Progranulin: A proangiogenic factor in visceral adipose tissue in tumoral and non-tumoral visceral pathology.

The connection between central obesity and the development and metastasis of various visceral tumors is largely accepted and one of the main causes seems to be the local synthesis of proangiogenic molecules. Progranulin (PRG), recently identified as an adipokine, is a novel pleiotropic growth factor acting on the proliferation and development of fast-growing epithelial cells, cancer cells, and also a proangiogenic factor whose expression is induced in activated endothelial cells. One of the molecules that seems to trigger the angiogenic activity of PRG is vascular endothelial growth factor (VEGF). Two groups of human subjects were considered and adipose tissue was processed for an immunohistochemical and morphometric study after surgery for abdominal tumoral or non-tumoral pathology. The presence of PRG in adipose pads of the omentum was analyzed and its association with VEGF, CD34 and collagen IV in tumoral and non-tumoral visceral pathology was examined. The results showed that PRG but not VEGF expression was upregulated in adipose tissue in tumoral visceral pathology. In conclusion, the involvement of the proangiogenic activity of PRG and VEGF in adipose tissue under tumor conditions may be dependent on the visceral tumor type.

Interrelation of inflammation and oxidative stress in liver cirrhosis.

Recently, the trend of research has been focused on the role of hematological indicators in assessing the activities of various diseases. The aim of the present study was to determine the usefulness of such hematological indicators for assessment of the relationship between inflammation and oxidative stress in order to provide new predictive tools for a non-invasive investigation of disease outcome for liver cirrhosis patients. A total of 35 subjects with compensated or decompensated liver cirrhosis and 10 age-matched healthy volunteers were included in this study. The patients were divided into two groups: Group 1, patients with toxic metabolic cirrhosis due to ethanol consumption; group 2, patients with liver cirrhosis following hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Using hematological data obtained after the complete counting of peripheral blood cells, the monocyte/lymphocyte (MLR), neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios as well as systemic immune inflammation biomarkers were determined. The erythrocyte sedimentation ratio (ESR), C-reactive protein (CRP), fibrinogen and biochemical parameters related to liver function were also registered. Thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCARB), and total antioxidant capacity (TAC) were also investigated in the peripheral blood samples of healthy subjects and liver cirrhosis patients. The results revealed that NLR, MLR and PLR were significantly increased in group 2. PLR was significantly increased in group 1 compared with that noted in the control group. TBARS and PCARB were increased in patients from group 1 compared to patients from group 2 and the control group. However, no difference in TAC was found between the liver cirrhosis groups and the control. We showed that the pro-inflammatory status of liver cirrhosis patients can be easily appreciated by NLR, MLR but not PLR. However, the increase in these ratios was not significantly associated with a decrease in the antioxidant capacity and an augmentation of oxidative stress markers for the patients diagnosed with cirrhosis included in the two groups of study.

NAD+ metabolism and retinal degeneration (Review).

The recent years has revealed an intense interest in the study of nicotinamide adenine dinucleotide (NAD+), particularly in regards to its intermediates, such as nicotinamide and nicotinic acid known as niacin, and also nicotinamide riboside. Besides its participation as a coenzyme in the redox transformations of nutrients during catabolism, NAD+ is also involved in DNA repair and epigenetic modification of gene expression and also plays an essential role in calcium homeostasis. Clinical and experimental data emphasize the age-dependent decline in NAD+ levels and its relation with the onset and progression of various age-related diseases. Maintaining optimal levels of NAD+ has aroused a therapeutic interest in such pathological conditions; NAD+ being currently regarded as an important target to extend health and lifespan. Based on a systematic exploration of the experimental data and literature surrounding the topic, this paper reviews some of the recent research studies related to the roles of the pyridine nucleotide family focusing on biosynthesis, NAD+ deficiency-associated diseases, pathobiochemistry related to retinal degeneration and potential therapeutic effects on human vision as well.

