Content Of Inflammatory Mediators Research Articles

Qingjie Huagong decoction inhibits pancreatic acinar cell pyroptosis by regulating circHipk3/miR-193a-5p/NLRP3 pathway

BackgroundSafer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined. PurposeTo investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo. MethodsQJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro. A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot. Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3. ResultsOur results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway. ConclusionThis study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.

The role of leptin resistance in the development of thyroid neoplasia

Background. Leptin influences energy metabolism, as it is able to inform the central nervous system about adipose tissue reserves, and is also an important neuroendocrine regulator. Therefore, an increase in leptin stimulates thyrotropin-releasing hormone secretion, which leads to an increase of thyroid-stimula­ting hormone with normal or slightly elevated levels of thyroxine and triiodothyronine. Leptin imbalance leads to leptin resistance, which develops as a result of impaired sensitivity of hypothalamic receptors to leptin, its penetration through the blood-brain barrier, damage or dysfunction of these receptors, dysfunction of transport proteins accompanied by an increased content of inflammatory mediators that affect leptin receptors and, in turn, damage them. The purpose of the study was to reveal the relationship between hyperleptinemia and leptin resistance in people with different body weight and thyroid nodules. Materials and methods. One hundred and twenty-three patients were examined, who were divided into four groups depen­ding on the body mass index to determine the le­vels of leptin, insulin, and degree of insulin resistance: group 1 — excess body weight (n = 22); group 2 — class 1 obesity (n = 28); group 3 — class 2 obesity (n = 32); group 4 — class 3 obesity (n = 21). The control group consisted of persons with normal body weight (n = 20). Results. It was found that all examined patients had hyperleptinemia (34.5 ng/ml) simultaneously with hyperinsulinemia and insulin resistance (HOMA-IR was 8.3 units). Patients with thyroid neoplasia compared to individuals with normal body weight had significantly higher (by 1.3 times) serum leptin concentrations (p < 0.05; p < 0.001). The research proved that the level of leptine­mia is directly related to the body mass index, waist circumference (r = 0.54; p < 0.001) and hip circumference (r = 0.51; p < 0.001). Conclusions. Among patients with leptin resistance and insulin resistance against the background of obesity of various classes, thyroid neoplasms occur in 28 % of cases. Leptin resistance along with insulin resistance can be considered as independent risk factor for neoplasia. People with abdominal obesity need a mandatory exami­nation of the structural and functional state of the thyroid gland for early detection of nodular neoplasms.

N-Acetylcysteine Decreases Myocardial Content of Inflammatory Mediators Preventing the Development of Inflammation State and Oxidative Stress in Rats Subjected to a High-Fat Diet.

Arachidonic acid (AA) is a key precursor for proinflammatory and anti-inflammatory derivatives that regulate the inflammatory response. The modulation of AA metabolism is a target for searching a therapeutic agent with potent anti-inflammatory action in cardiovascular disorders. Therefore, our study aims to determine the potential preventive impact of N-acetylcysteine (NAC) supplementation on myocardial inflammation and the occurrence of oxidative stress in obesity induced by high-fat feeding. The experiment was conducted for eight weeks on male Wistar rats fed a standard chow or a high-fat diet (HFD) with intragastric NAC supplementation. The Gas-Liquid Chromatography (GLC) method was used to quantify the plasma and myocardial AA levels in the selected lipid fraction. The expression of proteins included in the inflammation pathway was measured by the Western blot technique. The concentrations of arachidonic acid derivatives, cytokines and chemokines, and oxidative stress parameters were determined by the ELISA, colorimetric, and multiplex immunoassay kits. We established that in the left ventricle tissue NAC reduced AA concentration, especially in the phospholipid fraction. NAC administration ameliorated the COX-2 and 5-LOX expression, leading to a decrease in the PGE2 and LTC4 contents, respectively, and augmented the 12/15-LOX expression, increasing the LXA4 content. In obese rats, NAC ameliorated NF-κB expression, inhibiting the secretion of proinflammatory cytokines. NAC also affected the antioxidant levels in HFD rats through an increase in GSH and CAT contents with a simultaneous decrease in the levels of 4-HNE and MDA. We concluded that NAC treatment weakens the NF-κB signaling pathway, limiting the development of myocardial low-grade inflammation, and increasing the antioxidant content that may protect against the development of oxidative stress in rats with obesity induced by an HFD.

