Serum Levels Of Interleukin-1β Research Articles

Daily interleukin-1β variability in women with rheumatoid arthritis associated with fibromyalgia

Annotation. Disorders of circadian rhythms are considered to be one of the factors associated with the development of joint diseases. In patients with rheumatoid arthritis (RA) disorders of the neurohumoral regulation of circadian rhythms is a factor in the increased production of inflammatory cytokines in the joint tissues. In 30 % of RA patients, concomitant fibromyalgia (FM) is found, in which disorders of circadian regulation can deepen. Circadian features of the production of pain mediators and inflammation in RA patients with comorbid fibromyalgia (FM) have not been established. The aim of this study was to investigate the daily variability of serum interleukin-1β levels in RA patients depending on the comorbidity of FM. Materials and methods: 49 patients with rheumatoid arthritis (RA) (100 % female) aged 46.8 (39–53) years, with moderate and high disease activity (DAS28>3.2), of which 21 (42.9 %) patients with concomitant fibromyalgia (FM). Diagnosis of RA was established by ACR/EULAR criteria (2010), FM was diagnosed by mACR 2010. Blood sampling was performed twice daily (at 08-00 and at 20-00), the level of IL-1β in the blood was determined by enzyme immunoassay. The studies were conducted according to bioethical standards. Statistical processing of the results was performed by SPSS Statistics 22.0. Results: In RA patients circadian fluctuations of IL-1β level in blood were registered. IL-1β levels (08-00) in the morning was higher (1.2–1.3 times) than in the evening (20-00). In the presence of comorbid FM, patients with RA had significant increase in evening and average daily levels of IL-1β (1.3–1.6 times) than in RA patients without FM. Daily fluctuations of IL-1β correlate with RA activity and the fibromyalgia scale. Conclusions: In RA patients disorders of the circadian production of proinflammatory IL-1β, which are exacerbated under FM conditions, were detected. Increasing evening production of IL-1β correlated with the prevalence of pain index in RA patients with FM. Thus, disorders of IL-1β circadian production in RA patients can be integrated into the mechanisms of central sensitization and FM development.

PSIX-9 Dietary β-sitosterol improves immunity and antioxidant status in broilers

Abstract The application effects of phytosterols on poultry production have been reported. However, due to the mixed compositions, it is difficult to explain their action mode and physiological functions. β-sitosterol, the most abundant phytosterol, is naturally widespread in plant products. Information, however, is scarce in terms of effects of β-sitosterol on broilers. This research therefore investigated effects of dietary β-sitosterol with different levels on immunity and antioxidant capacity in broilers. Two hundred and forty one-day-old chicks were randomly allocated into five treatments of six replicates. Chickens in the five groups were fed a basal diet supplemented with 0 (control group), 40, 60, 80, and 100 mg/kg β-sitesterol for 42 days, respectively. Data were analyzed by one-way analysis of variance. Polynomial contrasts were used to test the linear and quadratic response to β-sitosterol levels. Difference among groups was evaluated using Tukey’s test, which was considered significant if P < 0.05. Dietary β-sitosterol linearly increased (P < 0.05) contents of serum immunoglobulin G and hepatic glutathione, activities of serum superoxide dismutase and catalase, whereas linearly decreased (P < 0.05) concentrations of serum tumor necrosis factor α and hepatic malondialdehyde. Serum interleukin 1β level was linearly and quadratically reduced by β-sitosterol inclusion (P < 0.05). Compared with the control group, dietary β-sitosterol with higher levels than 60 mg/kg increased concentrations of serum immunoglobulin G and hepatic glutathione, activities of serum superoxide dismutase and catalase (P < 0.05), whereas decreased serum tumor necrosis factor α content (P < 0.05). Its dosages higher than 40 mg/kg reduced serum interleukin 1β content (P < 0.05), and 100 mg/kg of which lowered hepatic malondialdehyde concentration (P < 0.05). The results indicated that dietary β-sitosterol could improve immunity and antioxidant ability in broilers. Also, a level of 80 mg/kg β-sitosterol supplementation was recommended into broiler diet.

Effects of IL-1β and IL-18 induced by NLRP3 inflammasome activation on myocardial reperfusion injury after PCI.

