Tissue Tumor Necrosis Factor Research Articles

Evaluation of Adipose Tissue Hormones and Tumor Necrosis factor in Patients with Endometriosis

Objective: To evaluate levels of physiological parameters (Testosterone, follicle stimulating hormone FSH, luteinizing hormone LH, leptin and tumor necrosis factor TNF-α, Adipsin and Ghrelin), Total antioxidant capacity-TAC, Glutathione S transfers -GST in sera of patients with endometriosis. Method: This study involved (85) women within reproductive age (25-40) years, who were distributed into two groups: patientsʹ group (55) women diagnosed with endometriosis, and (30) healthy control women. The study was carried out at Al-Karkh Maternity Hospital/ Baghdad and extended from 20/4/2024 to 20/5/2024. The pathological cases of patients were diagnosed by clinical examinations and confirmed by specialist physician with ultrasound examination. Blood samples were taken from both groups, serum was separated for each individual by a centrifuge. Results: a significant rise in the (FSH, Leptin, TNF -α, Adipisin) while a significant decrease in levels of (Testosterone , LH, GST, TAC, Ghrelin) concentration were found in the sera of patients compered to healthy women , with a probability of P ≤ 0.05. According to Receiver operating characteristic (ROC) statistical analysis, Area under curve (AUC ) for LH, leptin, TNF -α, adipsin, ghrelin, GST, TAC were closely or equal to (1) for patients . Conclusion: serum levels of LH, Leptin, Adipisin, Gherlin, TNF-α and GST can be dependable as prognostic indicator markers that reflect the degree of oxidative stress accompanying endometriosis.

Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis.

Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses. Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg-1 h-1 ), renal arterial tempol (RAT; 3 mg kg-1 h-1 ), or vehicle. Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min-1 ). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015). In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.

Neuroprotective Effects of Milrinone on Acute Traumatic Brain Injury

Traumatic brain injury is still an important health problem worldwide. Traumatic brain injury not only causes direct mechanical damage to the brain but also induces biochemical changes that lead to secondary nerve cell loss. In this study, we investigated the neuroprotective effect of milrinone after traumatic brain injury (TBI) in a rat model. Forty male Wistar albino rats, were used. Rats were divided into 4 groups: 1) sham, 2) TBI, 3) TBI+Ringers, and 4) TBI+Milrinone. In group 1 (sham), only craniotomy was performed. In group 2 (TBI), TBI was performed after craniotomy. In group 3 (TBI+Ringer), TBI was performed after craniotomy and intraperitoneal Ringers solution was given immediately afterward. Group 4 (TBI+Milrinone), TBI was performed after craniotomy, and milrinone was given 1.0mg/kg milrinone intraperitoneally directly (0.5mg/kg milrinone intraperitoneally again 24hours, 48hours, and 72hours after trauma). Tests were performed for neurological and neurobehavioral functions. Immunohistochemistry and histopathology studies were performed. In group 4 compared with group 2 and group 3 groups, tests for neurological functions and neurobehavioral functions were significantly better. In the milrinone treatment used in group 4, plasma and brain tissue tumor necrosis factor, 8-OH 2-deoxyguanosine , and interleukin 6 levels were significantly decreased, and increased plasma and tissue IL-10 levels were detected. Histopathological spinal cord injury and apoptotic index increased in groups 2 and 3, while significantly decreasing in group4. This study shows for the first time that the anti-inflammatory, antioxidant and antiapoptotic properties of milrinone may be neuroprotective after TBI.

Influence of Maternal Ethanol Exposure on Systemic Hemodynamic Variables and Histopathological Changes in the Aorta Wall of Male Rat Offspring: A Three-month Follow-up.

