Expression analysis of mTOR-associated lncRNAs in multiple sclerosis

Metabolic Brain Disease - mTOR has been shown to be involved in the regulation of immune responses and differentiation of immune cells. This protein is a candidate molecule for unraveling the...     

Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with 90Y and 111In for domestic radioimmunotherapy and radioscintigraphy of Non-Hodgkin’s Lymphoma

Background

On the basis of results of our previous investigations on ⁹⁰Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin’s Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with ¹¹¹In and ⁹⁰Y was investigated.

Methods

¹¹¹In and ⁹⁰Y with high radiochemical and radionuclide purity were prepared by ¹¹²Cd (p,2n)¹¹¹In nuclear reaction and a locally developed ⁹⁰Sr/⁹⁰Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with ¹¹¹In and ⁹⁰Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation.

Results

The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of ⁹⁰Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone.

Conclusion

Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with ⁹⁰Y and ¹¹¹In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran.     

Linear Friction Welding of an AZ91 Magnesium Alloy and the Effect of Ca Additions on the Weld Characteristics

Solid-state welding offers distinct advantages for joining reactive materials, such as magnesium (Mg) and its alloys. This study investigates the effect of linear friction welding (LFW) on the microstructure and mechanical properties of cast AZ91 (Mg–9Al–1Zn) and AZ91–2Ca alloys, which (to the best knowledge of the authors) has not been reported in the literature. Using the same set of LFW process parameters, similar alloy joints—namely, AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca—were manufactured and found to exhibit integral bonding at the interface without defects, such as porosity, inclusions, and/or cracking. Microstructural examination of the AZ91/AZ91 joint revealed dissolution of the Al-rich second phase in the weld zone, while the Mn containing phases remained and were refined. In the AZ91–2Ca/AZ91–2Ca joint, the weld zone retained Ca- and Mn-rich phases, which were also refined due to the LFW process. In both joint types, extensive recrystallization occurred during LFW, as evidenced by the refinement of the grains from ~1000 µm in the base materials to roughly 2–6 µm in the weld zone. These microstructural changes in the AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca joints increased the hardness in the weld zone by 32%. The use of digital image correlation for strain mapping along the sample gage length during tensile testing revealed that the local strains were about 50% lower in the weld zone relative to the AZ91 and AZ91–2Ca base materials. This points to the higher strength of the weld zone in the AZ91/AZ91 and AZ91–2Ca/AZ91–2Ca joints due to the fine grain size, second phase refinement, and strong basal texture. Final fracture during tensile loading of both joints occurred in the base materials.     

Effects of two dietary exogenous multi-enzyme supplementation,Natuzyme<Superscript>®</Superscript> and beta-mannanase (Hemicell<Superscript>®</Superscript>), on growth and blood parameters of Caspian salmon (<Emphasis Type="Italic">Salmo trutta caspius</Emphasis>)

Recent increases in feed ingredient costs have motivated the fisheries industry to identify technologies that will improve feed utilisation and reduce the cost per pound of gain. The effects of two supplemental exogenous enzymes (Natuzyme® and Hemicell®) on the growth performance in Caspian salmon (Salmo trutta caspius) were examined over an 8-week feeding trial. After the experimental period, the survival rate ranged from 91.33?±?1.15 % in controls to 96.67?±?1.15 % in the group that received 0.5 g Natuzyme® kg^?1?+?0.5 g Hemicell® kg^?1 (NH) in their diet and there was a statistical difference between experimental and control groups (p?<?0.05). Growth rate was significantly higher in the NH group (1.01?±?0.01) than the other groups (Sig.?=?0.00). The best feed conversion rate (0.64?±?0.01) was in the NH group and it was significantly lower than the control group, the 0.5 g Natuzyme® kg^?1 group, and the 0.25 g Hemicell® kg^?1 group (Sig.?=?0.03). The best final body weight (80.68?±?5.27) was observed in the NH group. Also, WBC count (7,716.67?±?348.80 N/mm³) was significantly higher in the NH group compared to the control (6,916.67?±?194.10 N/mm³; p?<?0.05). No difference was observed in haematocrit%, haemoglobin, red blood cell, mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration (p?>?0.05). The results suggested that enzyme supplementation caused significant improvement on growth performance and feed utilisation in Caspian salmon.     