To investigate the effect of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in patients with myocardial reperfusion injury after the percutaneous coronary intervention (PCI). Twenty healthy controls (control group) and forty patients (treatment group) were recruited in this study. The enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IL-1β and IL-18 at various time points in both the control and treatment groups. Data processing and analysis were performed using the Statistical Product and Service Solution (SPSS) 22.0 software (IBM Corp, Armonk, NY, USA). Pearson's correlation coefficient test was applied in all data analyses. A difference was statistically significant when p<0.05. The levels of IL-1β and IL-18 in the treatment group were significantly higher than those in the control group (p<0.05). The IL-1β level in the treatment group peaked at 0.5 h after PCI and then, gradually decreased. The multiple regression analysis showed that IL-1β level was positively correlated with levels of LDL-C and IL-18 (p<0.05, r=0.527 and 0.955 respectively), and negatively correlated with the HDL-C level (p<0.05, r=-0.34). The levels of IL-1β and IL-18 significantly rose in patients with myocardial ischemia-reperfusion injury after PCI.

Knee muscle atrophy is a risk factor for development of knee osteoarthritis in a rat model

ObjectivesThe objective of this study was to investigate the effect of botulinum toxin type A (BTX-A)–induced quadriceps muscle atrophy on the cartilage and subchondral bone in an otherwise intact rat joint model. MethodsThe rat right quadriceps muscle atrophy was established by intramuscular injection of BTX-A. Twenty-four rats were divided randomly into 3 groups: The BTX-A–treated 4-week group; the BTX-A–treated 8-week group; and the control group injected with phosphate buffer saline were observed for 8 weeks. Muscle atrophy level was measured by weighing and histology examinations. Serum interleukin-1β level was tested by ELISA (enzyme linked immunosorbent assay); the subchondral bone was analysed by micro–computed tomography and the cartilage was measured by histology examinations (gross view, haematoxylin and eosin staining and Safranin-O/fast green staining) and immunohistochemistry test {collagen X [ColX]}. ResultsBTX-A intramuscular injection led to muscle atrophy. Characteristics of muscle atrophy appeared in two BTX-A–injected groups but not in the control group. Quadriceps atrophy did not affect interleukin-1β level in serum, but resulted in subchondral bone abnormal changes with reduced bone volume/total tissue volume ​and increased Structure Model Index. Furthermore, the more the severe cartilage damage, the higher the histologic damage scores, followed by the higher the percentage of collagen X–positive chondrocytes caused by muscle atrophy. ConclusionsQuadriceps muscle atrophy triggered the subchondral bone abnormal change and cartilage degeneration, which would be a risk factor for development of osteoarthritis. The translational potential of this articleOur results indicate that anti-quadriceps muscle atrophy can be a candidate therapeutic target in the prevention of knee osteoarthritis.

Chungkookjang, a soy food, fermented with Bacillus amyloliquefaciens protects gerbils against ishcmeic stroke injury, and post-stroke hyperglycemia.

Chungkookjang is a traditional Korean fermented soybean food with anti-diabetic and thrombolytic activity. It may also have anti-stroke activity. We determined that chungkookjang made with Sunchang Research Center for Fermentation Microbes 100730 and 100731 strains of Bacillus amyloliquefaciens(SRCM100730; CKJ730) and SRCM100731(CKJ731) protected against ischemic stroke and post-stroke hyperglycemia in Mongolian gerbils with ischemic stroke induced by transient occlusion of the carotid arteries. Gerbil fed 4.5% cooked soybeans (CSB), CKJ730, CKJ731, or cellulose (negative-control) in 40 energy% fat diets for 3 weeks, and then had artery occlusion for 8 min and continued taking the assigned diet for 5 weeks. CKJ730 and CKJ731 had thrombolytic activity and prevented neuronal cell death. Consequently, they improved short-term memory and spontaneous alteration compared to the negative-control. CKJ730 and CKJ731 improved neurological symptoms including drooped eyes, crouched posture, flexor reflex, and walking patterns the most among the stroke-induced gerbils. CKJ730 and CKJ731 increased active time, grip strength, and blood flow measured by Doppler compared to the negative-control. CKJ730 protected against post-stroke glucose dysregulation by restoring β-cell mass in the gerbils with transient artery occlusion. Serum tumor necrosis factor-α and interleukin-1β levels were lower in CKJ730 and CKJ731 than the negative-control. CSB also improved glucose metabolism and suppressed inflammatory cytokines, but less than CKJ730 and CKJ731. Clostridia increased, and Bacteriodia slightly decreased in the negative-control group, compared to the normal-control. CKJ730 and CKJ731 changed the amounts of Bacteriodia and Clostridia to be similar to normal-control. In conclusion, the daily intake of chungkookjang fermented with B. amyloliquefaciens improved the gut microbiome, increased blood flow to the brain, suppressed systemic inflammation, and may reduce the susceptibility to injury from ischemic stroke in gerbils subjected to ischemic injury.