Background: Alcohol consumption in pregnancy is associated with an increased risk of cardiovascular abnormalities, but the mechanisms are unknown. This study evaluated the impact of ethanol exposure on the offspring’s aorta structural, functional, and molecular alterations on postnatal (PN) both on days 21 and 90.Methods:This experimental study was conducted at Urmia University of Medical Sciences (Urmia, Iran) in 2019. Twenty Pregnant Wistar rats on the seventh day of Gestation Day (GD) were randomly divided into two groups: control and ethanol-treated groups (n=10 per group). From the seventh day of GD throughout lactation, rats in the ethanol group were fed binge alcohol (4.5 g/Kg body weight) once daily. Systemic hemodynamic variables in the offspring were analyzed using waveform contour analysis 90 days after birth. On postnatal days (PN) 21 and 90, aorta wall histological alterations and the level of inflammatory factors were assessed in the aorta of male offspring. The statistical differences were examined via an independent samples t test. P<0.05 was considered to be statistically significant. Results: The results revealed that offspring in the ethanol group had higher systolic, diastolic, mean arterial pressure, and dicrotic pressure than the control group (P<0.001). The level of aorta tissue tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-κ, and endothelin-1 were significantly higher in the ethanol offspring group than in the control group (P<0.001). Histopathological changes such as total aorta thickness, tunica media, tunica adventitia, elastin fiber thickness, fiber interval, and elastin/media ratio significantly increased in the aorta of the offspring of the ethanol group compared to the control group 21 and 90 days after birth.Conclusion: Our findings suggest that prenatal and early postnatal ethanol exposure-induced cardiovascular abnormalities are, in part, due to predisposing the aorta to atherosclerosis, which was mediated through the aorta wall remodeling and inflammation process.

Prone ex vivo lung perfusion protects human lungs from reperfusion injury

We previously reported beneficial effects of prone positioning during ex vivo lung perfusion (EVLP) using porcine lungs. In this study, we sought to determine if prone positioning during EVLP was beneficial in human donor lungs rejected for clinical use. Human double lung blocs were randomized to prone EVLP (n=5) or supine EVLP (n=5). Following 16 h of cold storage at 4°C and 2h of cellular EVLP in either the prone or supine position. Lung function, compliance, and weight were evaluated and transplant suitability determined after 2h of EVLP. Human lungs treated with prone EVLP had significantly higher partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio [348 (291-402) vs. 199 (191-257) mm Hg, p=0.022] and significantly lower lung weight [926(864-1078) vs. 1277(1029-1483) g, p=0.037] after EVLP. 3/5 cases in the prone group were judged suitable for transplant after EVLP, while 0/5 cases in the supine group were suitable. When function of upper vs. lower lobes was evaluated, prone EVLP lungs showed similar P/F ratios and inflammatory cytokine levels in lower vs. upper lobes. In contrast, supine EVLP lungs showed significantly lower P/F ratios [68(59-150) vs. 467(407-515) mm Hg, p=0.012] and higher tissue tumor necrosis factor alpha levels [100.5 (46.9-108.3) vs. 39.9 (17.0-61.0) ng/ml, p=0.036] in lower vs. upper lobes. Prone lung positioning during EVLP may optimize the outcome of EVLP in human donor lungs, possibly by improving lower lobe function.

Paeoniflorin improves myocardial injury via inhibition of Src/VE-cadherin pathway in septic rats