Sichen Formula Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Blocking the TLR4 Signaling Pathways.

Sichen (SC) formula is a classic prescription of Tibetan medicine. Due to its potential anti-inflammatory effect, the SC formula has been clinically used to treat respiratory diseases for many years in the Chinese Tibet region. The present study aimed to investigate the anti-inflammatory effect of SC and explore the underlying mechanisms. SC formula was characterized by HPLC analysis. The acute lung injury (ALI) mouse model was induced by direct intratracheal lipopolysaccharide (LPS) instillation, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Meanwhile, RAW264.7 macrophages were stimulated by LPS. The contents of inflammatory mediators in the culture medium were determined by ELISA. Protein levels were determined by immunohistochemical staining or Western blotting. Nuclear localization of NF-κB, AP-1, and IRF3 was performed using immunofluorescence and Western blotting. In the LPS-induced ALI mouse model, SC treatment suppressed the secretion of inflammatory mediators (TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and RANTES) in BALF. SC treatment hindered the recruitment of macrophages. SC treatment also inhibited the expression of CD68, p-p65, and TLR4 in the lung tissue. In the LPS-exposed RAW264.7 cells, the cell viability was not changed up to 400 μg/mL of SC. SC concentration-dependently suppressed the production of nitric oxide, prostaglandin E2, TNF-α, IL-6, MCP-1, MIP-1α, and RANTES in LPS-challenged RAW264.7 cells. The expression levels of iNOS, COX-2, p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/β, p-IκB, p-p65, p-c-Jun, and p-IRF3 were decreased after SC treatment. Moreover, the nuclear translocation of p65, c-Jun, and IRF3 was also blocked by SC treatment. SC treatment inhibited the inflammatory responses in LPS-induced ALI mouse model/RAW264.7 macrophages. The underlying mechanism of this action may be closely associated with the suppression of TLR4 signaling pathways. These research findings provide further pharmacological justifications for the medicinal use of SC in the management of respiratory diseases.

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet.

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of AktSer473 and AMPKThr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.

Effects of Warm Acupuncture Combined with Meloxicam and Comprehensive Nursing on Pain Improvement and Joint Function in Patients with Knee Osteoarthritis.

Objective To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis. Method Eighty-one patients with KOA were randomly divided into control group (CG), traditional Chinese medicine group (TCMG), and combined group (JG). The CG was treated with meloxicam. The TCMG received warm acupuncture treatment. The JG was treated with meloxicam combined with warm acupuncture. Three groups were given comprehensive nursing intervention, and the course of treatment was 4 weeks. Knee function was assessed by knee pain, activity, stability, walking ability, and ability to walk up and down stairs. Improvement time of clinical symptoms of patients was assessed from knee pain, swelling, and movement limitation. Pain mediators (prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT)) were detected by enzyme-linked immunosorbent assay (ELISA). Oxidative stress indicators (superoxide dismutase (SOD) and malondialdehyde (MDA)) of the enrolled patients were detected by water-soluble tetrazolium-1 (WST-1) and the thiobarbituric acid (TBA) method. The clinical efficacy was assessed by the visual analog scale (VAS) score. Results After treatment, the pain scores of the three groups decreased, and the scores of mobility, stability, walking ability, and the ability to walk up and down stairs increased. Compared with the CG and the TCMG, the JG had a greater range of changes in pain, mobility, stability, walking ability, and ability to walk up and down stairs after treatment. After 7 d, 14 d, and 28 d treatment, PGE2, SP, DA, 5-HT, and MDA in the three groups were decreased compared with before treatment, and the decrease in the JG was more obvious than that in the CG and the TCMG. SOD levels in the three groups were increased, and the increase in the JG was more obvious than that in the CG and the TCMG. The total effective rate of the JG (96.30%) was significantly different from that of the CG (77.78%) and the TCMG (81.48%). The improvement time of knee pain, swelling, and movement limitation in the JG was shorter than that in the CG and the TCMG, and the difference in the improvement time of movement limitation in the TCMG was statistically significant. Conclusion Warm acupuncture combined with meloxicam and comprehensive nursing can effectively improve knee swelling and pain in patients with KOA, and the mechanism may be related to reducing the content of inflammatory mediators.

