Oncolytic adenovirus: A tool for cancer therapy in combination with other therapeutic approaches

Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue- or tumor-specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach.     

IL-4 down-regulates anaphylatoxin receptors in monocytes and dendritic cells and impairs anaphylatoxin-induced migration in vivo

Anaphylatoxins mobilize leukocytes to the sites of inflammation. In the present study we investigated the impact of GM-CSF, IL-4, and IFN-gamma on anaphylatoxin receptor expression in monocytes and dendritic cells (DC). IL-4 was identified as the strongest down-regulator of the receptors for C5a and C3a in monocytes and monocyte-derived DC (MoDC). To study the impact of IL-4 on anaphylatoxin-induced chemotaxis, an in vivo migration model was established. For this purpose, human monocytes and MoDC were injected i.v. into SCID mice that at the same time received anaphylatoxins into the peritoneal cavity. A peritoneal influx of human monocytes could be demonstrated by 4 h after injections of C5a and C3a. In line with receptor down-regulation, IL-4 treatment inhibited in vivo mobilization of human monocytes and MoDC in response to C5a and C3a. In addition to its effects on human cells, IL-4 reduced C5a receptors in murine bone marrow-derived DC and impaired recruitment of labeled bone marrow-derived DC in syngeneic BALB/c mice to i.p. injected C5a. Overall, these data suggest that inhibition of a rapid anaphylatoxin-induced mobilization of monocytes and DC to inflamed tissues represents an important anti-inflammatory activity of the Th2 cytokine IL-4.     

The effect of VDR gene polymorphisms and vitamin D level on blood pressure,risk of preeclampsia,gestational age,and body mass index

We investigated the influence of vitamin D receptor (VDR) polymorphisms and vitamin D level on the blood pressure and the risk of preeclampsia. In a case-control study, 200 pregnant women, including 100 individuals with preeclampsia along with 100 healthy pregnant women, were studied for VDR FokI, TaqI, and BmsI polymorphisms and serum 25 (OH)-D level using polymerase chain reaction-restriction fragment length polymorphism method and commercial kit, respectively. The mean level of 25 (OH)-D in preeclamptic patients was significantly lower (16.6 ± 4.2 ng/mL, P < 0.001) compared with controls (19.6 ± 3.8 ng/mL). Among all women, a significantly higher systolic blood pressure and before-pregnancy body mass index and also lower gestational age were observed in the presence of 25 (OH)-D level < 20 ng/mL compared with the 20 to 30 ng/mL. A significantly higher frequency of VDR FokI C allele in preeclamptic patients (83%) than controls (74%) was associated with a 1.72-fold increased risk of preeclampsia. In all the studied individuals, the systolic and diastolic blood pressures were significantly higher in the presence of the FokI CC genotype compared with the TC and TT+TC genotypes. Neither VDR Taq1 nor VDR BmsI was associated with the risk of preeclampsia. The haplotype FokI C, TaqI C and BmsI A (CCA) compared with haplotype CTG increased the risk of preeclampsia by 1.4-fold (P = 0.33). Our study suggests an association between VDR FokI polymorphism and an insufficient serum level of 25 (OH)-D with the risk of preeclampsia and also the influence of insufficient 25 (OH)-D level and VDR FokI polymorphism on maternal factors, including blood pressure.     

Synthesis of new ultrasonic-assisted palladium oxide nanoparticles: an in vitro evaluation on cytotoxicity and DNA/BSA binding properties

Abstract

Better solubility and improved toxicity of palladium complexes compared with cisplatin were major reasons for synthesis of novel Pd(II) complex, [Pd(8Q)(bpy)]NO₃ (8Q=8-hydroxyquinolinate, bpy=2,2′-bipyridine). Interaction between the [Pd(8Q)(bpy)]NO₃ complex and calf thymus DNA in aqueous solution has been investigated by circular dichroism (CD), UV-Visible absorption and fluorescence spectroscopic techniques. These experiments showed that prepared Pd(II) complex can effectively intercalate into CT-DNA and weakly bind to BSA in which the bovine serum albumin molecule was unfolded slightly. The cytotoxicity of the prepared complex has been evaluated on the MCF-7 and DU145 cell lines by MTT and TUNEL assay. The MTT results were showed that in DU145, the CC₅₀ values of [Pd(8Q)(bpy)]NO₃ and cisplatin are very close together (10.4 and 8.3?μM, respectively), unlike MCF-7. Accordingly, TUNEL assay was performed on DU145 and apoptosis was clearly obvious by 43% DNA fragmentation in the treated cell lines. So, we can suggest the [Pd(8Q)(bpy)]NO₃ as alternative drug for cisplatin in the future which has great potential in DNA denaturation and apoptosis specially on prostate cancer. PdO nanoparticles were successfully prepared without supported any surfactants via sonochemical approach. The synthesized PdONPs were characterized using UV-Vis and FTIR spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Communicated by Ramaswamy H. Sarma     

COVID-19 under spotlight: A close look at the origin,transmission, diagnosis,and treatment of the 2019-nCoV disease

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.     

Mitochondrial DNA 4977-bp deletion in endometriosis

Endometriosis is a multifactorial gynecological condition characterized by the presence of ectopic endometrial and stromal tissue outside the uterus. Free radicals and Oxidative stress have been proposed to be involved in the pathogenesis of the endometriosis. It has been shown that mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutations due to the high rate of reactive oxygen species production and limited DNA repair capacity in mitochondria. While a number of deletions can occur, the most commonly studied in human is a 4977-bp deletion that removes all or parts of the genes for NADH dehydrogenase subunits 3, 4, 4L and 5, cytochrome C oxidase subunit III and ATP synthase subunits 6 and 8.” We evaluated whether mtDNA common deletion is related with the susceptibility to endometriosis in northern Iran. In this study 80 endometriosis cases and 100 controls were enrolled. Total DNA was extracted from endometrial tissue samples. The mitochondrial common deletion was determined by Gap- polymerase chain reaction (Gap-PCR). It was found that the mitochondrial common deletion was more likely to be present in patients with endometriosis. Assessing indicate that 60 % of patients and 8 % of controls show mtDNA 4977-bp deletion (Odds Ratio [OR] = 17.25, P < 0.0001, confidence interval [CI] = 5.18–57.36). The mtDNA 4977 deletion may play a role in endometriosis. Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.     

