Enhanced Inflammatory Potential of CD4+ T-Cells That Lack Proteasome Immunosubunit Expression,in a T-Cell Transfer-Based Colitis Model

Proteasomes play a fundamental role in intracellular protein degradation and therewith regulate a variety of cellular processes. Exposure of cells to (pro)inflammatory cytokines upregulates the expression of three inducible catalytic proteasome subunits, the immunosubunits, which incorporate into newly assembled proteasome complexes and alter the catalytic activity of the cellular proteasome population. Single gene-deficient mice lacking one of the three immunosubunits are resistant to dextran sulfate sodium (DSS)-induced colitis development and, likewise, inhibition of one single immunosubunit protects mice against the development of DSS-induced colitis. The observed diminished disease susceptibility has been attributed to altered cytokine production and CD4⁺ T-cell differentiation in the absence of immunosubunits. To further test whether the catalytic activity conferred by immunosubunits plays an essential role in CD4⁺ T-cell function and to distinguish between the role of immunosubunits in effector T-cells versus inflamed tissue, we used a T-cell transfer-induced colitis model. Naïve wt or immunosubunit-deficient CD4⁺ T-cells were adoptively transferred into RAG1^−/− and immunosubunit-deficient RAG1^−/− mice and colitis development was determined six weeks later. While immunosubunit expression in recipient mice had no effect on colitis development, transferred immunosubunit-deficient T- cells were more potent in inducing colitis and produced more proinflammatory IL17 than wt T-cells. Taken together, our data show that modifications in proteasome-mediated proteolysis in T-cells, conferred by lack of immunosubunit incorporation, do not attenuate but enhance CD4⁺ T-cell-induced inflammation.     

Polymer optoelectronic structures for retinal prosthesis

This commentary highlights the effectiveness of optoelectronic properties of polymer semiconductors based on recent results emerging from our laboratory, where these materials are explored as artificial receptors for interfacing with the visual systems. Organic semiconductors based polymer layers in contact with physiological media exhibit interesting photophysical features, which mimic certain natural photoreceptors, including those in the retina. The availability of such optoelectronic materials opens up a gateway to utilize these structures as neuronal interfaces for stimulating retinal ganglion cells. In a recently reported work entitled “A polymer optoelectronic interface provides visual cues to a blind retina,” we utilized a specific configuration of a polymer semiconductor device structure to elicit neuronal activity in a blind retina upon photoexcitation. The elicited neuronal signals were found to have several features that followed the optoelectronic response of the polymer film. More importantly, the polymer-induced retinal response resembled the natural response of the retina to photoexcitation. These observations open up a promising material alternative for artificial retina applications.     

The Effects of Chromium Histidinate on Mineral Status of Serum and Tissue in Fat-Fed and Streptozotocin-Treated Type II Diabetic Rats

The present study was conducted to investigate the effects of chromium histidinate (CrHis) against experimentally induced type II diabetes and on chromium (Cr), zinc (Zn), selenium (Se), manganese (Mn), iron (Fe), and copper (Cu) in serum, liver, and kidney of diabetic rats. The male Wistar rats (n = 60, 8 weeks old) were divided into four groups. Group I received a standard diet (12% of calories as fat); group II were fed standard diet and received CrHis (110 mcg CrHis/kg body weight per day); group III received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg i.p.; HFD/STZ); group IV were treated as group III (HFD/STZ) but supplemented with 110 mcg CrHis/kg body weight per day. The mineral concentrations in the serum and tissue were determined by atomic absorption spectrometry. Compared to the HFD/STZ group, CrHis significantly increased body weight and reduced blood glucose in diabetic rats (p < 0.001). Concentrations of Cr, Zn, Se, and Mn in serum, liver, and kidney of the diabetic rats were significantly lower than in the control rats (p < 0.0001). In contrast, higher Fe and Cu levels were found in serum and tissues from diabetic versus the non-diabetic rats (p < 0.001). Chromium histidinate supplementation increased serum, liver, and kidney concentrations of Cr and Zn both in diabetic and non-diabetic rats (p < 0.001). Chromium supplementation increased Mn and Se levels in diabetic rats (p < 0.001); however, it decreased Cu levels in STZ-treated group (p < 0.001). Chromium histidinate supplementation did not affect Fe levels in both groups (p > 0.05). The results of the present study conclude that supplementing Cr to the diet of diabetic rats influences serum and tissue Cr, Zn, Se, Mn, and Cu concentrations.     