The analgesic activities of total alkaloids of the ethnic medicine Cynanchum komarovii Al. Iljinski

Ethnopharmacological relevanceCynanchum komarovii Al. Iljinski is a ethnomedicinal herb and this ethno-medicine is used mainly to treat arthritis, toothache, reducing phlegm, relieving cough. Total alkaloids of Cynanchum komarovii Al. Iljinski (TACKI) is the main active compound of Cynanchum komarovii Al. Iljinski. Previous investigations have revealed that TACKI can significantly inhibit rat foot swelling caused by carrageenan; it has a significant inhibitory effect on granulation tissue proliferation. Pharmacology study showed that Cynanchum komarovii Al. Iljinski has analgesia, anti-inflammatory, antibacterial, anti-tumor, relieving cough and relieving asthma. However, there is no any investigation on the mechanism of analgesia and anti-inflammation. Aim of the studyTo clarify the analgesic effect and material basis of Cynanchum komarovii Al. Iljinski, determine the analgesic effect of TACKI, and provide experimental data support for its traditional application in the treatment of various pains. Materials and methodsTACKI were prepared by the traditional acid extraction and alkaline precipitation method, and TACKI was analyzed through classic animal models of acute antinociceptive animal models and chronic antinociceptive. Evaluation of analgesic effects, and preliminary discussion of the mechanism of its analgesic effects were performed in this work. ResultsAcute toxicity experiments showed that the LD50 of TACKI mice was 2960.88 mg/kg, and symptoms of poisoning appeared. Patholog of liver and kidney studies have shown that TACKI reduces eosinophils and increases basophils in kidney glomeruli. In the study of analgesic effects, TACKI had analgesic activity through the PWL, formalin test, and acetic acid writhing test. In the chronic inflammatory antinociceptive study, the latency of the withdrawal reflex in the TACKI group was prolonged, and the mechanical withdrawal reflex threshold was significantly increased. The protein expression of NMDA, GFAP and Iba-1 in rat brain tissue can be reduced significantly byTACKI. Meanwhile, the content of TNF-α and IL-6 in rat brain tissue is reduced. ConclusionTACKI has a significant analgesic activities. It may be related to inhibiting the activation of astrocytes and reducing the content of inflammatory mediators.

Bioactive constituents of Mosla chinensis-cv. Jiangxiangru ameliorate inflammation through MAPK signaling pathways and modify intestinal microbiota in DSS-induced colitis mice

BackgroundMosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency. PurposeThis study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms. MethodsThe bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored. ResultsTotally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE2) and cytokines (TNF-α, IL-6, IL-1β). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model. ConclusionsThis study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.

Network pharmacology and in vitro study of Fengreqing oral liquid in the intervention of wind-heat pattern.

To investigate the underlying mechanism of the effect of Fengreqing oral liquid (, FOL) on wind-heat pattern (WHP). In this study, we predicted the potential targets of FOL via the approach of network pharmacology and verified it by in vitro inflammation model. In the network pharmacology part, two strategies, namely the direct target search and the indirect one, were used to collect the target sets of FOL in WHP treatment. The enrichment analysis was carried out by David database and ClueGo plug-in in Cytoscape. Furthermore, the potential targets were mapped in the candidate pathways. In the verification experiment section, in vitro model of lipopolysaccharide (LPS) induced RAW 264.7 was used to confirm the predictive results in the network pharmacology part. Through the two screening strategies, a total of 141 non-repetitive intervention targets of FOL on WHP were obtained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the intervention effect was mainly focused on the anti-inflammatory effect, and the Toll-like receptor signaling pathway was one of the most critical regulatory pathways. Further mapping analysis showed that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling transfer might be the key part of regulating the concentration of inflammation mediators of FOL in the Toll-like receptor signaling pathway. In vitro experiment showed that FOL significantly reduced the levels of NO, IL-1, IL-6, and TNF-α produced by RAW264.7 induced by LPS. Further immunofluorescence found that this effect is related to the regulation of PI3K-AKT pathway activity by FOL. FOL can intervene in WHP by regulating the content of inflammatory mediators via the PI3K-AKT pathway.

