Alterations In Proinflammatory Cytokines Research Articles

Necroptosis could serve as an indicator of therapeutic resistance in viral induced well-differentiated oral squamous cell carcinoma?

Goal of the perspectiveExploring necroptosis as an indicator of therapeutic resistance in viral-induced well-differentiated oral squamous cell carcinoma (OSCC) is to elucidate its potential role in predicting treatment outcomes and guiding therapeutic decisions. By understanding the relationship between necroptosis levels and therapeutic resistance, oncologists can aim to identify novel biomarkers and therapeutic targets that could improve patient management and outcomes in viral-induced OSCC. DiscussionViral-induced oral squamous cell carcinoma (OSCC) presents with disrupted cellular functions, dysregulation of apoptotic pathways, evasion of programmed cell death and resistance to conventional anticancer treatments. Concurrently, alterations in pro-inflammatory cytokines and chemokines drive tumorigenesis in viral-induced squamous cell carcinoma, impairing anti-viral immune responses. ConclusionMonitoring necroptosis levels in viral-induced OSCC offers insights into therapy resistance, as high levels may indicate reduced responsiveness to standard treatments. Understanding the role of necroptosis in therapy resistance could pave the way for the development of targeted therapies that exploit necroptosis pathways to overcome resistance and improve treatment outcomes in viral-induced OSCC.

Lactobacillus plantarum Enhanced the Cardioprotective Efficacy of Arctiin in Isoproterenol Cardiac Injury in BALB/c Mice

Background Isoproterenol is a drug used for the treatment of bradycardia that has many side effects due to its non-selective β-adrenoceptor agonist properties. Aim In this study, we evaluated an in vivo experimental model for isoproterenol (ISO) cardiac injury using BALB/c mice and protective treatment with a combined optimized dose of Arctiin (AR) and Lactobacillus plantarum (LP) (ARLP; 30 mg/kg b.w. AR and viable 106 CFU/mL LP p.o.) together. Introduction Isoproterenol causes cardiac injury in many instances. Arctiin is a naturally occurring lignin glycoside present in many herbal medicinal plants that has many beneficial effects for humans. Lactobacillus plantarum is yet another beneficial probiotic that benefits largely to humans. Materials and Methods Male BALB/c mice in appropriate groups (6 animals each) were treated with ARLP for 7 days with ISO administration (100 mg/kg i.p.) on days 5 and 6. On the 8th day, animals were sacrificed. Serum and heart samples were collected for further processing. CK-MB, cardiac troponin, AST, ALT, LDH, GST, GPx, CAT, SOD, GSH, GSSG, MDA, nuclear factor kappa B (NFκB), TNF-α, and IL-6 by ELISA and gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) were estimated in samples. Results Mice administered with ISO showed a prominent rise in the serum marker enzyme activities and tissue oxidative stress markers (MDA and GSSG). Furthermore, marked reductions in body weight and enzymatic and non-enzymatic antioxidant levels were noticed in ISO toxicity. Alterations in proinflammatory cytokines (TNF-α and IL-6) and Nrf2 levels by RT-PCR were analyzed. Histopathology of the heart also indicated cardiac injury in ISO-intoxicated mice. ARLP pretreatment prevented all these cardiac injuries and exerted significant ( p ≤ 0.05) prophylactic protection toward cardiac tissue. Further, we analyzed the possible interactions between AR and LP in vitro, to understand the influence of ARonLP, which showed no significant suppressive/antibacterial activity on LP. Conclusion In conclusion, ARLP exerts a strong cardioprotective and anti-inflammatory activity in cardiovascular injury.

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression.

Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16-18) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks). DEX-dam showed anxiety-like behaviors in open-field test (OFT) and light-dark test (LD). In addition, DEX-dam exhibited depressive-like behaviors with the increased immobility time in forced swimming test (TST). Molecular analysis confirmed that microglia, rather than neurons, astrocytes, and oligodendrocytes, are involved in anxiety-/depressive-like behaviors. Notably, P2ry12, homeostatic gene, and purinoceptor, along with hyper-ramified form, were reduced in the hippocampus of DEX-dam. In addition, we found that IL-10 mRNA was reduced in lymph nodes without alteration of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Interestingly, anxiety-/depressive-like behaviors of DEX-dam were restored with the normalization of P2ry12 and IL-10 after 10 weeks postpartum without antidepressants. Our results propose that stress hormone elevation during pregnancy might be associated with PPD via microglial P2RY12 and peripheral IL-10.