Low-dose alcohol ameliorated homocysteine-induced anxiety-related behavior via attenuating oxidative stress in mice

Recent studies showed that homocysteine (Hcy) levels were obviously elevated in patients with anxiety, furthermore, oxidative stress and inflammation were closely linked with Hcy-related damage. Despite alcohol exposure has differential effects on different forms of anxiety, the role of alcohol on anxiety-related behavior induced by high Hcy levels is still not entirely clear. The present study investigated the protective potential of low-dose alcohol against homocysteine-induced anxiety-related behavior and explored the possible underlying mechanisms. Mice were administered intragastrically with methionine (2.0 g/kg/day) or alcohol (0.6 g/kg/day). After 21 days of administration, the anxiety-related behavior was evaluated through open field (OF) and elevated plus maze (EPM) tests, and the variations of oxidative stress and inflammation levels were measured. The results of OF and EPM tests showed that the anxiety-related behavior in mice was prevented by alcohol treatment. Alcohol lowered the elevated serum Hcy levels and alleviated the damage of hippocampal tissues in hyperhomocysteinemia (HHcy) mice. Meanwhile, the superoxide dismutase (SOD) activity of the hippocampal tissues enhanced, and the malondialdehyde (MDA) concentration of the hippocampal tissues and the serum interleukin-1β (IL-1β) level decreased. In addition, after administering alcohol, the increase of superoxide dismutase 1 (SOD1), heme oxygenase 1 (HO-1) protein expression and the decrease of IL-1β protein expression were also detected in HHcy mice hippocampal tissues. Taken together, low-dose alcohol significantly ameliorated the Hcy-induced anxiety-related behavior in mice, which might be related to SOD1 and HO-1 upregulation and IL-1β downregulation.

Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin.

Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway

BackgroundWhitmania pigra Whitman (W pigra), a traditional Chinese medicine, has functions of breaking stagnant and eliminating blood stasis. The aim of this study was to investigate the underlying mechanism of W pigra against deep vein thrombosis (DVT). MethodsA rat model of DVT induced by inferior vena cava stenosis was successfully established. Rats were administered vehicle (saline solution, p.o.), three doses of W pigra aqueous extract (34.7, 104.2, or 312.5 mg crude W pigra/kg, p.o.), heparin (200 U/kg, i.v.), or clopidogrel (25 mg/kg, p.o.) once daily for 2 d. Thrombus weight and histopathological changes were examined. Blood samples were collected to determine blood cell counts, blood viscosity, blood coagulation, blood fibrinolysis, serum levels of interleukin-1β, and tumor necrosis factor-α. Protein expressions of Sirtuin1 (SIRT1), acetylated p65 (Ace-p65), and phosphorylated p65 (p-p65) were determined by Western blot. Furthermore, SIRT1-specific inhibitor EX527 was applied to confirm the role of SIRT1 in the antithrombotic effect of W pigra. ResultsW pigra significantly decreased thrombus weight. W pigra had no effects on blood cell counts, whole blood viscosity, blood coagulation, blood fibrinolysis. However, it reduced tissue factor protein expression in the vein wall and thrombus. Moreover, it sharply increased SIRT1 protein expression and decreased leukocytes recruitment in the thrombus and vein wall, serum levels of interleukin-1β and tumor necrosis factor-α, and protein expressions of Ace-p65 and p-p65. Furthermore, the antithrombotic effect of W pigra was significantly abolished by EX527. ConclusionsAqueous extract of W pigra effectively reduced DVT burden by inhibiting inflammation via SIRT1/nuclear factor-kappa B signaling pathway.

