Effects of four weeks lasting aerobic physical activity on cardiovascular biomarkers, oxidative stress and histomorphometric changes of heart and aorta in rats with experimentally induced hyperhomocysteinemia.

The aim of this study was to examine the effects of hyperhomocysteinemia and aerobic physical activity on changes of cardiovascular biomarkers in sera, oxidative stress in cardiac tissue, and histomorphometric parameters of heart and aorta in rats. Experiments were conducted on male Wistar albino rats organized into four groups (n = 10, per group): C (control group): 0.9% NaCl 0.2 mL/day; H (homocysteine group): homocysteine 0.45 µmol/g b.w./day; CPA (control + physical activity group): 0.9% NaCl 0.2 mL/day and a program of physical activity on a treadmill; and HPA (homocysteine + physical activity group) homocysteine 0.45 µmol/g b.w./day and a program of physical activity on a treadmill. Substances were applied subcutaneously twice a day. Lipid peroxidation and relative activity of Mn-superoxide dismutase isoform were significantly higher in active hyperhomocysteinemic rats in comparison to sedentary animals. Atherosclerotic plaques were detected in aorta samples of active hyperhomocysteinemic rats and also, they had increased left ventricle wall and interventricular septum, and transverse diameter of cardiomyocytes compared to sedentary groups. Aerobic physical activity in the condition of hyperhomocysteinemia can lead to increased oxidative stress in cardiac tissue and changes in histomorphometric parameters of the heart and aorta, as well increased lipid parameters and cardiac damage biomarkers in sera of rats.

Intestinal Ultrasonography as a Tool for Monitoring Disease Activity in Patients with Ulcerative Colitis.

Background: Ultrasonography is a noninvasive, inexpensive, and widely available diagnostic tool. In the last two decades, the development of ultrasound techniques and equipment has significantly increased the usage of intestine ultrasound (US) in the assessment of the gastrointestinal tract in patients with inflammatory bowel disease (IBD). Although current guidelines suggest routine utilization of US in patients with Crohn's disease, data regarding US usage in ulcerative colitis are still scarce. We aimed to assess the reliability of intestinal ultrasonography in the assessment of disease activity and extension of patients with ulcerative colitis. Methods: Fifty-five patients with a histologically confirmed diagnosis of ulcerative colitis, treated at University Clinical Center of Serbia in the period from 2019 to 2022 were included in this retrospective observational study. The data were obtained from the patient's medical records including history, laboratory, US, and endoscopy findings. US examined parameters were as following: bowel wall thickness (BWT), presence of fat wrapping, wall layer stratification, mesenteric hypertrophy, presence of enlarged mesenteric lymph nodes, and absence or presence of ascites. Results: Our results suggest that there is a strong correlation of BWT and colonoscopy findings regarding disease extension (r = 0.524, p=0.01, p < 0.05). Furthermore, our results have shown a statistically significant correlation of BWT with the Mayo endoscopic score (r = 0.434, p=0.01, p < 0.05), disease activity score (r = 0.369,p=0.01, p < 0.05), degree of ulcerative colitis burden of luminal inflammation (r = 0.366, p=0.01, p < 0.05), and Geboes index (r = 0.298, p=0.027, p < 0.05). Overall accuracy of US for disease extension and activity was statistically significant (p < 0.05). Conclusions: Our results suggest that US is a moderately accurate method for the assessment of disease activity and localization in patients with UC.

Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis.

The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (-IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with -IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.

Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease.

RESULTS: There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (P < 0.01). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively (P > 0.05). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin (P < 0.01). CONCLUSION: Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.

Substituent Effect on Triplet State Aromaticity of Benzene.

Density functional theory calculations have been performed to explore the substituent effect on benzene's structure and aromaticity upon excitation to the first triplet excited state (T1). Discussion is based on spin density analysis, HOMA (harmonic oscillator model of aromaticity), NICS (nucleus-independent chemical shift), ACID (anisotropy of the induced current density), and monohydrogenation free energies and shows that a large span of aromatic properties, from highly antiaromatic to strongly aromatic, could be achieved by varying the substituent. This opens up a possibility of controlling benzene's physicochemical behavior in its excited state, while molecular motion, predicted for several derivatives, could be of interest for the development of photomechanical materials.

Effects of subchronic methionine stimulation on oxidative status and morphological changes in the rat ileum.