Objective: To study the protective effect and mechanism of paeoniflorin (pae) on myocardial injury in septic rats. Methods: Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 rats in each group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml 5% dimethyl sulfoxide (DMSO)solution independently in control group and DMSO group. Rats were intraperitoneally injected with 1.4 ml normal saline and 1.4 ml pae independently, then with 0.1 ml lipopolysaccharide (LPS) 1 hour later in sepsis group and pae group. Enzyme linked immunosorbent assay (ELISA) was used to detect serum cardiac troponin I (cTnI) levels and myocardial tissue tumor necrosis factor alpha (TNFα), interleukin(IL)-6, IL-1β, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2), vascular cell adhesion molecule 1 (VCAM-1) levels. Evans blue (EB) method was used to detect the EB content of myocardial tissue. HE staining method was used to observe the pathological changes, real-time quantitative polymerase chain reaction (RT-qPCR) to detect mRNA expression levels of the above molecules, and Western-blot to detect vascular endothelium-cadherin (VE-cadherin), phosphorylated p38 mitogen-activated protein kinase (P-p38MAPK), phosphorylated Src protein (P-Src), Ras-Related C3 Botulinum Toxin Substrate 1 (Rac1) levels. Results: Compared with control group, cTnI level and the EB content in sepsis group increased significantly, and the myocardial inflammatory cell infiltration was obvious. The cTnI level and EB content in pae group were significantly reduced, and myocardial inflammatory cell infiltration was reduced [cTnI: (227.7±15.9)pg/ml vs. (312.9±17.9)pg/ml;EB: (13.2±2.3)μg/g vs. (23.8±2.9)μg/g; P<0.05]. Compared with control group, the levels of TNFα, IL-6, IL-1β, CXCL1, CXCL2, and VCAM-1 in sepsis group were increased. Compared with sepsis group, the above-mentioned molecular levels of pae group were significantly decreased [TNFα: (63.39±9.55)pg/ml vs. (126.54±19.17)pg/ml ;IL-6: (64.03±8.82)pg/ml vs. (85.60±9.52)pg/ml;IL-1β: (69.52±9.23)pg/ml vs. (130.45±15.10)pg/ml;CXCL1: (2 600.19±379.54)pg/ml vs. (4 903.89±533.42)pg/ml;CXCL2: (93.71±10.83)pg/ml vs. (127.24±13.92)pg/ml;VCAM-1: (112.22±13.49)pg/ml vs. (149.32±15.65)pg/ml, both P<0.05]. RT-qPCR results showed that the mRNA expressions of TNFα, IL-6, IL-1β, CXCL1, CXCL2 and VCAM-1 in the sepsis group were increased compared with the control group; Compared with sepsis group, the IL-6 mRNA (1.271±0.139 vs. 1.920±0.191, P<0.05), IL-1βmRNA (1.180±0.130 vs. 1.817±0.191, P<0.05), VCAM-1 mRNA (1.088±0.144 vs. 1.460±0.166, P<0.05) expression decreased significantly in the pae group. Compared with control group, the levels of P-p38MAPK and P-Src in sepsis group increased, and the level of VE-cadherin decreased. Compared with sepsis group, the levels of p38MAPK and P-p38MAPK in pae group were significantly decreased, and the level of VE-cadherin was increased (p38MAPK/β-actin: 1.125±0.078 vs. 1.520±0.164; P-p38MAPK protein: 1.639±0.133 vs. 2.112±0.222; both P<0.05). Conclusion: Paeoniflorin could improve the permeability of cardiac microvascular endothelium in sepsis rats and inhibit the secretion and expression of inflammation-related proteins and genes, which might be related to the inhibition of Src/VE-cadherin pathway by paeoniflorin.

Microvessel quantification by fully convolutional neural networks associated with type 2 inflammation in chronic rhinosinusitis

BackgroundThe pathogenesis of chronic rhinosinusitis (CRS) is still unclear, and little is known about angiogenesis in this disease. We utilized a fully convolutional network (FCN), which has been extensively used in image processing to study angiogenesis in CRS. ObjectiveTo explore the tissue quantification of microvessels and their potential association with inflammation in CRS by using FCN to reflect the angiogenesis condition in CRS. MethodsFor endotyping of CRS, tissue homogenates of 79 patients with CRS who had undergone functional endoscopic sinus surgery and 17 control subjects were analyzed for interferon gamma, transforming growth factor beta, interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha, eosinophilic cationic protein, immunoglobulin E, and Staphylococcus aureus-immunoglobulin E(SE-IgE). A total of 552 hematoxylin and eosin-stained images of 27 CRS tissue samples were used to develop an FCN, going through training, validation, and evaluation processes. An optimized FCN was applied to quantify the microvessels of tissue samples of all subjects. Correlation analysis between microvessel quantification with phenotype, endotype, clinical characteristics, and cytokine expression of CRS was carried out. ResultsQuantification of microvessels in type 2 and non-type 2 CRS demonstrated considerable differences, with a higher expression in type 2 CRS. There was a strong negative correlation between the area ratio of microvessels with tissue tumor necrosis factor alpha and transforming growth factor beta levels and a mildly positive correlation with tissue IL-5 and eosinophilic cationic protein concentration. ConclusionFCN proved to facilitate the analysis of microvessels in airway tissue samples. This study elucidated the close association of angiogenesis with endotyping, suggesting that treatment aiming at antagonizing angiogenesis may assist to the therapy for the recrudescent and refractory CRS.