The effect of minocycline on amelioration of cognitive deficits and pro-inflammatory cytokines levels in patients with schizophrenia

BackgroundCognitive deficits of schizophrenia are predictors of poor function, but antipsychotic medication has limited efficacy for cognitive deficits. These deficits in learning and memory may result from activity of pro-inflammatory cytokines, which microglia produce. The microglia inhibitor minocycline might arrest this cytokine damage to the hippocampus and reverse the cognitive deficits of schizophrenia. MethodsA double-blind, placebo-controlled study involved 75 patients with schizophrenia who randomly received low dose (100 mg/day) or high dose minocycline (200 mg/day) or placebo added to risperidone. MATRICS Consensus Cognitive Battery (MCCB) was used to assess the cognitive functioning, and serum levels of Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor–α (TNF-α) were assessed. ResultsMinocyclinehigh dose group was significantly superior to minocyclinelow dose or placebo group not only for the improvements in cognitive tests' scores as well (P < 0.05), but for IL-1β and IL-6 serum levels reduction (P < 0.01). The amelioration of cognitive deficits with minocycline correlated not only with the remission of negative symptoms, but also with the reduction in serum levels of IL-1β and IL-6. ConclusionsMinocycline adjunctive treatment was effective in improving cognitive deficits of patients with schizophrenia. The beneficial effect of minocycline may be related to reducing pro-inflammatory cytokines through microglia inhibition.

Effects of supplemented culture media from solid-state fermented Isaria cicadae on performance, serum biochemical parameters, serum immune indexes, antioxidant capacity and meat quality of broiler chickens.

ObjectiveThe objective of this study was to investigate effects of supplementation of culture media from solid-state fermented Isaria cicadae (I. cicadae) on performance, serum biochemical parameters, serum immune indexes, antioxidant capacity and meat quality of broiler chickens.MethodsA total of 648 Arbor Acres male broiler chickens(1 d; average body weight, 42.93± 0.47 g) were randomly assigned to 6 treatments, each with six replicates and 18 broiler chickens per replicate. Broiler chickens were fed phase I (d 1 to 21) and phase II (d 22 to 42) diets. The phase I diets were corn and soybean-meal based diets supplemented with 0%, 2%, 4%, 6%, 8%, or 10% culture media from solid-state fermented I. cicadae respectively. The phase II diets were corn and soybean-meal based diets supplemented with 0%, 1.33%, 2.67%, 4.00%, 5.32%, or 6.67% culture media from solid-state fermented I. cicadae respectively.ResultsIn phase I, the broiler chickens with the supplementation of culture media had increased body weight gain and feed intake (linear and quadratic, p<0.05) with increasing inclusion of culture media. The levels of serum total antioxidant capacity (T-AOC), glutathione (GSH) and superoxide dismutase (SOD) increased linearly (p<0.05). In phase II, levels of serum T-AOC and interleukin-1β increased linearly (p<0.05), and GSH increased (p<0.05). In the kidney, GSH and glutathione peroxidase (GSH-Px) concentrations increased (linear and quadratic, p<0.05) and SOD concentration increased linearly (p<0.05). Compared to the control, shear force and drip loss of breast muscle decreased (linear and quadratic, p< 0.05). Drip loss of leg muscle decreased linearly and quadratically (p<0.05).ConclusionDietary supplementation of culture media from solid-state fermented I.cicadae which was enriched in both wheat and residual bioactive components of I. cicadae enhanced the growth performance of broiler chickens. It also improved body anti-oxidative status and contributed to improve broiler meat quality.

Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy via MAPK pathway.