<i>Cassia tora</i> Mitigates Aluminium Chloride Induced Alterations in Pro-inflammatory Cytokines, Neurotransmitters, and Beta-amyloid and Tau Protein Markers in Wistar Rats

Background and Aim: Exposure to Aluminium (Al) has been reported to cause neurotoxicity in laboratory animals. Amyloid-β (Aβ) plaque formation, tau protein hyperphosphorylation, and neuroinflammation have been indicated as the possible mechanism of Al-induced neurodegeneration. The present study aimed to understand the mechanism of aluminium chloride (AlCl3)-induced neurotoxicity in Wistar rats and to assess the neuroprotective effect of methanolic extract of Cassia tora leaves (MECT). Material and Methods: Seventy-two male Wistar rats were randomly divided into nine groups. AlCl3 (100 mg/kg bw) and MECT (300 mg/kg bw) were given orally by gavage and memantine (MEM) was administered intraperitoneally (20 mg/kg bw) to rats, daily for 60 days. The spatial learning memory and recognition memory were evaluated using the Morris Water Maze (MWM) test. The levels of oxidative stress, neurotransmitter markers, pro-inflammatory markers, Aβ proteins plaques formation and tau protein hyperphosphorylation were evaluated. Histopathology of brain tissue was performed to assess the extent of tissue damage on AlCl3 exposure. Results: MECT significantly improved cognitive behaviours in AlCl3-exposed rats during the MWM test. Treatment with MECT resulted in a significant recovery of antioxidant enzyme function, the activity of neurotransmitter markers and pro-inflammatory cytokine levels. MECT prevented the aggregation of Aβ proteins and tau protein phosphorylation. Also, it inhibited the loss of neuronal integrity in the cortex and hippocampus regions of the brain in AlCl3-exposed rats. Conclusion: The findings demonstrate that a methanolic extract of Cassia tora leaves ameliorated AlCl3-induced neurodegeneration in Wistar rats.

Risperidone Administration Attenuates Renal Ischemia and Reperfusion Injury following Cardiac Arrest by Antiinflammatory Effects in Rats.

Multi-organ dysfunction following cardiac arrest is associated with poor outcome as well as high mortality. The kidney, one of major organs in the body, is susceptible to ischemia and reperfusion; however, there are few studies on renal ischemia and reperfusion injury (IRI) following the return of spontaneous circulation (ROSC) after cardiac arrest. Risperidone, an atypical antipsychotic drug, has been discovered to have some beneficial effects beyond its original effectiveness. Therefore, the aim of the present study was to investigate possible therapeutic effects of risperidone on renal IRI following cardiac arrest. Rats were subjected to cardiac arrest induced by asphyxia for five minutes followed by ROSC. When serum biochemical analyses were examined, the levels of serum blood urea nitrogen, creatinine, and lactate dehydrogenase were dramatically increased after cardiac arrest, but they were significantly reduced by risperidone administration. Histopathology was examined using hematoxylin and eosin staining. Histopathological injury induced by cardiac arrest was apparently attenuated by risperidone administration. Furthermore, alterations in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and anti-inflammatory cytokines (interleukin-4 and interleukin-13) were examined by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokine immunoreactivities were gradually and markedly increased and decreased, respectively, in the kidneys following cardiac arrest; however, risperidone administration after cardiac arrest significantly attenuated the increased pro-inflammatory cytokine immunoreactivities and the decreased anti-inflammatory cytokine immunoreactivities. Collectively, our current results revealed that, in rats, risperidone administration after cardiac arrest protected kidneys from IRI induced by cardiac arrest and ROSC through anti-inflammatory effects.

The Alteration of Pro-inflammatory Cytokines and Oxidative Stress Markers at Six-Month Post-living Kidney Donation.