Extraction and purification of oridonin from Rabdosia rubescens and its protective effect on intracerebral hemorrhage-induced brain injury in rats

Oridonin was extracted and purified from Rabdosia rubescens and its protective effect on intracerebral hemorrhage (ICH)-induced brain injury in rats was investigated. The rats were divided into sham, model, low-dose oridonin, middle-dose oridonin and high-dose oridonin groups. The ICH-induced brain injury model was established in latter four groups. After modeling, the low-, middle- and high-dose oridonin groups were treated with 10, 20, and 40 mg/kg oridonin at 2h and 24 h after modeling, respectively. Results showed that, after 48 after modeling, compared with model group, in middle- and high-dose oridonin groups the modified Neurological Severity Score was significantly decreased (P < 0.05), the brain water content was significantly decreased (P < 0.05), the brain tissue tumor necrosis factor α, interleukin 1β, interleukin 6 and nuclear factor-kappa B (NF-κB) p65 protein levels were significantly decreased (P < 0.05), and the brain tissue erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein levels were significantly increased (P < 0.05). In conclusion, oridonin from Rabdosia rubescens can mitigate the ICH-induced brain injury in rats. The mechanism may be related to its reduction of inflammatory response and oxidative stress by inhibiting NF-κB inflammatory pathway and promoting Nrf2/HO-1 antioxidant pathway in brain tissues.

Extraction of breviscapine from Erigeron breviscapus and its effect on oxidative stress, inflammation, energy metabolism disorder and apoptosis in rats with uterine ischemia-reperfusion injury

This work aimed to prepare breviscapine from Erigeron breviscapus and investigate its protection mechanism on uterine ischemia-reperfusion injury (UIRI) in rats. Breviscapine was extracted and separated from Erigeron breviscapus. Sixty female SD rats were randomly divided into sham-operated, model and breviscapine groups. The breviscapine group was treated with 5 mg/kg breviscapine for three days. Then, the UIRI model was established in model and breviscapine groups via uterine artery ischemia for 30 min followed by reperfusion for 60 min. At the end of reperfusion, compared with model group, in breviscapine group the uterine tissue superoxide dismutase activity was increased, and the malondialdehyde level was decreased; the uterine tissue tumor necrosis factor α, interleukin (IL)-1β and IL-6 levels were decreased, and the IL-10 level was increased; the uterine tissue adenosine triphosphate, adenosine diphosphate, adenosine monophosphate and total adenine nucleotides levels were increased; the uterine cell apoptosis rate was decreased, the Bcl-2 protein expression level was increased, and the Bax protein expression level was decreased. In conclusion, breviscapine from Erigeron breviscapus can reduce the oxidative stress, inflammatory reaction, energy metabolism disorder and apoptosis in uterine tissue, thus exerting the protective effect on UIRI in rats.

Effect of formononetin from Trifolium pratense L. on oxidative stress, energy metabolism and inflammatory response after cerebral ischemia-reperfusion injury in mice

Cerebral ischemia-reperfusion injury (CIRI) is one of the main diseases leading to death and disability. Studying the role and mechanism of drugs in mitigating CIRI is of great significance. In the present study, the effect of formononetin from Trifolium pratense L. on oxidative stress, energy metabolism impairment and inflammatory response after cerebral ischemia-reperfusion injury (CIRI) in mice were investigated. Formononetin was extracted from Trifolium pratense L. and was purified. The mice were treated with formononetin for six days. Then, the CIRI model was established. After 24 h of reperfusion, compared with model group, in formononetin group, the neurological deficit score, cerebral water content and cerebral infarction rate were significantly decreased, the brain tissue nitric oxide and malondialdehyde levels were significantly decreased, the brain tissue superoxide dismutase level was significantly increased, the brain tissue Na+-K+-ATPase, Ca2+-Mg2+-ATPase and Ca2+-ATPase activities were significantly increased, and the brain tissue tumor necrosis factor α, interleukin 1β and interleukin 6 levels were significantly decreased. In conclusion, formononetin from Trifolium pratense L. can reduce the oxidative stress, energy metabolism impairment and inflammatory response in brain tissues, thus mitigating the CIRI in mice.

Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats

Galangin is a natural flavonoid isolated from ginger, honey and propolis. Aims: To investigate the effect of galangin on blood pressure, vascular changes, sympathoexcitation, oxidative stress and inflammation in rats treated with NG-nitro-l-arginine methyl ester (l-NAME). Materials and methods: Male Wistar rats (220-250 g) were given l-NAME (0.5 mg/mL in drinking water) to induce hypertension for 5 weeks. They were treated with vehicle, galangin (30 or 60 mg/kg), or amlodipine (10 mg/kg) for the final two weeks (n = 6/group). Key findings: Galangin significantly reduced blood pressure and improved the impairment of endothelium-dependent vasodilation in hypertensive rats. Sympathoexcitation, including enhancement of contractile responses to electrical field stimulation, increases in intensity of tyrosine hydroxylase and plasma norepinephrine concentration in hypertensive rats, was attenuated by galangin treatment. Galangin also reduced systemic and vascular oxidative damage and increased plasma nitric oxide levels in the hypertensive groups. Aortic remodelling accompanied by aortic wall hypertrophy and fibrosis observed in hypertensive rats were alleviated by galangin treatment. Furthermore, galangin exhibited an anti-inflammatory effect by suppressing the upregulation of tumour necrosis factor receptor 1 (TNF-R1), phospho-nuclear factor kappa B (p-NF-κB) and vascular cell adhesion protein 1 (VCAM-1) in aortic tissue and reducing plasma tumour necrosis factor alpha (TNF-α) in l-NAME rats. In conclusion, galangin had antihypertensive effects that were relevant to attenuating endothelial dysfunction, sympathoexcitation and vascular remodelling. These effects might be contributed by antioxidant and anti-inflammatory capacities and modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.

Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2\u2013STAT3 pathway

Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling.

English

The aim of this study was to evaluate the effect of Berberis vulgaris water extract (BWE) against CCl4-induced hepatotoxicity and LPS/PCM induced- hepatic inflammation in the experimental animal models. CCl4 (100 ug/kg, oral) administration for 28 days as well as the co-administration of LPS (250 ug/kg bw) and PCM (2 g/kg bw) for 28 days resulted in massive elevation in serum and hepatic prooxidants and inflammatory parameters (thiobarbituric acid reactive substances (TBARS), tissue tumor necrosis factor&ndash;alpha (TNF-&alpha;), interleukin 6 (IL-6) and IL-12 and nitric oxide (NO) with depletion in antioxidants system (superoxide dismutase (SOD) and glutathione peroxidase (GPx). These alterations were combined with elevation of serum liver function tests (alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase level and (ALP). Oral administration of the BWE (100 mg/kg) for 15 days showed hepatoprotective and anti-inflammatory effects against both CCl4 and LPS/PCM as it increased the activities of antioxidants enzymes, decreased the prooxidants and inflammatory markers levels and improved the serum liver function tests levels. The obtained findings thus suggest that B. vulgaris aqueous extract has protective roles against hepatic toxicity and hepatic inflammation due to its antioxidant and anti-inflammatory properties. Key words: Carbon tetrachloride, paracetamol, lipopolysaccharide, glutathione peroxidase, alanine transferase.

Effects of Ganoderma lucidum Polysaccharides on Different Pathways Involved in the Development of Spinal Cord Ischemia Reperfusion Injury: Biochemical, Histopathologic, and Ultrastructural Analysis in a Rat Model

Inflammation and oxidative stress are 2 important factors in the emergence of paraplegia associated with spinal cord ischemia-reperfusion injury (SCIRI) after thoracoabdominal aortic surgery. Here it is aimed to investigate the effects of Ganoderma lucidum polysaccharide (GLPS) on SCIRI. Rats were randomly selected into 4 groups of 8 animals each: sham, ischemia, methylprednisolone, and GLPS. To research the impacts of various pathways that are efficacious in formation of SCIRI, tumor necrosis factor α, interleukin 1β, nitric oxide, superoxide dismutase levels, and catalase, glutathione peroxidase activities, malondialdehyde levels, and caspase-3 activity were measured in tissues taken from the spinal cord of rats in all groups killed 24 hours after ischemia reperfusion injury. The Basso, Beattie, and Bresnahan locomotor scale and inclined plane test were used for neurologic assessment before and after SCIRI. In addition, histologic and ultrastructural analyses of tissue samples in all groups were performed. SCIRI also caused marked increase in tissue tumor necrosis factor α, interleukin 1β, nitric oxide, malondialdehyde levels, and caspase-3 activity, because of inflammation, increased free radical generation, lipid peroxidation, and apoptosis, respectively. On the other hand, SCIRI caused significant reduction in tissue superoxide dismutase, glutathione peroxidase, and catalase activities. Pretreatment with GLPS likewise diminished the level of the spinal cord edema, inflammation, and tissue injury shown by pathologic and ultrastructural examination. Pretreatment with GLPS reversed all these biochemical changes and improved the altered neurologic status. These outcomes propose that pretreatment with GLPS prevents progression of SCIRI by alleviating inflammation, oxidation, and apoptosis.

