Abstract: Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. 43 children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by the World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children, whose BMI percentile values were between 99 and 95, comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analyses, including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %) and ferritin, were performed. sTWEAK levels were determined by enzyme-linked immunosorbent assay. study data were evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91 ± 34 mcrg/dl and 75 ± 31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs. 299 mcrg/dl, 37.2 ± 19.1% vs. 26.7 ± 14.6%, and 41 ± 25 ng/ml vs 44 ± 26 ng/ml. In N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p > 0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p < 0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is an inducer of apoptosis. OB children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of OB children.
Abstract: Obesity, as excessive fat accumulation in the body, is a global health problem. The prevalence of obesity and its complications increase due to easy access to high-energy food and decreased physical activity. Cardiovascular diseases (CVDs) constitute a significant part of obesity-related morbidity and mortality. Since the effects of obesity on cardiovascular system may start during childhood without clinical findings, elucidating the mechanisms of cardiovascular changes associated with childhood obesity became more important. In this study, we aimed to investigate some biochemical parameters which may be involved in obesity-related pathologic processes of CVDs. One hundred and seventy-seven children were included in the study, and they were divided into four groups based upon WHO criteria and presence of the metabolic syndrome (MetS): children with normal-BMI, obesity, morbid obesity, and MetS. High-sensitive cardiac troponin T (hs-cTnT), cardiac myosin binding protein C (cMyBP-C), trimethylamine N-oxide (TMAO), soluble tumor necrosis factor-like weak inducer (sTWEAK), chromogranin A (CgA), multimerin-2 levels, and other biochemical parameters were measured in serum samples. Anthropometric measurements and clinical findings of the children were recorded. Statistical analyses were performed. Children with normal-BMI had significantly higher CgA levels than children with obesity, morbid obesity, and MetS (p < 0.05). Cardiac MyBP-C levels of children with MetS were significantly higher than of children with normal-BMI and OB children (p < 0.05). There was no significant difference in hs-cTnT, sTWEAK, TMAO and multimerin-2 between the groups (p>0.05). These results suggested that cMyBP-C and CgA molecules may be involved in the pathogenesis of obesity-related CVDs.
Abstract: Background: Physical exercise induces a pattern of hormonal and immunological responses that prevent endothelial dysfunction by maintaining the availability of nitric oxide (NO). Regular and moderate exercise stimulates NO release, that can be considered as protective factor of cardiovascular diseases, while strenuous exercise induces increased levels in a number of pro-inflammatory and anti-inflammatory cytokines. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) triggers endothelial activation which results in an increased vascular permeability. Nuclear gene factor kappa B (NF-κB) activates biological effect of TNF-α. Aim of Study: To determine the effect of physical exercise on the endothelial and skeletal muscle, we measured the level of NF-κB on rats’ serum, macrophages, and myocytes after strenuous physical exercise. Methods: 30 male Rattus norvegicus in the age of eight weeks were randomly divided into five groups (each containing six), and there were treated groups (T) and control group (C). The treated groups obtain strenuous physical exercise by ran on treadmill at 32 m/minutes for 1 hour or until exhaustion. Blood samples, myocytes of gastrocnemius muscle, and intraperitoneal macrophages were collected sequentially. There were investigated immediately, 2 hours, 6 hours, and 24 hours (T1, T2, T3, and T4) after sacrifice. The levels of NF-κB were measured by ELISA methods. Results: From our study, we found that the levels of NF-κB on myocytes in treated group from which its specimen was taken immediately (T1), 2 hours after treadmill (T2), and 6 hours after treadmill (T3) were significantly higher than control group (p0.05). Also on macrophages, NF-κB in treated groups T1, T2, and T3 was significantly higher than control group (p0.05). The level of serum NF-κB was not significantly different between treatment group as well as compared to control group (p>0.05). Serum NF-κB was significantly higher than the level on macrophages and myocytes (p
Abstract: Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E2 (PGE2) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE2 levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE2 levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE2 level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE2 levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.
Abstract: The present study investigated the protective effect of
thymoquinone (TQ), against cadmium-induced kidney injury in rats.
Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine
weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of
cadmium administration and continued for nine weeks. TQ
significantly decreased serum creatinine, renal malondialdehyde and
nitric oxide, and significantly increased renal reduced glutathione in
rats received cadmium. Histopathological examination showed that
TQ markedly minimized renal tissue damage induced by cadmium.