To investigate the effect of melatonin on diabetic retinopathy rats through the mitogen-activated protein kinase (MAPK) pathway. A total of 48 Sprague Dawley (SD) rats were randomly divided into normal group (n=12), model group (n=12), melatonin group (n=12), and inhibitor group (n=12). The rats in normal group received no treatment. Those in model group, melatonin group, and inhibitor group were prepared into models of diabetic retinopathy and intraperitoneally injected with normal saline, melatonin, and SB 203580, respectively. After 7 days of intervention, the materials were taken. The expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected through immunohistochemistry. Western blotting was employed to determine the protein expression levels of p38 MAPK, phosphorylated (p)-p38 MAPK, and cysteinyl aspartate specific proteinase-3 (Caspase-3). The messenger ribonucleic acid (mRNA) expression levels of Bax and Bcl-2 were measured via quantitative Polymerase Chain Reaction (qPCR). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of serum interleukin-1β (IL-1β) and IL-18. The apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL). Based on immunohistochemistry, model group, melatonin group, and inhibitor group exhibited significantly increased positive expression of Bax but notably decreased positive expression of Bcl-2 in comparison with normal group (p<0.05). Compared with those in model group, the positive expression of Bax was clearly reduced, while the positive expression of Bcl-2 was overtly raised in melatonin group and inhibitor group (p<0.05). The results of Western blotting showed that there was no difference in the protein expression of p38 MAPK among all groups (p>0.05). Compared with normal group, the other three groups had remarkably elevated protein expressions of p-p38 MAPK and Caspase-3 (p<0.05). The protein expressions of p-p38 MAPK and Caspase-3 in melatonin group and inhibitor group were significantly lower than those in model group decreased (p<0.05). QPCR assay revealed that the mRNA expression of Bax was markedly lower in normal group than that in the other three groups, while the mRNA expression of Bcl-2 was significantly higher in normal group than that in the other three groups (p<0.05). Compared with model group, melatonin group, and inhibitory group showed clearly declined mRNA expression level of Bax and notably increased mRNA expression level of Bcl-2 (p<0.05). TUNEL results revealed that the apoptosis rate was remarkably elevated in the other three groups compared with that in normal group (p<0.05). In comparison with model group, melatonin group and inhibitor group exhibited significantly reduced apoptosis rate (p<0.05). Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy by repressing the MAPK pathway.

Experimental study on the mechanism of glycogen synthase kinase-3β inhibitor on acute kidney injury of acute necrotizing pancreatitis in rats

To explore the protective mechanism of glycogen synthase kinase-3β (GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-ΚBp65 (NF-ΚBp65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-ΚBp65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L): 195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-ΚBp65 in the nucleus was significantly decreased; the expression of p-GSK-3β (Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Blockade of GSK-3β activity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-ΚB and its related inflammatory mediators.

Therapeutic effects of caffeic acid phenethyl ester on alveolar bone loss in rats with endotoxin-induced periodontitis

Background/purposeCaffeic acid phenethyl ester (CAPE) is an antioxidant which is decreases the bone resorption and enhances the bone healing. The aim of this study was to investigate the effects of administering systemic CAPE on alveolar bone loss in rats with experimental periodontitis. Materials and methodsThirty male Sprague Dawley rats were divided into three groups: control, endotoxin-induced periodontitis (EP), and EP treated with CAPE (EP-CAPE). Endotoxin was injected into the gingiva of test rats on days 1, 3, and 5, whereas saline was injected into the control rats. The EP-CAPE group received 10 mmol/kg/day CAPE intraperitoneally for 28 consecutive days. Saline was given in the control and EP groups in the same manner. At the end of the study, intracardiac blood samples were obtained, and the rats were sacrificed. Alveolar bone loss was analyzed with histometric measurements. The oxidative stress index (OSI) was used to evaluate the oxidative stress. The receptor activator of the nuclear factor kappa B ligand (RANKL) level was analyzed stereologically. ResultsCAPE administration significantly decreased the serum OSI and interleukin-1β levels. Alveolar bone loss was statistically higher in the EP group compared with the EP-CAPE group (P < 0.05). Immunohistochemical analyses of the RANKL were significantly lower in the EP-CAPE group than in the EP group (P < 0.05). ConclusionThis experimental study revealed that CAPE administration significantly prevented alveolar bone loss and stimulated periodontal tissue healing.

Analgesic and anti-inflammatory effects and molecular mechanisms of Kadsura heteroclita stems, an anti-arthritic Chinese Tujia ethnomedicinal herb