This study was conducted to explore the effects of sulfur containing amino acids on redox status and morphological parameters in the rat ileum tissue. Male Wistar albino rats were randomly divided into the following groups: Group K (saline (1 ml/day, i.p.)), Group M (methionine (0.8 mmol/kg/day, i.p.)), Group C (methionine (0.8 mmol/kg/day) + L-cysteine (7 mg/kg/day), i.p.) and Group N (methionine (0.8 mmol/kg/day) + N-acetyl-L-cysteine (50 mg/kg/day), i.p.). Activities of antioxidant enzymes in the ileum were analyzed to profile oxidative status. Morphometric analysis included measurement of villus height (µm), tunica mucosa thickness (µm), tunica muscularis thickness (µm), the total thickness of the ileal wall (µm) and the number of cells in the lamina propria (per 0.1 mm2 of tissue). Results showed that methionine treatment reduced the activity of antioxidant enzymes (SOD, GPx, CAT) and the GSH content compared to the control group (p > 0.05). The application of methionine reduced the following parameters statistically significant compared to the control group: length of the ileal villi (p < 0.01), tunica mucosa thickness (p < 0.01), and ileal wall thickness (p < 0.01). We concluded that methionine induced the changes in the gut redox status, which implied oxidative stress occurrence. L-cysteine and N-acetyl-L-cysteine both exhibited antioxidant properties.

Triplet-State Structures, Energies, and Antiaromaticity of BN Analogues of Benzene and Their Benzo-Fused Derivatives.

It is well known that benzene is aromatic in the ground state (the Hückel's rule) and antiaromatic in the first triplet (T1) excited state (the Baird's rule). Whereas its BN analogues, the three isomeric dihydro-azaborines, have been shown to have various degrees of aromaticity in their ground state, almost no data are available for their T1 states. Thus, the purpose of this work is to theoretically [B3LYP/6-311+G(d,p)] predict structures, energies, and antiaromaticity of T1 dihydro-azaborines and some benzo-fused derivatives. Conclusions are based on spin density analysis, isogyric and hydrogenation reactions, HOMA, NICS, and ACID calculations. The results suggest that singlet-triplet energy gaps, antiaromaticity, and related excited-state properties of benzene, naphthalene, and anthracene could be tuned and controlled by the BN substitution pattern. While all studied compounds remain (nearly) planar upon excitation, the spin density distribution in T1 1,4-dihydro-azaborine induces a conformational change by which the two co-planar C-H bonds in the ground state become perpendicular to each other in the excited state. This predicted change in geometry could be of interest for the design of new photomechanical materials. Excitation of B-CN/N-NH2 1,4-azaborine would have a few effects: intramolecular charge transfer, aromaticity reversal, rotation, and stereoelectronic Umpolung of the amino group.

Can Variations of 1 H†NMR Chemical Shifts in Benzene Substituted with an Electron-Accepting (NO2 )/Donating (NH2 ) Group be Explained in Terms of Resonance Effects of Substituents?

The classical textbook explanation of variations of 1 H NMR chemical shifts in benzenes bearing an electron-donating (NH2 ) or an electron-withdrawing (NO2 ) group in terms of substituent resonance effects was examined by analyzing molecular orbital contributions to the total shielding. It was found that the π-electronic system showed a more pronounced shielding effect on all ring hydrogen atoms, relative to benzene, irrespective of substituent +R/-R effects. For the latter, this was in contrast to the traditional explanations of downfield shift of nitrobenzene proton resonances, which were found to be determined by the σ-electronic system and oxygen in-plane lone pairs. In aniline, the +R effect of NH2 group can be used to fully explain the upfield position of meta-H signals and partly the upfield position of para-H signals, the latter also being influenced by the σ-system. The position of the lowest frequency signal of ortho-Hs was fully determined by σ-electrons.

Suppression of methionine-induced colon injury of young rats by cysteine and N-acetyl-L-cysteine.

Changes in the methionine metabolism can cause a state called hyperhomocysteinemia, inducing oxidative stress in the gut. The production of free radicals is important in the colon damage caused by methionine. This study aimed at evaluating the effect of the use of L-cysteine and N-acetyl-L-cysteine on the colon morphometry of young rats treated with methionine. A total number of 32 male rats were distributed in a randomized experimental design in 4 groups: control group treated with saline; methionine group; cysteine + methionine group, and N-acetyl-L-cysteine + methionine group. After 21 days of treatment, rats were sacrificed and the colon samples were taken for histological and biochemical analysis. Methionine load increased depth of crypts, the lamina muscularis mucosae thickness, the mucosal height, and the number of cells in lamina propria (p < 0.01). Combination of methionine with L-cysteine (C group) and with N-acetyl-L-cysteine (N group) reversed methionine effects. Methionine treatment increased the GPx activity and MDA concentration, while L-cysteine and N-acetyl-L-cysteine increased the catalase activity compared to methionine group. It was concluded that the use of L-cysteine and N-acetyl-L-cysteine was beneficial to decrease intestinal mucosal height and oxidative damage when methionine was used in combination with them.

Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state.

To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1ß (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1ß (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1ß expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1ß expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.