In vivo characterization of emerging white matter microstructure in the fetal brain in the third trimester

The third trimester of pregnancy is a period of rapid development of fiber bundles in the fetal white matter. Using a recently developed motion‐tracked slice‐to‐volume registration (MT‐SVR) method, we aimed to quantify tract‐specific developmental changes in apparent diffusion coefficient (ADC), fractional anisotropy (FA), and volume in third trimester healthy fetuses. To this end, we reconstructed diffusion tensor images from motion corrected fetal diffusion magnetic resonance imaging data. With an approved protocol, fetal MRI exams were performed on healthy pregnant women at 3 Tesla and included multiple (2–8) diffusion scans of the fetal head (1–2 b = 0 s/mm² images and 12 diffusion‐sensitized images at b = 500 s/mm²). Diffusion data from 32 fetuses (13 females) with median gestational age (GA) of 33 weeks 4 days were processed with MT‐SVR and deterministic tractography seeded by regions of interest corresponding to 12 major fiber tracts. Multivariable regression analysis was used to evaluate the association of GA with volume, FA, and ADC for each tract. For all tracts, the volume and FA increased, and the ADC decreased with GA. Associations reached statistical significance for: FA and ADC of the forceps major; volume and ADC for the forceps minor; FA, ADC, and volume for the cingulum; ADC, FA, and volume for the uncinate fasciculi; ADC of the inferior fronto‐occipital fasciculi, ADC of the inferior longitudinal fasciculi; and FA and ADC for the corticospinal tracts. These quantitative results demonstrate the complex pattern and rates of tract‐specific, GA‐related microstructural changes of the developing white matter in human fetal brain.     

Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats

BACKGROUND AND PURPOSE: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. KEY RESULTS: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB(1) antagonist) or capsazepine (vanilloid VR(1) antagonist), but not AM630 (CB(2) antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. CONCLUSIONS AND IMPLICATIONS: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB(1) and vanilloid VR(1) receptors.     

Lysosome and HER3 (ErbB3) selective anticancer agent kahalalide F: semisynthetic modifications and antifungal lead-exploration studies

Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.     

HLA-DRBeta1, circulating Th1/Th2 cytokines and immunological homunculus in coronary atherosclerosis

Coronary atherosclerotic disease is one of the most endangering health disorder worldwide. This study was designed to investigate the correlation between HLA-DR1 alleles and circulating Th1/Th2 type cytokines in coronary atherosclerosis. By Elisa, Th1/Th2 type cytokines were determined in serum samples of 31 subjects with unstable angina, 27 subjects with chronic stable angina and 24 individuals as normal control. By SSP-PCR, more than 100 alleles of HLA-DRBeta1 were typed in 24 subjects who had skewed serum levels of Th1/Th2 type cytokines. Lipid profiles were determined by the routine methods of clinical laboratory in all subjects. The mean serum concentration of IL-10 in normal control subjects was higher in comparison to the patient groups.0.33±0.59 pg/ml versus 0.064±0.3 pg/ml in unstable angina pectoris group (p<0.028) and 0.22±0.6 pg/ml in chronic stable subjects. There was no statistically significant difference among the groups in serum levels of other desired cytokines (IFN-Gamma, IL-4). 33.33% of normal control subjects were HLA-DR16 positive whereas none of the subjects with chronic stable angina or individuals with unstable angina pectoris was positive for this antigen. The mean concentration of serum LDL-cholesterol in normal control group was high 142.046±35.40 (pg/ml).This preliminary study shows that the atherogenic effect of the LDL- cholesterol may be dampened by HDL-cholesterol through anti inflammatory cytokine IL-10 and HLA-DR16, a phenomenon interpretable via immunological homunculus theory.