Parecoxib mitigates lung ischemia-reperfusion injury in rats by reducing oxidative stress and inflammation and up-regulating HO-1 expression.

ABSTRACTPurpose:To investigate the protective effect of parecoxib against lung ischemia-reperfusion injury (LIRI) in rats and the mechanism.Methods:Thirty rats were divided into sham-operated, LIRI and LIRI+parecoxib groups. LIRI model (ischemia for 60 min, followed by reperfusion for 120 min) was constructed in LIRI and LIRI+parecoxib groups. In LIRI+parecoxib group, 10 mg/kg parecoxib was given via femoral vein 15 min before ischemia beginning. At the end of the reperfusion, blood gas analysis, lung wet to dry mass ratio measurement, lung tissue biochemical determination and heme oxygenase-1 (HO-1) protein expression determination were performed.Results:Compared with LIRI group, in LIRI+parecoxib group the oxygenation index was significantly increased, the alveolar-arterial oxygen partial pressure difference was significantly decreased, the lung wet to dry mass ratio was significantly decreased, the lung tissue malondialdehyde content was significantly decreased, the lung tissue superoxide dismutase and myeloperoxidase activities were significantly increased, the lung tissue tumor necrosis factor α and interleukin 1β levels were significantly decreased, and the lung tissue HO-1 protein expression level was significantly increased (all P < 0.05).Conclusions:Parecoxib pretreatment can mitigate the LIRI in rats by reducing oxidative stress, inhibiting inflammatory response and up-regulating HO-1 expression in lung tissue.

Preparation of long-acting microspheres loaded with octreotide for the treatment of portal hypertensive

The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 μm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI2) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA2), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.

Oleanolik asidin çekal ligasyon ve punksiyon ile sepsis oluşturulan ratlarda kalp hasarı üzerine etkileri

Bu çalışmada zeytin ağacı (Olea europeae) ağacının yaprağından saflaştırılan oleanolik asidin (OEA) ratlarda çekal ligasyon ve punksiyonla (CLP) indüklenen sepisisin oluşturduğu kalp hasarı üzerine etkileri incelendi. Her gruba eşit olacak şekilde 30 adet Wistar erkek rat sham, sepsis, OEA-150, OEA-300 ve CEFT olarak 5 gruba ayrıldı. Kromatografik metotlarla zeytin yaprağından saflaştırılan oleanolik asit OEA gruplarına 150 ve 300 mg/kg dozlarda oral yolla uygulandı. CEFT grubuna seftriakson 150 mg/kg dozda intraperitoneal yolla uygulandı. Uygulamadan 24 saat sonra ratlardan kan serumu ve kalp dokuları, histopatolojik, immünohistokimyasal ve biyokimyasal analizler için alındı. Yapılan histopatolojik ve immünohistokimyasal incelemede, sepsis grubunun doku tümör nekrozis faktör (TNF)- ve interlökin (IL)-1β ekspresyonlarında artış, myokartta kas liflerinde şiddetli düzeyde hyalin dejenerasyon, Zenker nekrozu ve damarlarda şiddetli düzeyde hiperemi gözlendi. OEA ve seftriakson (CEFT) sitokin ekspresyonlarında ve histopatolojik bulgularda azalma sağladı. Sepsis, doku superoksit dismutaz aktivitesini (SOD) azalttı. Ayrıca lipid peroksidasyonu (LPO) ve glutatyon (GSH) seviyeleri ile doku katalaz (KAT), serum kreatin kinaz (CK-MB) ve serum laktat dehidrojenaz (LDH) aktivitelerini önemli şekilde arttırdı. OEA ve CEFT, SOD aktivitesini önemli derecede arttırırken diğer parametrelerde belirgin düşüşe neden oldu. Bu çalışmadan elde edilen bulgular ışığında oleanolik asidin sepsis sırasında oluşan kalp dokusu hasarının azaltılmasında faydalı olabileceği düşünülmektedir.