Ethnopharmacological relevanceRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by failure of spontaneous resolution of inflammation. The stem of Kadsura heteroclite (KHS) is a well-known anti-arthritic Tujia ethnomedicinal plant, which named Xuetong in folk, has long been used for the prevention and treatment of rheumatic and arthritic diseases. Aim of the studyThe analgesic and anti-inflammatory effects and the potential mechanisms behind such effects of KHS would be investigated by using different animal models. Materials and methodsThe abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid and the tail-flick response induced by radiant heat stimulation were used to evaluate the analgesic effect of KHS. The number of abdominal writhing episodes of mice and the latency of tail-flick in rats were measured and recorded. In acute inflammatory models, the ear edema of mice was induced by applying xylene on the ear surface, while the paw edema of male and female rats was induced by subcutaneous injection of carrageenan into the right hind paws of animals. The carrageenan-induced paw swelling in rats were selected as an anti-acute inflammatory mechanism of KHS. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were measured by ELISA, and protein expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by Western blot. ResultsThe maximal tolerated single dose of KHS was determined to be 26 g/kg in both sexes of mice. Pharmacological studies showed that KHS at the dose of 200 mg/kg significantly prolonged the reaction time of rats to radiant heat stimulation and suppressed abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid. KHS at the dose of 200, 400, and 800 mg/kg, showed dose-dependent inhibition of xylene-induced ear swelling in mice. KHS at the dose of 100, 200, 400, and 800 mg/kg demonstrated dose- and time-dependent suppression of paw edema induced by subcutaneous injection of carrageenan in both all rats. Mechanistic studies revealed that the anti-inflammatory effect of KHS was associated with inhibition of the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α and effectively decreased the expression of COX and iNOS proteins in the carrageenan-injected rat serum, paw tissues and inflammatory exudates. The positive reference drug, rotundine at a dosage of 100 mg/kg and indomethacin at a dosage of 10 mg/kg were used in both mice and rat models. ConclusionThese results suggested that KHS has significant effects on analgesia and anti-inflammation with decreasing the pro-inflammation cytokines of IL-1β, IL-6, and TNF-α and inhibiting the proteins expression of COX-2 and iNOS.

The interplay between microbiota‐dependent metabolite trimethylamine N‐oxide, Transforming growth factor β/SMAD signaling and inflammasome activation in chronic kidney disease patients: A new mechanistic perspective

Chronic kidney disease (CKD) signifies a frequently life-threatening condition influencing kidney structure and function. Despite its irrefutable importance, its exact pathogenesis is not completely clarified. However, CKD is known to be associated with accumulated uremic toxins/metabolites, interstitial fibrosis, and systemic inflammation. So we aimed to investigate the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO), transforming growth factor β (TGFβ)/SMAD signaling, and inflammasome activation in CKD pathogenesis through its different stages. Eighty patients with CKD of stages 2 to 4 in addition 15 healthy control subjects were enrolled. SMAD3 and nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) messenger RNA (mRNA) expressions from whole blood were assessed by quantitative real-time polymerase chain reaction (RT-PCR). Serum TGF-β1 and interleukin-1β (IL-1β) levels were estimated by the enzyme-linked immunosorbent assay. Plasma and urinary TMAO levels were measured. Oxidative stress markers were also assessed. SMAD3 and NLRP3 mRNA expressions were significantly upregulated in patients with CKD. Likewise, serum TGF-β1 and IL-1β levels were significantly elevated in patients with CKD, with increase in plasma and urinary TMAO levels and altered redox status throughout different CKD stages. The study documented that TMAO could be used as a reliable biomarker to evaluate CKD progression; being linked to TGF-β/SMAD signaling, NLRP3 inflammasome activation as well as being a noninvasive applicable technique.

MiR-146a regulates the development of ulcerative colitis via mediating the TLR4/MyD88/NF-κB signaling pathway.

To study the effect of micro ribonucleic acid (miR)-146a on the development of ulcerative colitis (UC) and to explore its regulatory effect on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB) signaling pathways. The UC model in rats was established using 2,4,6-trinitrobenzenesulfonic acid (TNBS)/ethanol. A total of 30 male rats were randomly divided into control group, model group and miR-146a inhibitor group, with 10 rats in each group. The disease activity index (DAI) and the macroscopic score of colonic mucosa were measured in each rat. MiR-146a expression in rat intestinal tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rats were detected via enzyme-linked immunosorbent assay (ELISA). Additionally, Western blotting assay was performed to detect protein levels of TLR4, MyD88, and NF-κB in rat intestinal tissues. Compared with those in control group, rats in model group had notably increased DAI, inflammation score, upregulated expression levels of TLR4, MyD88, NF-κB, and miR-146a, as well as increased serum levels of IL-1β and TNF-α. However, rats in miR-146a inhibitor group exhibited substantially decreased DAI, inflammation score, lowered content of IL-1β and TNF-α and levels of TLR4, MyD88, and NF-κB compared with those in model group. We found that miR-146a inhibitor alleviates UC by reducing the release of inflammatory factors through suppressing the TLR4/MyD88/NF-κB signaling pathway.