Migrasomes and exosomes; different types of messaging vesicles in podocytes

Podocytes, highly specified kidney epithelial cells, live under several pathological stimuli and stresses during which they adapt themselves to keep homeostasis. Nevertheless, under extreme stress, a complex scenario of podocyte damage and its consequences occur. Podocyte damage causes foot process effacement and their detachment from the glomerular basement membrane, leading to proteinuria. Podocyte-derived extracellular vesicles (pEVs), mainly microparticles and exosomes are considered as signaling mediators of intercellular communication. Recently, it has been shown that throughout the injury-related migration procedure, podocytes are capable of releasing the injury-related migrasomes. Evidence indicates that at the early stages of glomerular disorders, increased levels of pEVs are observed in urine. At the early stage of nephropathy, pEVs especially migrasomes seem to be more sensitive and reliable indicators of podocyte stress and/or damage than proteinuria. This review highlights the current knowledge of pEVs and their values for the diagnosis of different kidney diseases.     

Thymidylate synthase and methionine synthase polymorphisms are not associated with susceptibility to childhood acute lymphoblastic leukemia in Kurdish population from Western Iran

In order to determine the influence of polymorphism in thymidylate synthase (TS 28-bp repeat) and methionine synthase (MS A2756G) genes on the susceptibility to acute lymphoblastic leukemia (ALL), 73 children with ALL and 128 age and sex matched unrelated healthy individuals from the Kermanshah Province of Iran were screened. The genotyping of TS 28-bp repeat and MS A2756G polymorphisms were performed by polymerase chain reaction (PCR) and PCR–RFLP, respectively. The frequency of TS 2R allele in patients and controls were 41.5 and 38%, respectively (Odds ratios (OR) = 1.13, 95%CI 0.73–1.74, P = 0.56). The allelic frequency of G allele of MS was higher (25%) in patients compared with healthy subjects (23%) (OR = 1.09, 95%CI 0.67–1.75, P = 0.71). Considering MS AA and TS 3R3R genotypes as reference indicated that individuals with MS GG + TS 2R2R genotypes have 1.3-fold increase in the risk of ALL (OR = 1.3, 95%CI 0.6–2.7, P = 0.5). Our results showed that neither TS 28-bp repeat nor MS A2756G polymorphisms are risk factors for susceptibility to ALL in Western Iran.     

Pollen morphology of Stachys (Lamiaceae) in Iran and its systematic implication

Pollen grains of 30 taxa of the genus Stachys (29 spp. and one subsp.), representing 9 of the currently recognized sections and 1 species of the closely related genus Sideritis (Si. montana) distributed in Iran were examined by light and scanning electron microscopy. Twenty-eight taxa are studied for the first time under aspects of pollen morphology. The basic shape of the pollen grains in most taxa studied is prolate-spheroidal, but subprolate, spheroidal and oblate-spheroidal pollen grains can also be found in few species. The grains are usually tricolpate (the amb triangular), but also tetracolpate (the amb circular to more or less square) in some species (S. iberica, S. atherocalyx and Si. montana). The surface is microreticulate (the frequent type), reticulate, perforate, foveolate-psilate or foveolate. The lumina are separated by smooth or sinuate muri which make them polygonal, more or less rounded and elongate. Major pollen morphological features of the taxa studied are compared and discussed on the basis of taxonomical concepts. In some cases, these characters are useful in delimitation of formerly introduced sections while they mostly provide further characters in separating related species from each other. For example, all members of S. sect. Aucheriana are characterized by elongated lumina. Based on the oblate-spheroidal shape of its pollen as well as tetracolpate aperture type, the results of the present study confirm sect. Pontostachys as including S. angustifolia, S. iberica, S. sparsipilosa as well as S. atherocalyx. Our results also suggest that although some species like S. fruticolosa and S. lavandulifolia are morphologically well characterized, they cannot be separated from other species of Stachys based on pollen morphology.     

Aptamer-based electrochemical biosensor by using Au-Pt nanoparticles,carbon nanotubes and acriflavine platform

Herein, an ultrasensitive electrochemical aptasensor for quantitative detection of bisphenol A (BPA) was fabricated based on a novel signal amplification strategy. This aptasensor was developed by electrodeposition of gold-platinum nanoparticles (Au-PtNPs) on glassy carbon (GC) electrode modified with acid-oxidized carbon nanotubes (CNTs-COOH). In this protocol, acriflavine (ACF) was covalently immobilized at the surface of glassy carbon electrode modified with Au-PtNPs/CNTs-COOH nanocomposite. Attachment of BPA-aptamer at the surface of modified electrode was performed through the formation of phosphoramidate bonds between the amino group of ACF and phosphate group of the aptamer at 5′end. By interaction of BPA with the aptamer, the conformational of aptamer was changed which lead to retarding the interfacial electron transfer of ACF as a probe. Sensitive quantitative detection of BPA was carried out by monitoring the decrease of differential pulse voltammetric (DPV) responses of ACF peak current with increasing the BPA concentration. The resultant aptasensor exhibited good specificity, stability and reproducibility, indicating that the present strategy was promising for broad potential application.