The relationship of obesity and prostate cancer (review)

Obesity is a critical risk factor for prostate cancer (PCa). Adipose tissue plays an important role in tumor development, including growth, invasion, and metastasis. Diet and dietary components affect the progression of prostate cancer; however, the mechanisms underlying these associations remain unclear. Extraprostatic prostate tumor cells form a new microenvironment in the periprostatic adipose tissue, which alters these interactions and promotes tumor progression.&#x0D; Hyperinsulinemia leads to an increase in the level of free or biologically active insulin-like growth factor (IGF-1) due to a decrease in the production of IGF-binding proteins. Hypoandrogenism promotes the development of a more aggressive type of prostate cancer (higher Gleason scores). Adipokines of adipose tissue and cytokines (for example, interleukin-6 (IL-6) and tumor necrosis factor (TNF-), angiogenic factors (for example, vascular endothelial growth factor (VEGF), apelin (AGTRL1) and other factors (for example, leptin and adiponectin) have multiple effects on prostate cancer cells. Tumor cells interact directly or indirectly with adipocytes.&#x0D; Yellow (inactive) bone marrow is adipose tissue with separate islands of reticular tissue. It is located in the medullary canals of the tubular bones and in parts of the cells of the cancellous bone. Bone tissue is the object of the most frequent metastasis in prostate cancer, and with age, the content of fat cells in it increases. Bone marrow adipose tissue interacts with tumor cells, osteoblasts and other stromal cells and participates in the organization of the tumor microenvironment. Adipokines are key molecules in the interaction between tumor cells and adipose tissue, which is carried out through various mechanisms. A better understanding of the role of adipose tissue in the induction and progression of prostate cancer will lead to effective therapeutic strategies for this disease.

The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A3 Receptor Agonist, in a Rat Model of Colitis.

The pharmacological activation of A3 receptors has shown potential usefulness in the management of bowel inflammation. However, the role of these receptors in the control of visceral hypersensitivity in the presence of intestinal inflammation has not been investigated. The effects of AR170, a potent and selective A3 receptor agonist, and dexamethasone (DEX) were tested in rats with 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis to assess their tissue inflammatory parameters. The animals received AR170, DEX, or a vehicle intraperitoneally for 6 days, starting 1 day before the induction of colitis. Visceral pain was assessed by recording the abdominal responses to colorectal distension in animals with colitis. Colitis was associated with a decrease in body weight and an increase in spleen weight. The macroscopic damage score and tissue tumor necrosis factor (TNF), interleukin 1β (IL-1β), and myeloperoxidase (MPO) levels were also enhanced. AR170, but not DEX, improved body weight. Both drugs counteracted the increase in spleen weight, ameliorated macroscopic colonic damage, and decreased TNF, IL-1β, and MPO tissue levels. The enhanced visceromotor response (VMR) in rats with colitis was decreased via AR170 administration. In rats with colitis, AR170 counteracted colonic inflammatory cell infiltration and decreased pro-inflammatory cytokine levels, thereby relieving visceral hypersensitivity.

The efficacy of adalimumab on experimentally induced spinal cord ischemia-reperfusion injury

Objective: Paraplegia is a dangerous complication of thoracoabdominal aortic surgery. Various studies have been conducted on the prevention of this complication and some spinal cord protection methods have been proposed. However, there is not any modality that prevent the development of paraplegia certainly. In the I / R period, primary injury triggers secondary injury due to increased inflammation, apoptosis and free radical formation. In this study, we evaluated that the neuroprotective effect of adalimumab in spinal cord ischemia-reperfusion injury. &#x0D; Materials and Methods: In total, 24 adult New Zealand rabbits were divided into three groups: Group 1, control; Group 2, ischemia-reperfusion by infrarenal aortic clamping; Group 3, adalimumab treated followed by ischemia. Tissue and plasma tumor necrosis factor alpha, interleukin 6, interleukin 10, thiobarbituric acid reactive substance, total oxidant status and total antioxidant status levels were analyzed as a marker of inflammation and oxidation. Histopathological evaluation of the tissues was performed, and apoptosis was evaluated by TUNNEL method.&#x0D; Results: I/R injury significantly increases plasma and spinal cord tissue at TNF alpha, TOS, TBARS, IL6 levels and reduces plasma and spinal cord tissue to TAS and IL10 levels. Adalimumab treatment significantly reduces plasma and spinal cord tissue to TNF alpha, TOS, TBARS, IL6 and increases plasma and tissue to TAS and IL10 levels.&#x0D; Conclusion: Adalimumab treatment significantly reduces the spinal cord neuronal damage score and the number of apoptotic cells. This paper aims to demonstrate the important neuroprotective effects of adalimumab on rabbit spinal cord I/R injury.