The study of oxidative status in children with end stage renal disease on regular hemodialysis

Background: Oxidative stress has long been demonstrated in haemodialysis patients. However, the factors influencing their oxidative status have not been characterized extensively in these patients. Despite heterogeneity in the oxidative stress levels in the CKD population, there has been little effort to measure patient oxidative stress levels before the use of any anti-oxidant therapies to optimize outcome. Objectives: Assessment of oxidative stress and the effects of using antioxidant medications on oxidative status in children with end stage renal disease under regular hemodialysis. Subjects and Methods: 70 children were included in this study and were categorized into 2 groups: Group (1): 35 children with ESRD on regular haemodialysis. Their ages ranged from 8 to 15 years old. They were 14 males and 21 females. All patients were undergoing haemodialysis three times per week, with each dialysis session lasting for three to four hours. Group (2): 35 healthy children with matched age and sex that were serving as control group. All patients were receiving antioxidant drugs regularly for 3 months. These antioxidant drugs were vitamin E in a dose of 5 mg/kg/day, vitamin C in a dose of 100-200 mg /day, N-Acetyl Cysteine in a dose of one sachet (200 mg) twice daily with meal. All children in both groups were subjected to: (a) complete history taking. (b) Full clinical examination. (c) Laboratory Investigations [Routine Investigations: CBC, blood urea, serum creatinine and BUN, PTH and PT, PTT and Bleeding Time. Specific Investigations: Measuring levels of 1-Interleukin-1β, tumor necrosis factor alpha, thiobarbituric acid reactive substances and malondialdehyde]. Results: There was an increase in markers of oxidative stress in children with end-stage renal disease on regular haemodialysis in the form of: 1) Increase serum level of interleukin 1β (IL-1β). 2) Increase serum level of tumor necrosis factor alpha (TNF-α). 3) Increase serum level of thiobarbituric acid reactive substances (TBARS). 4) Increase serum level of malondialdehyde (MDA). These levels were decreased with antioxidant drugs used in this study. Conclusion: The high levels of oxidative stress markers were decreased after regular therapy by antioxidant medications for 3 months in the form of vitamin E (5 mg/kg/day), vitamin C (100-200 mg /day) and N-Acetyl Cysteine (one sachet (200 mg) twice daily with meal).

Changes in insulin resistance and inflammatory factors in cataract patients with glaucoma after phacoemulsification and trabeculectomy: a self-controlled trial

Background and objective: Cataract with glaucoma can adversely affect visual acuity and corneal endothelial cells. Studies have shown that after phacoemulsification combined with trabeculectomy in patients with cataract and glaucoma, blood lipid ratio and insulin sensitivity are associated with intraocular pressure, visual acuity and corneal endothelial cells, which may be used for the evaluation of efficacy. Interleukins are the main mediators of the inflammatory response and are involved in the pathogenesis of cataract. In this trial, we will examine the postoperative changes in interleukin-10, interleukin-2 and interleukin-1β levels in patients with cataract with glaucoma, and analyze the correlation between insulin sensitivity and corneal endothelial cell density to assess whether inflammatory factors can be used to evaluate efficacy. Participants and methods: This prospective, single-center, open-label, self-controlled clinical trial will include 160 patients with cataract combined with glaucoma, 35–65 years of age, from the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, China. All patients will receive phacoemulsification and trabeculectomy, and will be followed up at 5 days, and at 1 and 3 months. Patient recruitment will begin on December 30, 2019 and end on December 30, 2020. Analysis of the results will be performed from May 1, 2021 to May 30, 2021. This study is scheduled to end on June 30, 2021. This study was approved by the Medical Ethics Committee, First Affiliated Hospital of Kunming Medical University, China, on December 15, 2013 (approval No. 20131215085), and will be performed in accordance with the principles of the Declaration of Helsinki, adopted by the World Medical Association. Study protocol version is 1.0. Written informed consent to participate will be obtained from each participant. Results: The primary outcome measure will be serum interleukin-2 level, as an index of the inflammatory response, 3 months after surgery. Secondary outcome measures will include serum interleukin-2 level before and 5 days and 1 month after surgery, serum levels of interleukin-1β, interleukin-10, C-reactive protein and tumor necrosis factor-α, best corrected visual acuity, endothelial cell density, mean cell area, coefficient of variation, insulin sensitivity index and intraocular pressure before and 5 days and 1 and 3 months after surgery, and incidence of adverse reactions at 5 days and 1 and 3 months after surgery. From January 2014 to June 2017, our team undertook and completed a small-sample study of 80 cataract patients (95 eyes) with glaucoma. The best corrected visual acuity was significantly improved, endothelial cell density and intraocular pressure were significantly reduced, interleukin-1β, interleukin-2, interleukin-10, C-reactive protein and tumor necrosis factor-α levels were significantly decreased (P Conclusion: The trial will confirm whether phacoemulsification combined with trabeculectomy has a good therapeutic effect in patients with cataract combined with glaucoma, and clarify whether the effect is associated with the regulation of insulin sensitivity index, corneal endothelial cells and inflammatory factors. Trial registration: This study was registered with the Chinese Clinical Trial Registry on September 10, 2019 (registration number: ChiCTR1900025837).