Donors have a higher risk of developing chronic kidney disease than the general population. Some mechanisms mediated by pro-inflammatory cytokines and oxidative stress may be involved as risk factors. The objective of the study was to evaluate the behavior of pro-inflammatory cytokines and oxidative stress markers in living renal donors with a 6-month follow-up. A single prospective cohort was performed in 88 renal donors. At the end of the follow-up, the levels of lipoperoxides, 6.52 ± 1.12 mM, and 8-isoprostanes, 63.75 ± 13.28 pg/mL, were lower than before donation, 10.20 ± 3.95 mM (p < 0.001) and 67.54 ± 9.64 pg/mL (p = 0.026), respectively. Initial levels of nitric oxide (NO), 356.09 ± 59.38 μM increased at the end of the follow-up, 467.08 ± 38.74 μM (p < 0.001). It was observed in the final determination of donors decreased activity of antioxidant enzymes superoxide dismutase (SOD), 0.74 ± 0.57 U/L and glutathione peroxidase (GPx), 556.41 ± 80.37 nmol, in comparison with the levels obtained in the initial determination, 1.05 ± 0.57 U/L (p < 0.001) and 827.93 ± 162.78 nmol (p < 0.001), respectively. The pro-inflammatory cytokines, Tumor necrosis factor alpha and interleukin-6 showed no differences at 6 months after donation. The enzyme oxoguanine glycosylase (hOGG1) responsible for repairing oxidative damage to DNA, showed a decrease in its concentration at the end of the study in donor men, 0.40 ± 0.21 ng/mL compared to the initial levels, 0.55 ± 0.32 ng/mL (p = 0.025). The marker, 8-hydroxy-2-deoxyguanosine (8-OHdG) exhibited an increase in donor men at the final determination 2.28 ± 1.99 ng/mL, compared to the concentration before donation, 1.72 ± 1.96 ng/mL (p < 0.001). We found significant changes in the markers of the oxidative state with increased NO and 8-OHdG, as well as a significant decrease in the antioxidant defenses SOD, GPx, and in the DNA repair enzyme in living renal donors after 6 months of follow-up.

Effects of Melatonin and Flavonoid-Rich Fractions of Chromolaena odorata on the Alteration of Proinflammatory Cytokines and Nitric Oxide Induced by Aflatoxin B1 in the Gastric Mucosa of Wistar Rats.

In this study, we investigated serum interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) after ingestion of aflatoxin B1 (AFB1) in rats. We also studied the effects of nitric oxide (NO) on the stomach after consumption of AFB1. Therefore, we hypothesized that a standard anti-inflammatory agent-melatonin (MEL), and the flavonoid-rich fractions from Chromolaena odorata (FRFC) could counteract the deleterious effects of IL-1β, TNF-α, and NO after consumption of AFB1. Thirty-five Wistar rats (211.86 ± 27.23 g) were randomly selected into 5 groups, with 7 rats in each group. Group A (control); all rats in groups B, C, D, and E received 2.5 mg/kg AFB1 each orally on day 5, whereas those of groups C, D, and E received oral administration of 10 mg/kg MEL, 50 mg/kg FRFC1, and 100 mg/kg FRFC2, respectively, for 7 days. All of them were killed on the 8th day, 24 h after last treatment. Serum samples were analyzed for IL-1β and TNF-α, whereas stomach tissue was evaluated for NO level. Significant (P < 0.5) increase in serum IL-1β and TNF-α in rats given AFB1 only was recorded when compared with those in the control group. Conversely, we observed significant reduction in serum IL-1β and TNF-α in all the groups that received MEL, FRFC1, and FRFC2 after pretreatment with AFB1 when compared with those that were given AFB1 only. In addition, there was a significant increase in NO in rats given AFB1 only when compared with control, whereas reduction in NO was significant in the groups C, D, and E that were given MEL, FRFC1, and FRFC2, respectively, when compared with AFB1 group. MEL and FRFC may be responsible for the prevention of increased gastric mucosal NO and inflammatory effects of proinflammatory cytokines induced by AFB1.

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Anti-inflammatory and renal protective effect of gingerol in high-fat diet/streptozotocin-induced diabetic rats via inflammatory mechanism.

