of IgE and TNF-α were significantly lower in the breast-fed group than in the non-breast-fed group. There were significant positive associations between the serum levels of IgE and TNF-α and the intensity of parasite infection in the breast-fed group. It is suggested that breast-feeding has an attenuating effect on the rate and intensity of parasite infection.     

Toxoplasma gondii profilin and tachyzoites RH strain may manipulate autophagy via downregulating Atg5 and Atg12 and upregulating Atg7

Molecular Biology Reports - Autophagy process is an important defense mechanism against intracellular infection. This process plays a critical role in limiting the development of Toxoplasma gondii....     

Design of Metasurface-Based Multi-layer THz Filters Utilizing Optimization Algorithm with Distinct Fitness Function Definitions

In this paper, an evolutionary optimization procedure is presented to generate band-pass metasurface-based filters in terahertz regime. As a measure of novelty, pass-band, transition, and out-band characteristics are investigated separately, all of which result in different metasurfaces for filtering applications. The presented approach is defined based on random hill climbing algorithm, regarding the established link between Matlab and HFSS software. A metasurface-based filter with specific properties is considered as the main problem to be solved by the optimization method. Moreover, the fuzzy theory, mean square method, and weighting coefficient procedure are considered to define an efficient fitness function evaluation approach. Also, a step-by-step procedure is used to generate desired structures with a great note of efficiency. The final generated structure has magnificent characteristics including sharp transitions together with transmittance around 0.68 and less than 0.04 at pass-band and out-band regions, respectively. Also, the generated metasurface benefits from wide bandwidth (65%) and great compactness compared to other previous works.

     

Expression profile of lncRNAs and miRNAs in esophageal cancer: Implications in diagnosis,prognosis, and therapeutic response

Esophageal cancer is the seventh most common cancer worldwide. Although a number of environmental and lifestyle-related risk factors have been identified for this kind of cancer, the exact molecular mechanisms of tumor evolution have not been clarified yet. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) as important regulators of gene expression and chromatin configuration have essential roles in the pathogenesis of esophageal cancer. They have been shown to alter the function of cancer-related signaling pathways such as phosphoinositide 3-kinase/protein kinase B and Wnt pathway, thus they might modulate the response of patients to pathway-targeted therapies. Moreover, a number of lncRNAs, such as AFAP1-AS1, UCA1, HOTAIR, LOC285194, and TUSC7, are involved in conferring chemoresistant/radioresistant in esophageal cancer cells. A complex network of interaction exists between lncRNAs and miRNAs in the context of esophageal cancer. Finally, various panels of lncRNAs and miRNAs have been introduced that can predict the survival of esophageal cancer patients. In this review article, we summarize the recent findings regarding the role of miRNAs and lncRNAs in the pathogenesis of esophageal cancer with the special focus on their regulatory roles on signaling pathways, their potential as diagnostic/prognostic markers, and their relevance with therapeutic response.     

Nucleoside diphosphate kinase Nm23-M1 involves in oligodendroglial versus neuronal cell fate decision in vitro

The adult glial progenitor cells were recently shown to be able to produce neurons in central nervous system (CNS) and to become multipotent in vitro. Although the fate decision of glial progenitors was studied extensively, the signals and factors which regulate the timing of neuronal differentiation still remain unknown. To elucidate the mechanisms underlying the neuronal differentiation from glial progenitors, we modified the gene expression profile in NG2⁺ glial progenitor cells using enhanced retroviral mutagen (ERM) technique followed by phenotype screening to identify possible gene(s) responsible for glial-neuronal cell fate determination. Among the identified molecules, we found the gene named non-metastatic cell 1 which encodes a nucleoside diphosphate kinase protein A (Nm23-M1 or NME1). So far, the Nm23 members have been shown to be involved in various molecular processes including tumor metastasis, cell proliferation, differentiation and cell fate determination. In the present study, we provide evidence suggesting the role of NME1 in glial-neuronal cell fate determination in vitro. We showed that NME1 is widely expressed in neuronal structures throughout adult mouse CNS. Our immunohistochemical results revealed that NME1 is strongly colocalized with NF200 through white matter of spinal cord and brain. Interestingly, NME1 overexpression in oligodendrocyte progenitor OLN-93 cells potently induced the acquisition of neuronal fate, while its silencing was shown to promote oligodendrocyte differentiation. Furthermore, we demonstrated that dual-functional role of NME1 is achieved through cAMP-dependent protein kinase (PKA). Our data therefore suggested that NME1 acts as a switcher or reprogramming factor which involves in oligodentrocyte versus neuron cell fate specification in vitro.