Comparative In Vivo Evaluations of Curcumin and Its Analog Difluorinated Curcumin Against Cisplatin-Induced Nephrotoxicity

Curcumin, a polyphenol, has pharmacological effects including antioxidant, anti-inflammatory and anti-cancer features. In this study, we have performed comparative in vivo evaluations of CDF (curcumin difluorinated) and curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) Control; (2) Cisplatin (7 mg/kg body wt, intraperitoneal as a single dose); (3) Cisplatin and CDF (50 mg/rat/day; for 12 days); (4) Cisplatin and curcumin (50 mg/rat/day), for 12 days). Cisplatin treated rats exhibited kidney injury manifested by increased serum N-urea and creatinine (P?<?0.001). Kidney from cisplatin treated rats also exhibited significant increase in malondialdehyde (MDA) and 8-isoprostane levels (P?<?0.001). Treatment with CDF and curcumin prevented the rise in serum N-urea, creatinine, MDA and 8-isoprostane as compared to experimental control group in kidney (P?<?0.05). Compared to curcumin, CDF had greater potential in suppressing cisplatin-induced pro-inflammatory factors NF-κB and COX-2 as well as downstream markers Nrf2 and HO-1 (P?<?0.05) in kidney. The analysis on anion transport markers (OAT1 and OAT3) showed a similar trend (CDF?>?curcumin). CDF could reduce the expression of multi-drug resistance markers OCT1, OCT2, MRP2 and MRP4 to a much greater extent than curcumin (P?<?0.05). We also demonstrate that CDF influenced the expression of p-mTOR, p-p70S6K1, p-4E-BP1 and p-Akt. These data suggest that CDF can potentially be used to reduce the chemotherapy induced nephrotoxicity thereby enhancing the therapeutic window of cisplatin. The results also proved that compared to curcumin, CDF has superior protective effect in nephrotoxicity.     

A longitudinal study of radiation-induced changes in tumor vasculature by contrast-enhanced magnetic resonance imaging

Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (V(b)) and permeability (K(2)). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy (137)Cs gamma rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of V(b) and K(2) from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K(2) on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K(2) decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K(2) measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K(2) measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.     

Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice

Molecular Biology Reports - Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently...     

Surfactant protein A and D in the reproductive tract of stallion

The presence of surface-active material in the lung alveolus has been known for several decades as being essential for normal lung function. The host defense and controlling inflammatory processes of the lung are the major functions of SP-A and SP-D. SP-A and SP-D were originally demonstrated in alveolar type II cells, but recent studies have shown extrapulmonary expression of SP-A and SP-D indicating systemic roles of these proteins. Present study describes the presence of SP-A and SP-D in the stallion genital tract, prepuce, prostate, testis, and seminal vesicle using Western blotting and immunohistochemistry. This paper presents the first evidence for the existence of SP-A and SP-D glycoproteins in the stallion genital tract. We examined genital system organs and tissues from stallion and were able to show that surfactant protein A and D reactive with surfactant-specific antibodies were present in the stallion genital tract tissues and organs. On the basis of results, it can be postulated that surfactant proteins in the stallion reproductive tract contribute to the immune surveillance and to active barrier defense mechanism.     

Retinal Neurodegeneration in Wilson’s Disease Revealed by Spectral Domain Optical Coherence Tomography

Background/Objective

In addition to cirrhosis of the liver, Wilson’s disease leads to copper accumulation and widespread degeneration of the nervous system. Delayed visual evoked potentials (VEPs) suggest changes to the visual system and potential structural changes of the retina.

Methods

We used the latest generation of spectral domain optical coherence tomography to assess the retinal morphology of 42 patients with Wilson’s disease and 76 age- and sex-matched controls. We measured peripapillary retinal nerve fiber layer (RNFL) thickness and total macular thickness and manually segmented all retinal layers in foveal scans of 42 patients with Wilson’s disease and 76 age- and sex-matched controls. The results were compared with VEPs and clinical parameters.

Results

The mean thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer was reduced in Wilson’s disease. VEPs were altered with delayed N75 and P100 latencies, but the N140 latency and amplitude was unchanged. An analysis of the laboratory parameters indicated that the serum concentrations of copper and caeruloplasmin positively correlated with the thickness of the outer plexiform layer and with N75 and P100 VEP latencies.

Conclusion

Neuronal degeneration in Wilson’s disease involves the retina and changes can be quantified by optical coherence tomography. While the VEPs and the thickness of the outer plexiform layer appear to reflect the current copper metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer, inner nuclear layer and the total paramacular thickness may be the best indicators of chronic neuronal degeneration.     

Genetic relationships between selected Turkish mulberry genotypes (Morus spp) based on RAPD markers

Mulberry (Morus spp, Moraceae) is an important horticultural crop in Turkey, which is one of the main world producers of mulberry fruit. We evaluated the genetic relationships among 26 mulberry genotypes selected for agronomic characteristics, using RAPD markers. A total of 367 DNA markers were generated with 34 random primers. The highest genetic similarity (0.80) was observed between Oltu58 (M. nigra) and Olur90 (M. nigra) genotypes. The genotypes Oltu3 (M. alba) and Oltu18 (M. rubra) were the most distant (0.36). We found that the RAPD technique is a useful tool to discriminate mulberry genotypes at both the intra- and interspecific level. This type of information will aid in accurate identification of useful genotypes for breeding programs.