L-carnitine and Co Q10 ameliorate potassium dichromate -induced acute brain injury in rats targeting AMPK/AKT/NF-κβ

Adenosine monophosphate-activated protein kinase (AMPK) has a crucial role in neuroprotection. It phosphorylates serine/threonine kinase (Akt) Substrate inhibiting the inflammatory responses induced by the nuclear factor-κB (NF-κB). Exposure to chromium VI dust among workers has been reported and induced brain injury, as the absorption of chromium through the nasal membrane has been found to deliver it directly to the brain. The study aimed to investigate the influence of administration of L-carnitine or/and Co Q10 as theraputic agents against potassium dichromate (PD)-induced brain injury via AMPK/AKT/NF-κβ signaling pathway. Brain injury was induced by PD intranasally as a single dose of 2 mg/kg, 24 h latter rats received L-carnitine (100 mg/kg; orally), Co Q10 (50 mg/kg; orally) and L-carnitine (50 mg/kg; orally) + Co Q10 (25 mg/kg; orally) respectively for 3 days. Locomotor activity was assessed before and at the end of the experiment, then, biochemical and histopathological investigations were assessed in brain homogenate. The exposure of rats to PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in GSH brain contents with an increase in brain contents of TNF-α, IL-6, and NF-kβ and reduced AMPK and AKT brain contents as compared to the control group. Treatment with L-carnitine + Co Q10 ameliorated cognitive impairment and oxidative stress, decreased the brain contents of inflammatory mediators; TNF-α, IL-6, and NF-κβ elevated AMPK and AKT, as compared to each drug. Also, L-carnitine + Co Q10 administration restored morphological changes as degenerated neurons and necrosis. L-carnitine + Co Q10 play important role in AMPK/AKT/NF-κβ pathway that responsible for their antioxidant and anti-inflammatory effects against PD-induced brain injury in rats.

Characterization of Molecular Species and Anti-Inflammatory Activity of Purified Phospholipids from Antarctic Krill Oil.

The phospholipids (PLs) from Antarctic krill oil were purified (>97.2%) using adsorption column chromatography. Forty-nine PL molecular species were characterized by ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Most of molecular species contained eicosapentaenoic acid (EPA, 20:5), docosahexaenoic acid (DHA, 22:6), docosapentaenoic acid (DPA, 22:5), and arachidonic acid (AA, 20:4). Notably, a special species PC (20:5/22:6) (1298.17 nmol/g) and many ether PLs were detected. The Antarctic krill PL liposome (IC50 = 0.108 mg/mL) showed better anti-inflammatory activity than crude Antarctic krill oil (IC50 = 0.446 mg/mL). It could block NF-κB signaling pathway via suppression of IκB-α degradation and p65 activation and dose-dependently reduce the cellular content of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In addition, it can suppress carrageenan-induced mouse paw swelling. Results from the present study could provide a reference for better evaluation of nutritional and medicinal values of Antarctic krill oil.

Research Note: Anti-inflammatory effects and antiviral activities of baicalein and chlorogenic acid against infectious bursal disease virus in embryonic eggs

The purpose of this study was to investigate if baicalein and chlorogenic acid could inhibit the inflammatory responses induced by and protect against infectious bursal disease virus (IBDV) in chicken embryonic eggs. Nine-day-old embryonated chicken eggs were randomly divided into 3 groups of 50 eggs per group: 1) treatment with varying concentrations of baicalein, 2) treatment with varying concentrations of chlorogenic acid, or 3) left untreated as a control. Forty-eight hours after hatching, each group was inoculated with a very virulent IBDV isolate, and the survival of the embryo was monitored daily until the embryonic livers were collected 72 h after inoculation. After IBDV infection, the viral loads in the embryonic livers were evaluated using qRT-PCR, and the hepatic content of inflammatory mediators, such as histamine, interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), and nuclear factor-kappa B (NF-κB), were examined. Significant antiviral potential was demonstrated at concentrations of 108 and 215 μg/egg of baicalein and chlorogenic acid, respectively. We observed a concentration-dependent response in the antiviral properties of these chemicals. Treating the embryos with baicalein and chlorogenic acid significantly reduced histamine production. Moreover, pretreatment with baicalein and chlorogenic acid significantly inhibited NF-κB activation, and this inhibited the subsequent production of the proinflammatory cytokines TNF-α and IL-1β in the context of IBDV infection. These findings suggest that baicalein and chlorogenic acid have anti-IBDV properties, and they may be useful in the prevention of inflammation-related diseases.