Variations of Serum Oxidative Stress Biomarkers under First-Line Antituberculosis Treatment: A Pilot Study.

Tuberculosis (TB) is one of the highest infectious burdens worldwide, and pathogenesis is yet incompletely elucidated. Bacilli dissemination is due to poor antioxidant defense mechanisms and intensified oxidative stress. There are few recent studies that analyzed and compared free radicals or antioxidant status before and after anti-TB treatment. Hence, the present study underlines the need to identify oxidative stress as it could be a useful tool in TB monitorisation. Thirty newly diagnosed patients with pulmonary TB were included after signing an informed consent. Blood was collected before receiving first-line anti-tubercular therapy (T0) and after 60 days (T2). Spectrophotometric methods were used to quantify oxidative parameters (TBARS-thiobarbituric acid reactive species); enzymatic antioxidants such as SOD (superoxide dismutase), CAT (catalase), GPx (glutathione peroxidase), and TAC (total antioxidant capacity); and non-enzymatic antioxidants such as GSH (reduced glutathione). A moderate positive correlation was found between GSH and TAC (r = 0.63, p-value = 0.046) and GSH and SOD (r = 0.64, p-value = 0.041) at T2. Increased values of GSH, CAT, and SOD were noted at T2 in comparison with T0, while GPx, TAC, and TBARS decreased at T2. A better monitorisation in TB could be based on oxidative stress and antioxidant status. Nevertheless, restoring redox host balance could reduce TB progression.

Hepatoprotective effect of Syringae vulgaris flos ethanolic extracts in streptozotocin-induced diabetes in rats.

Taking account of increasing world population life expectancy, health services will face with a large number of elderly people with chronic age-related diseases. It has been established that chronic diseases are usually accompanied by oxidative stress induced by the overproduction of reactive oxygen species damaging cellular constituents, under conditions of weakening antioxidant defense systems. The balance between free radicals and antioxidant endogenous systems has a defining role in preventing the damage of macromolecules. In addition to the enzymatic (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase) and non-enzymatic (vitamins A, C, E) endogenous systems, a good source of natural antioxidants are medicinal herbs products or phytochemical compounds. The aim of this study is to evaluate the hepatoprotective effect of Syringae vulgaris flos ethanolic extracts in a rat model of streptozotocin-induced diabetes.

Heterogeneity of collagen secreting cells in gingival fibrosis--an immunohistochemical assessment and a review of the literature.

AIM: In this work, we compared the histological features of the gingival lesions clinically diagnosed as fibrotic overgrowths due to various etiologic factors as well as an immunohistochemical assessment of fibroblasts phenotypic heterogeneity using the specific labeling for vimentin, α-smooth muscle actin (α-SMA) and fibroblast specific protein-1 (FSP1). MATERIALS AND METHODS: Tissue samples were obtained from 12 patients clinically diagnosed with fibrotic gingival overgrowth, divided in four groups. Fragments of gingiva were processed for paraffin embedding. Serial sections were used for routine staining Hematoxylin-Eosin, trichromic Masson and Goldner-Szekely, and for immunohistochemical reactions to label vimentin, α-SMA and FSP1 using for signal amplification several techniques (EnVision, LSAB, ABC). RESULTS: Storage of collagen fibers, increase of fibroblast number and frequent presence of inflammatory infiltrate are histological issues of all fibrotic gingival overgrowth. The incidence of granulation tissue varies but the frequency of its presence point the attention to the involvement in collagen metabolism imbalance. Immunostaining for vimentin showed a difference between its expression in samples from different groups. Except the cases of fibrosis induced by orthodontic devices, cells positive for α-SMA were rare. FSP1-positive fibroblasts were the most frequent in all cases from all the groups selected for this study. CONCLUSIONS: The phenotype of fibroblasts is different in gingival fibrosis in relation to the risk factor, at present the most common being vimentin-positive and FSP1-positive fibroblasts. Myofibroblasts are rare in gingival fibrosis, the most numerous being in local lesions caused by wearing orthodontic devices and in syndromic fibromatosis. Further studies are required to elucidate the manner in which the active fibroblasts are recruited in relation to the etiologic factor of gingival overgrowth.

