Levels of formaldehyde in residential indoor air of Gonabad,Iran

Abstract

Human health has been identified to be affected more significantly by indoor air quality. Among numerous pollutants present in indoor air, formaldehyde (FA) is of great concern because of its highly hazardous nature. The concentrations of FA were determined from 20 newly decorated homes in the city of Gonabad, Iran during 2015. It was found that the indoor air levels of FA in all the sampled houses were exceptionally high in the range of 21 to 360 µg/m³ (mean of 149.3 µg/m³). If the 24-h average concentrations of FA measured from those sites were concerned, nearly 40% of them were seen to exceed the WHO guideline values (i.e., 100 µg/m³). One of the important reasons for the high concentrations could be low air exchange rates in those houses (e.g., from 0.18 to 0.37?h^?1), high levels of humidity in the newly decorating houses and stronger sources in the indoor environment. Furthermore, its pollution in homes with natural ventilation was seen to be much higher than those of mechanical ventilation. Due to high levels of indoor FA, more effective control procedures should be developed and employed to reduce the risk associated with formaldehyde exposure.     

Effect of alkylation with N-methyl-N-nitrosourea and N-ethyl-N-nitrosourea on the secondary structure of DNA

We have earlier reported that alkylation of DNA by the chemical carcinogen dimethyl sulphate, which mainly alkylates N-7 of guanine and N-3 of adenine, causes the formation of partially denatured regions in double-stranded DNA (Rizvi RY, Alvi NK & Hadi SM, Biosci. Rep. 2, 315-322, 1982). It is known that the major site of alkylation in DNA by N-ethyl-N-nitrosourea (EtNu) are the phosphate groups. N-methyl-N-nitrosourea (MeNu), on the other hand, causes the alkylation of mainly guanine residues. We have therefore studied the effect of these two alkylating carcinogens on the secondary structure of DNA. DNA alkylated with increasing concentrations of EtNu and MeNu was subjected to alkaline and S1 nuclease hydrolysis. Thermal melting profiles of alkylated DNA were also determined using S1 nuclease. The results indicated that alkylation by the two alkylating agents had a differential effect on the secondary structure of DNA. EtNu-alkylated DNA was found to be more thermostable than native DNA at neutral pH. It was however more alkali-labile than MeNu-alkylated DNA. The greater stability of EtNu-alkylated DNA was considered to be due to abolition of negative charges on phosphate alkylation.     

The effect of redox signaling on extracellular matrix changes in diabetic wounds leading to amputation

Introduction& Objectives: Redox signaling is a critical regulator in the process of wound healing. This signaling pathway can be effective in the development or healing of diabetic ulcers through the ECM.In this study, the structure of extracellular matrix investigated in relation to redox signaling in the tissue of patients with diabetic ulcers that lead to organ amputation.Materials and methodsThe case-control design on diabetic patients ulcers as case group and non-diabetic limb ischemia as control were used.Hematoxylin-eosin, trichrome, and elastin staining methods were used for pathological evaluations of ECM. MDA, total thiol, and SOD levels were measured using ELISA kits to assess the oxidative stress level. Also, NO level was measured by using ELISA kits in both groups. Expression levels of genes MMP2, MMP9, and HIF were detected using real-time PCR with SYBR-green assay.ResultsThe pathological results showed an increase in the thickness of collagen and elastin fibers. Lipids atrophy was visible in the tissue isolated from the diabetic wound group. The amount of MAD to evaluate the level of lipid oxidation in patients with diabetic Ulcer was significantly higher than the control group(p < 0.01). Thiol level was significantly lower in the diabetic ulcer group than in the control group(p < 0.0001). The expression of metalloproteinases 2 and 9 genes in the tissues isolated from diabetic ulcers was lower than the control group(p < 0.0001). While the expression of the HIF gene in this group was higher than the control group(p < 0.0001).ConclutionIn the diabetic wound, the HIF secretion due to hypoxic conditions is beneficial for matrix deposition and prevents protease activity, but if the hypoxia persists, it can lead to ECM deposition subsequently increases the tissue pressure, increases of the collagen I-to-collagen III ratio in collagen accumulation that due to more hypoxia , lipidsAtrophy and eventually amputation.     

Oleanolic acid increases the anticancer potency of doxorubicin in pancreatic cancer cells

Combination therapy is a novel cancer therapy approach that combines two or more chemotherapy drugs. This treatment modality enhances the efficacy of chemotherapy by targeting key pathways in an additive or synergistic manner. Therefore, we investigated the efficacy of combination therapy by widely used chemotherapy drug doxorubicin (DOX) and oleanolic acid (OA) to induction of apoptosis for pancreatic cancer (PC) therapy. The effects of DOX, OA, and their combination (DOX-OA) were investigated on proliferation and viability of PC cell line (PANC-1) by MTT assay. Moreover, migration and invasion of the cancer cells were evaluated by trans-well migration assay and wound healing assay. Flow cytometry and DAPI (4′,6-diamidino-2-phenylindole) staining were employed to investigate apoptosis quantification and qualification of the treated cancer cells. Finally, mRNA expression of apoptosis-related genes was assessed by quantitative real-time polymerase chain reaction. Our results demonstrated that the proliferation and metastasis potential of PC cells significantly decreased after treatment by DOX, OA, and DOX-OA. Moreover, we observed an increase in apoptosis percentage in the treated cancer cells. The apoptosis-related gene expression was modified to increase the apoptosis rate in all of the treatment groups. However, the anticancer potency of DOX-OA combination was significantly more than that of DOX and OA treatments alone. Our study suggested that DOX-OA combination exerts more profound anticancer effects against PC cell lines than DOX or OA monotherapy. This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.     

Key biomarkers in cerebral arteriovenous malformations: Updated review

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well-known that metalloproteinase-9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras-mitogen-activated protein kinase-extracellular signal-regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin-6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient-specific risk estimation and improving treatment choices.     

Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model

Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant.     

Benefit of nicorandil using an immunologic murine model of experimental colitis

Inflammatory bowel disease (IBD) is a chronic inflammatory condition with an unknown etiology. Nicorandil, a potassium channel opener, has been used for many years for the treatment of angina. Recently, it has been shown that nicorandil possesses some novel traits such as anti-apoptotic, gastroprotective, free radical scavenging, and anti-inflammatory properties. Therefore, we set out to examine the possible beneficial effect of nicorandil in a rat model of IBD. Colitis was induced by rectal administration of 2,4,6-trintrobenzene sulphonic acid (TNBS) into rats. Groups of animals used in this study were sham, control, and exposure to dexamethasone, nicorandil, glibenclamid (a pure adenosine triphosphate sensitive potassium channel (KATP) blocker), or nicorandil plus glibenclamid. Drugs were administered by gavage and animals were sacrificed after 7 days. Biochemical markers, including TNF-α and IL-1β, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS), were measured in the homogenate of colonic tissue. Results indicate that nicorandil significantly reduces macroscopic and histological damage induced by TNBS. Nicorandil diminishes MPO activity and levels of TBARS, TNF-∢, and IL-1β in damaged colonic tissue with a concomitant increase in FRAP value (P<0.01). These effects were not reversed by coadministration of glibenclamide. In conclusion, nicorandil is able to ameliorate experimental IBD with a dose in which it does not show any anti-hypertensive effect, and the mechanism of which is partially or totally independent from KATP channels. It is hypothesized that nitric oxide donation and free-radical scavenging properties of nicorandil upregulate endothelial nitric oxide synthase may be responsible for this phenomenon. These findings suggest that nicorandil can be useful in treatment of IBD, although further investigations are needed to elucidate the mechanisms involved.