Research on feasibility of in vitro inflammatory wound microenvironment simulated by using inflammatory wound tissue homogenate of mice

Research on feasibility of in vitro inflammatory wound microenvironment simulated by using inflammatory wound tissue homogenate of mice

Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes

Ginsenoside Rg1 is an active ingredient extracted from the roots of ginsenoside, and an α-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis was used to investigate the protective effect of Rg1 on cholestasis. 48 SD male rats were randomly divided into 6 groups: control group, model group, UDCA group (ursodeoxycholic acid), low-dose Rg1 group (10 mg/kg), medium-dose Rg1 group (20 mg/kg) and high-dose Rg1 group (40 mg/kg). The model group, the UDCA group and all the Rg1 group were then intragastrically administered with 80 mg/kg ANIT, and the control group were given equal volume of olive oil. Then the pathological changes in liver tissue were observed, the secretion of bile in the bile duct was measured, and the biochemical markers in serum were quantified, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transfer peptidase (GTP) and the content of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA). The contents of inflammatory mediators in serum were quantified, including tumor necrosis factor (TNF-α), γ-interferon (IFN-γ) and interleukin-1β (IL-1β). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver homogenate were quantified. Expression of farnesoid X receptor (FXR), transporters and metabolic enzymes in liver tissue was monitored. Rg1 treatment improved liver tissue pathological damage, promoted bile secretion and significantly reduced serum levels of the intrahepatic cholestasis markers ALT, AST, ALP, GTP, TBIL, DBIL and TBA. Rg1 increased the activity of SOD and GSH-Px in liver homogenate, while, reducing the serum levels of MDA and inflammatory mediators. Rg1 also regulated the expression of FXR, bile acid transporters and metabolic enzymes. Overall, Rg1 alleviated liver injury by improving secretion of bile and normalizing the activity of enzymes in the serum. The protective mechanism appeared to be related to the activation of FXR and regulation of liver transporters and metabolic enzymes.

Pidotimod in the treatment of pediatric recurrent respiratory tract infection.

Objective:To observe the clinical efficacy of pidotimod in the treatment of recurrent respiratory tract infection in children.Methods:One hundred thirty-two patients with recurrent respiratory tract infection who received treatment in Tianan City Central Hospital were selected and divided into an observation group and a control group using random number table, 66 in each group. Patients in the control group were given conventional treatment, while patients in the observation group were given conventional treatment and pidotimod treatment; the clinical efficacy of the two therapies was compared. The levels of IgG and IgM were measured after treatment.Results:The vital signs and the content of inflammatory mediator and Th1/Th2 in serum before and after treatment were compared, and the clinical efficacy of the two groups was evaluated. The fever, pulmonary rale, cough and antiadoncus of patients in the observation group disappeared earlier than those in the control group (P<0.05). The onset duration of respiratory tract infection and days of antibiotic application of the observation group were shorter than those of the control group after treatment (P<0.05). The times of infection of the observation group were less than that of the control group (P<0.05). Before treatment, the two groups had no significant difference in the content of inflammatory mediators and Th1/Th2 in the serum (P>0.05). The serum content of tumor necrosis factor (TNF)-α and interleukin (IL)-4 of the two groups one week after treatment was lower than that before treatment, and the content of interferon (IFN)-γ and IFN-γ/IL-4 were higher than that before treatment; moreover the observation group had lower serum content of TFN-α and IL-4 and lower content of IFN-γ and IFN-γ/IL-4 compared to the control group (P<0.05). The overall response rate of the observation group was 92.4%, much higher than 81.8% in the control group (P<0.05).Conclusion:Pidotimod has a remarkable efficacy in the treatment of pediatric recurrent respiratory tract infection because it can effectively inhibit the infection and optimize Th1/Th2 immune function.