Immunohistochemical analysis revealed that TQ markedly decreased
the cadmium-induced expression of inducible nitric oxide synthase,
tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal
tissue. It was concluded that TQ significantly protected against
cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory,
and antiapoptotic actions.
Abstract: Ficus deltoidea from the Moraceae family is a popular
medicinal herb in Malaysia. It possesses strong antioxidant and antiinflammatory
properties. In the present study, the anti-inflammatory
effects of F. deltoidea extract on UVB-irradiated HaCaT
Keratinocytes were investigated. HaCaT Keratinocytes were UVBirradiated
(12.5 mJ/cm3) and were treated with 0.05, 0.08 or 0.1% of
F. deltoidea extract. Cell viability following UVB irradiation was
significantly higher in the groups treated with the F. deltoidea extract
at doses of 0.05, 0.08 or 0.1% than in control group with UVB
irradiation only. Tumor necrosis factor-α (TNF-α), interleukin-1α
(IL-1α), interleukin-6 (IL-6) and cyclooxygenase (COX-2) play
primary roles in the inflammation process upon UV irradiation and
are known to be stimulated by UVB irradiation. Treatment with the
F. deltoidea extract dramatically inhibited the UV-induced TNF-α,
IL-1α, IL-6, and COX-2 expression. These results suggest that the F.
deltoidea extract inhibits the production of pro-inflammatory
cytokines and may be an effective protective agent for the treatment
of skin diseases.
Abstract: Heme oxygenase-1 (HO-1), an enzyme degrading heme to carbon monoxide, iron, and biliverdin, has been recognized as playing a crucial role in cellular defense against stressful conditions, not only related to heme release. In the present study, the effects of TNF-a on the expression of heme oxygenase-1 (HO-1) in human aortic endothelial cells (HAECs) as well as the related mechanisms were investigated. 10 ng/mL TNF-α treatment significantly increased HO-1 expression after 6h, then a further increase at 12h and declined at 24h. Treatment with 2 ng/mL of TNF-a after 12 h resulted in a significant increase in HO-1 expression, which peaked at 10 ng/mL, then declined at 20 ng/mL. TNF-α induced HO-1 expression and then HO-1 expression reduced vascular cell adhesion molecule-1 (VCAM-1) expression. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen-activated protein kinases (MAPKs) demonstrated TNF-α-induced ERK1/2, JNK, and p38 phosphorylation. The increase in HO-1 expression in response to TNF-α treatment was affected by pretreatment with SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), not with PD98059 (an ERK1/2 inhibitor). The expression of HO-1 was stronger in aortas of TNF-α-treated apo-E deficient mice when compared with control mice. These results suggest that low dose of TNF-α treatment notably induced HO-1 expression was mediated through JNK/p38 phosphorylation and may have a protective potential in cardiovascular diseases and inflammatory response through the regulation of HO-1 expression.
Abstract: In the present research, two nutraceuticals made from
red grape and walnut that showed previously to improve kidney
dysfunction were incorporated separately into functional foods' bread
made from barley and rice bran. The functional foods were evaluated
in rats in which chronic renal failure was induced through feeding
diet rich in adenine and phosphate (APD). The evaluation based on
assessing kidney function, oxidative stress, inflammatory biomarkers
and body weight gain. Results showed induction of chronic kidney
failure reflected in significant increase in plasma urea, creatinine,
malondialdehyde, tumor necrosis factor- α and low density
lipoprotein cholesterol along with significant reduction of plasma
albumin, and total antioxidant and creatinine clearance and body
weight gain on feeding APD compared to control healthy group.
Feeding the functional foods produced amelioration in the different
biochemical parameters and body weight gain indicating
improvement in kidney function.
Abstract: NFκB activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFa) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are no any quantitative or qualitative results of comparison assessment on inhibition effect between different single drugs or drug combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific single drugs and drug combinations on the NFκB pathway in MM, especially the prediction of synergistic drug combinations.
Abstract: We present a label-free biosensor based on
electrochemical impedance spectroscopy for the detection of proinflammatory
cytokine Tumor Necrosis Factor (TNF-α). Secretion of
TNF-α has been correlated to the onset of various diseases including
rheumatoid arthritis, Crohn-s disease etc. Gold electrodes were
patterned on a silicon substrate and self assembled monolayer of
dithiobis-succinimidyl propionate was used to develop the biosensor
which achieved a detection limit of ~57fM. A linear relationship was
also observed between increasing TNF-α concentrations and chargetransfer
resistance within a dynamic range of 1pg/ml – 1ng/ml.