P38 mitogen-activated protein kinase (p38 MAPK), a tissue inflammatory factor can be activated under oxidative stress and in conditions associated with hyperglycemia. Gingerol containing various natural herbs has been extensively studied for its pharmacological actions both in reducing the inflammation and as immunity booster. The aim of the current investigation was to examine the renal protective effect of gingerol in high-fat diet/streptozotocin-induced type II diabetes mellitus in a rat model.NRK 52E cells were divided into normal and high glucose group treated with gingerol. The methylthiazotetrazolium assay was used to establish the cell proliferation progress. Streptozotocin-inducted diabetes in rats was treated with gingerol for 16weeks. The blood glucose, serum creatinine, body weight, food intake, biochemical, antioxidant and haematological parameters were assayed to establish the correlation. Pro-inflammatory cytokines including Il-1β, IL-6, TNF-α; inflammatory mediator COX-2, PGE2, NF-kB, p38MAPK, and TGF-β, were also determined to assess the molecular mechanism. Gingerol exhibited the protective effect on the high glucose level induced NRK 52E cells and did not show any effect on the normal cells. Gingerol significantly (P < 0.001) down-regulated the blood glucose level, creatinine and BUN level in a dose-dependent manner with further significantly (P < 0.001) alteration in pro-inflammatory cytokines, nuclear factor kappa B (N-κB) activation, renal p38MAPK, and TGF-β. From these studies it is possible to predict that gingerol plays a significant role in improving the condition of renal tissue by alteration in p38MAPK and NF-κB activity, and control inflammatory reaction and oxidative stress. Our investigation supports the clinical use of gingerol in future as an effective renal protective agent.

Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3)

Matrix metalloprotease 13 (MMP13) deficiency in pulmonary fibrosis has described contradictory phenotypes on inflammatory and fibrotic responses after lung injury, and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic, and resolution stages were evaluated in Mmp13-null and wild-type (WT) mice. Bronchoalveolar lavage fluid was taken for cytokine array analysis and activity of gelatinases. Our results showed that MMP13 is upregulated mainly during two stages after lung injury, inflammation and resolution of fibrosis, and it is mainly expressed by alveolar and interstitial macrophages. Mmp13-null mice exhibited more extensive inflammation at 7 days after bleomycin treatment, and it was characterized by increased macrophage infiltration and significant alterations in proinflammatory cytokines. We also documented that Mmp13-deficient mice experienced more severe and prolonged lung fibrosis compared with WT mice. Delayed resolution in Mmp13-deficient lungs was characterized by a decreased overall collagenolytic activity and persistent fibrotic foci associated with emphysema-like areas. Together, our findings indicate that MMP13 plays an antifibrotic role and its activity is crucial in lung repair and restoration of tissue integrity during fibrosis resolution.

Alterations of neuroimmune cell density and pro-inflammatory cytokines in response to thimerosal in prefrontal lobe of male rats

Evidence suggests that the effect of heavy metals on neuroimmune cells lead to neurogenic inflammatory responses. In this study, immune cells [mast cells (MCs) and microglia] and pro-neuroinflammation cytokines (interleukin-1b and tumor necrosis factor-α) were assessed in the prefrontal lobe of rat brains exposed to thimerosal in different timeframes. A total of 108 neonatal Wistar rats were divided into three groups having three subgroups. The experimental groups received a single dose of thimerosal (300 μg/kg) postnatally at 7, 9, 11, and 15 days. The vehicle groups received similar injections of phosphate-buffered saline in a similar manner. The control groups received nothing. Samples of the prefrontal cortex were collected and prepared for stereological, immunohistochemical, and molecular studies at timeframes of 12 or 48 h (acute phase) and 8 days (subchronic phase) after the last injection. The average density of the microglia and MCs increased significantly in the experimental groups. This increase was more evident in the 48 h group. At 8 days after the last injection, there was a significant decrease in the density of the MCs compared to the 12 and 48 h groups. Alterations in pro-inflammatory cytokines were significant for all timeframes. This increase was more evident in the 48 h group after the last injection. There was a significant decrease in both neuroinflammatory cytokines at 8 days after the last injection. It was found that ethylmercury caused abnormal neurogenic inflammatory reactions and alterations in the neuroimmune cells that remained for a longer period in the brain than in the blood.

The Dopamine Receptor D3 Regulates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.