Inducible nitric oxide synthase expression (iNOS) in chronic viral hepatitis and its correlation with liver fibrosis.

BACKGROUND: Nitric oxide (NO) production by the action of the inducible nitric oxide synthase (iNOS or NOS2) is increased in tissues that are stimulated by cytokine and endotoxins. The role of NO in the pathogenesis of chronic viral hepatitis is not fully understood but it seems that its overproduction is responsible for the pathological changes under inflammatory conditions. AIM: In this paper, we analyzed the correlation between immunohistochemical expression of iNOS and liver fibrosis in chronic viral hepatitis. MATERIALS AND METHODS: Liver biopsies from patients diagnosed with chronic viral hepatitis B and C were embedded in paraffin and further used for histological staining and immunohistochemical reactions to detect the expression of iNOS and TGF-ß1. The degree of liver fibrosis was established using special staining (trichromic Masson and Gömöri's silver impregnation). RESULTS: In samples with low degree of fibrosis, we observed a discrete positivity for iNOS in periportal hepatocytes and the immunohistochemical reaction for TGF-ß1 were limited to the endothelial cells of liver sinusoids and pro-inflammatory cells from the portal tracts. Positive reaction for TGF-ß1 increased with the degree of liver fibrosis, while the expression of iNOS was enhanced in hepatocytes, as well as in bile ducts and endothelial cells. CONCLUSIONS: Infection with hepatitis B and C viruses induces iNOS expression in hepatocytes, suggesting that NO overproduction might have an important role in progression of chronic viral hepatitis to cirrhosis.

Role of transforming growth factor ß-connective tissue growth factor pathway in dihydropyridine calcium channel blockers-induced gingival overgrowth.

BACKGROUND: Gingival overgrowth was reported as a side effect after chronic administration of several drugs, which, despite their different pharmacological effect, seem to have the gingival mucosa as a secondary target. The thickness of the gingival epithelium and fibrosis in the lamina propria are unspecific changes that together determine the enlargement of the gingival mucosa, but the molecular mechanisms responsible for the imbalance of collagen synthesis/breakdown are still uncertain. The aim of our study was to assess the role of TGF-ß1-CTGF pathway in the activation of cells with a fibrilogenetic phenotype responsible for the gingival fibrosis developed after chronic administration of dihydropyridine calcium channel blockers. MATERIALS AND METHODS: Fragments of gingival tissue collected from patients clinically diagnosed with gingival overgrowth after chronic administration of nifedipine and amlodipine were processed for paraffin embedding. Serial sections were used for routine staining Masson and Gömöri's silver impregnation in order to reveal collagen accumulation and for immunohistochemical reactions to label TGF-ß1, CTGF, Ki67 and α-SMA. RESULTS: Routine histological staining for collagen revealed the presence of gingival fibrosis and a change between type I collagen/type III collagen ratio. Regardless of the drug involved, many slides showed extended TGF-ß1 positive areas, mainly in the profound - spinous and basal - layers, but also in some cells from the subjacent connective tissue. CTGF exposed intense positive reaction in the basal and parabasal layers, but also in resident cells from the connective tissue. Ki67 immunolabeling did not reveal an increased fibroblast proliferation in the lamina propria. We noticed the presence of a small number of myofibroblasts in the lamina propria. CONCLUSIONS: These findings suggest that TGF-ß1-CTGF axis is activated in dihydropyridine calcium channel blockers-induced gingival overgrowth and exerts a different control on the activation of fibroblasts with a synthetic phenotype. These results also have implications for better understanding mechanisms of fibrosis and the future use of this pathogenic pathway as a therapeutic target in order to limit gingival fibrosis.