Protective effect of Traditional Chinese medicine Shuangwu Zhentong Capsule on collagen-induced arthritis in rats and possible mechanisms

The aim of this study was to investigate the protective effect of Traditional Chinese medicine Shuangwu Zhentong Capsule (SZC) on collagen-induced arthritis (CIA) and the possible mechanisms. Sixty rats were randomly divided into control and model: low-, medium-, and high-dose SZC and prednisone acetate (PA) groups, with 10 rats in each group. The CIA model was established in later 5 groups. The rats in low-, medium-, and high-dose SZC groups were intragastricallly administered with SZC, with dose of 0.5, 1, and 2 g/kg, respectively. The PA group was intragastricallly administered with 5 mg/kg PA. The treatment was performed for 3 weeks. Before treatment and after treatment, the paw swelling degree and polyarthritis index score of rats were measured. At the end of experiment, the serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) levels were determined. The expressions of Ras and Raf-1 protein in synovial tissue were detected. Results showed that, after treatment, compared with model group, in high-dose SZC and PA groups, the paw swelling degree, polyarthritis index score, serum TNF-α, IL-1β and NO levels, and synovial tissue Ras and Raf-1 protein levels were significantly decreased, respectively ( P &lt; 0.05). In conclusion, SZC has obvious protective effects on CIA in rats. The mechanisms may be related to its resistance of inflammatory reaction and down-regulation of Ras and Raf-l protein expressions in synovial tissue.

Modulation of Inflammatory Cytokines and Islet Morphology as Therapeutic Mechanisms of Basella alba in Streptozotocin-Induced Diabetic Rats

The mechanism of the previously reported antidiabetic effect of Basella alba is unknown. This study investigated the role of B. alba aqueous leaf extract in the modulation of inflammatory cytokines and islet morphology in streptozotocin-induced diabetic rats. Forty male Wistar rats, between 8 and 10 weeks old, were randomly divided into four groups (n = 10) and administered the following treatments: Healthy control (H-c) and Diabetic control (D-c) animals received normal saline 0.5 mL/100 g body weight daily, while Healthy Treatment (H-Ba) and Diabetic Treatment (D-Ba) rats received the plant extract 200 mg/kg body weight daily. All treatments were administered by oral gavage. Diabetes was induced in D-c and D-Ba rats by a single intraperitoneal injection of streptozotocin (55 mg/kg body). The body weight and fasting blood sugar (FBS) levels were recorded every week for 4 weeks, after which the rats were euthanized and samples collected for further analysis. After the experiment, FBS level was significantly reduced (p < 0.0001) in rats in the D-Ba group, but increased (p < 0.001) in rats in the D-c group. The absolute (H-c and H-Ba vs D-c, p < 0.05) and relative (D-Ba vs H-c, p < 0.05; D-Ba vs H-Ba, p < 0.005) weights of the pancreases were significantly higher after the experiment. The rats in the D-c group had significantly higher levels of serum interleukin-1β (p < 0.001 vs H-c; p < 0.05 vs H-Ba and D-Ba) and monocyte chemotactic protein-1 (p < 0.0001), but lower levels of interleukin-10 (p < 0.05) in comparison with the other groups. Histopathological examination revealed severe interstitial congestion, reduced islet area (p < 0.0001), and increased islet cell density in the D-c group compared with those in the D-Ba group. From these findings, it was concluded that the aqueous extract of B. alba stimulates the recovery of beta-islet morphology in streptozotocin-induced diabetic rats by modulating the peripheral production of inflammatory cytokines.