BackgroundThe altered expression and function of dopamine receptor D3 (D3R) in patients and animal models have been correlated with depression disease severity. However, the morphological alterations and biological effects of D3R in the brain after inflammation-induced depressive-like behavior remain elusive.MethodsIn the present study, we ascertained the changes of D3R expression in the brain regions after depressive-like behavior induced by peripheral administration of lipopolysaccharide (LPS). Protein levels of proinflammatory cytokines, brain-derived neurotrophic factor (BDNF), and extracellular signal-regulated kinase (ERK1/2)-cAMP-response element-binding protein (CREB) signaling pathway after activation or inhibition of D3R in the brain of depressive mice were also investigated.ResultsLPS caused a significant reduction of D3R in the ventral tegmental area (VTA), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), which are areas related to the mesolimbic dopaminergic system. Pretreatment with pramipexole (PPX), a preferential D3R agonist, showed antidepressant effects on LPS-induced depression-like behavior through preventing changes in LPS-induced proinflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6), BDNF, and ERK1/2-CREB signaling pathway in the VTA and NAc. In opposition, treatment with a D3R selective antagonist NGB 2904 alone made mice susceptible to depression-like effects and caused changes in accordance with the LPS-induced alterations in proinflammatory cytokines, BDNF, and the ERK1/2-CREB signaling pathway in the mPFC and NAc.ConclusionsThese findings provide a relevant mechanism for D3R in LPS-induced depressive-like behavior via its mediation of proinflammatory cytokines and potential cross-effects between BDNF and the ERK1/2-CREB signaling pathway.

Korean red ginseng attenuates doxorubicin-induced testicular dysfunction in rats by modulating inflammatory, oxidative, and autophagy responses

The effect of Korean red ginseng (KRG; Panax ginseng Meyer) against doxorubicin (DOX)-induced testicular inflammation was investigated. Male Sprague-Dawley rats were treated with DOX (1 mg mL−1 kg−1 week−1; intra-peritoneally) for 8 weeks, and KRG water extract (EX1; 100 and EX2; 200 mg/kg/day; orally) was administered for 9 weeks starting one week before DOX exposure. The expression levels related to spermatogenesis, inflammatory and autophagy markers were evaluated using western blotting and reverse transcriptase polymerase chain reaction. DOX-induced a significant (p < .05) alteration in the expression of antioxidation spermatogenesis and sex hormone receptors genes when compared with control groups, which were attenuated with KRG-WE treatment significantly (p < .05 ∼ p < .01). KRG-WE also ameliorated the DOX-induced alteration in pro-inflammatory cytokines via the mitogen-activated protein kinases/nuclear factor kappa-B pathway and autophagy in the testes of rats. In conclusion, KRG might be used as a functional food for prevention of chemotherapy-induced testicular inflammation.

Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1β (IL-1β) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.

Role of interleukin-10 (IL-10) in regulation of GABAergic transmission and acute response to ethanol

Mounting evidence indicates that ethanol (EtOH) exposure activates neuroimmune signaling. Alterations in pro-inflammatory cytokines after acute and chronic EtOH exposure have been heavily investigated. In contrast, little is known about the regulation of neurotransmission and/or modulation by anti-inflammatory cytokines in the brain after an acute EtOH exposure. Recent evidence suggests that interleukin-10 (IL-10), an anti-inflammatory cytokine, is upregulated during withdrawal from chronic EtOH exposure. In the present study, we show that IL-10 is increased early (1 h) after a single intoxicating dose of EtOH (5 g/kg, intragastric) in Sprague Dawley rats. We also show that IL-10 rapidly regulates GABAergic transmission in dentate gyrus neurons. In brain slice recordings, IL-10 application dose-dependently decreases miniature inhibitory postsynaptic current (mIPSC) area and frequency, and decreases the magnitude of the picrotoxin sensitive tonic current (Itonic), indicating both pre- and postsynaptic mechanisms. A PI3K inhibitor LY294002 (but not the negative control LY303511) ablated the inhibitory effects of IL-10 on mIPSC area and Itonic, but not on mIPSC frequency, indicating the involvement of PI3K in postsynaptic effects of IL-10 on GABAergic transmission. Lastly, we also identify a novel neurobehavioral regulation of EtOH sensitivity by IL-10, whereby IL-10 attenuates acute EtOH-induced hypnosis. These results suggest that EtOH causes an early release of IL-10 in the brain, which may contribute to neuronal hyperexcitability as well as disturbed sleep seen after binge exposure to EtOH. These results also identify IL-10 signaling as a potential therapeutic target in alcohol-use disorders and other CNS disorders where GABAergic transmission is altered.

Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis

Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

PENGARUH KONSUMSI MINUMAN BEROKSIGEN TERHADAP INFLAMASI DAN KAPASITAS ANTIOKSIDAN PENDERITA PENYAKIT-PARU-OBSTRUKTIF-KRONIK (PPOK)

PENGARUH KONSUMSI MINUMAN BEROKSIGEN TERHADAP INFLAMASI DAN KAPASITAS ANTIOKSIDAN PENDERITA PENYAKIT-PARU-OBSTRUKTIF-KRONIK (PPOK) [ Influence of Oxygenated Water Consumption in Chronic-Obstructive-Pulmonary-Disease (COPD) Patients ] Fransiska Rungkat Zakaria 1) , Intan Nurul Azni 2) * , Elvira Syamsir 2 ) , Amalia KM. 3) dan Cholid Yamani 3) 1) Departemen Ilmu dan Teknologi Pangan, Fakultas Teknologi Pertanian, Institut Pertanian Bogor, Bogor 2) Program Studi Ilmu Pangan, Fakultas Teknologi Pertanian, Institut Pertanian Bogor, Bogor 3) Klinik dr. Katili, Jl. Raya Dramaga, Bogor Diterima 01 Agustus 2013 / Disetujui 05 Februari 2014 ABSTRACT Chronic Obstructive Pulmonary Disease (COPD) is one of the leading cause of death in the world that represents an important public health problem. Oxygenated water is water added with high concentration of oxygen such that the oxygen concentration is higher than normal water. The objective of this study was to assess the influence of oxygenated water consumption on the alteration of proinflammatory cytokines (TNF-α, IL1-β, and IL6) and antioxidant capacity of COPD patients. Sixteen COPD patients were allowed to drink 385 mL oxygenated water two times a day for 21 days. The alteration of proinflammatory cytokines and antioxidant capacity are measured by comparing plasma concentration before and after intervention. The results suggest that oxygenated water consumption significantly reduce proinflammatory cytokines plasma (TNF-α, IL1-β, and IL6) at 5% significance level with 81.25 % of respondents having lower TNF-α, 75% of respondents with lower IL-1β, and 62 . 25 % of respondents having lower the IL-6 in plasma concentration after 21 days intervention. There were 43 . 75 % of respondents with decrease d antioxidant capacity concentration. However, it was not significant at the 5 % level significance . Decrease in antioxidant capacity was probably a resulted from poordiet and drugs consumption during the intervention period .

Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression.

Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α) as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II), traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40), and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively), and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years). The results show that TNF-α is significantly related to DES (Spearman R=−0.42, P<0.01), SDQ-20 (Spearman R=−0.38, P<0.01), and TSC-40 (Spearman R=−0.41, P<0.01), but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients.

ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency.

Angiotensin II causes imbalance between pro‐ and anti‐inflammatory cytokines by modulating GSK‐3β in neuronal culture

Emerging evidence indicates that the balance between pro-inflammatory cytokines (PICs) and anti-inflammatory cytokines (AICs) within the brain is an important determinant in the outcome of hypertension. However, the mechanism by which this dysregulation occurs is not known. We aimed to investigate whether AngII induces imbalance between PIC and AIC by modulating downstream transcription factors, NFκB and cyclic AMP response element-binding protein (CREB), and whether AngII-induced effects are mediated by glycogen synthase kinase-3β (GSK-3β). CATH.a neurons were exposed to AngII (10 nM-1 μM) over a preset time course. In another set of experiments, GSK-3β was knock down by using lentivirus containing short hairpin RNA targeting GSK-3β (L-sh-GSK3β) before AngII exposure. Cell extracts were subjected to RT-PCR, immunoblot and immunoprecipitation. AngII caused time-dependent increase in PICs (TNF-α and IL-1β) and reduction in AIC (IL-10). AngII exposure caused reduced phosphorylated CREB(Ser-133) and increased p-NFκB(Ser-276) levels, leading to reduced CREB-CBP and increased NFκB-CBP binding. These results were accompanied by increased activation of GSK-3β, as indicated by increased p-GSK3(Tyr-216) to p-GSK3(Ser-9) ratio. In a subsequent study, pretreatment with L-sh-GSK3β attenuated AngII-induced alterations in PICs and IL-10 by augmenting CREB-CBP and attenuating NFκB-CBP binding. Collectively, these findings are the first to provide direct evidence that AngII-induced dysregulation in cytokines is mediated by GSK-3β-mediated alterations in downstream transcription factors in neuronal cells. Our data also reveal that AngII-induced effects could be alleviated by GSK-3β inhibition, suggesting GSK-3β as an important therapeutic target for hypertension that is characterized by increased PICs and NFκB activation.