Salvianolic Acid B and Ginsenoside Re Synergistically Protect Against Ox-LDL-Induced Endothelial Apoptosis Through the Antioxidative and Antiinflammatory Mechanisms.

Salvianolic acid B (SalB) and ginsenoside Re (Re) protect endotheliocytes against apoptosis through different mechanisms. However, whether both compounds could synergistically protect endothelial cells against oxidized low-density lipoprotein (Ox-LDL)-induced apoptosis is unclear. This study aimed to assess the protective effect of combined SalB and Re (SR) treatment on Ox-LDL-induced endothelial apoptosis and to explore the mechanism underlying this effect. Results showed that SalB, Re, or SR could protect against Ox-LDL-induced endothelial apoptosis. Furthermore, the composition of SR was optimized through central composite design with response surface methodology. SR with a composition of 60 μg/mL of SalB and 120 μg/mL of Re exerted the optimal protective effect. Network pharmacology research revealed that SalB and Re in SR synergistically protect against Ox-LDL-induced endothelial apoptosis by regulating oxidative stress and phlogistic pathways. In vitro experiments confirmed these results. Compared with the same dose of SalB or Re alone, SR significantly decreased the contents of inflammatory mediators and increased the activities of antioxidant enzymes. SR could synergistically restore the balanced redox state of the cells and inhibit the activation of nuclear transcription factor kappa B and the caspase cascade by activating the phosphatidylinositol 3 kinase/protein kinase B pathway and inhibiting the phosphorylation of p38 mitogen-activated protein kinase. These pathways are regulated by down-regulating the expression of lectin-like Ox-LDL receptor-1 and NADPH oxidase and up-regulating the expression of estrogen receptor alpha. Therefore, SR effectively prevents Ox-LDL-induced endothelial apoptosis through antioxidative and antiinflammatory mechanisms.

Sodium butyrate enhances intestinal integrity, inhibits mast cell activation, inflammatory mediator production and JNK signaling pathway in weaned pigs.

The present study aimed to investigate the effects of sodium butyrate on the intestinal barrier and mast cell activation, as well as inflammatory mediator production, and determine whether mitogen-activated protein kinase signaling pathways are involved in these processes. A total of 72 piglets, weaned at 28 ± 1 d age, were allotted to two dietary treatments (control vs. 450 mg/kg sodium butyrate) for 2 wk. The results showed that supplemental sodium butyrate increased daily gain, improved intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function reflected by increased transepithelial electrical resistance and decreased paracellular flux of dextran (4 kDa). Moreover, sodium butyrate reduced the percentage of degranulated mast cells and its inflammatory mediator content (histamine, tryptase, TNF-α and IL-6) in the jejunum mucosa. Sodium butyrate also decreased the expression of mast cell-specific tryptase, TNF-α and IL-6 mRNA. Sodium butyrate significantly decreased the phosphorylated ratio of JNK whereas not affecting the phosphorylated ratios of ERK and p38. The results indicated that the protective effects of sodium butyrate on intestinal integrity were closely related to inhibition of mast cell activation and inflammatory mediator production, and that the JNK signaling pathway was likely involved in this process.

Cytokine status’ pattern in acute period of ischemic stroke subtypes

Purpose The aim of this study was to assess a different pattern of inflammatory mediators in relation of ischemic stroke subtypes in acute period. Materials and Methods. The study involved 482 patients with different ischemic stroke (IS) subtypes. We studied the content of inflammatory interleukins (IL-1β, IL-2, IL-6, IL-8, CRP, TNF-α) and anti-inflammatory interleukin IL-10 in blood serum. Results The study revealed increasing content of pro-inflammatory cytokines in acute period of IS subtypes, especially at Large Artery AtheroSclerosis (LAAS) and CardioEmbolic Infarct (CEI). In patients with LAAS the level of IL-2, IL-6 and CRP was significantly higher compared to other IS subtypes. The content of IL-10 was significantly lower compared to patients with Undetermined Etiology (UDE) stroke and LACunar (LAC) stroke. We established the relationship between the concentration of IL-1β and IL-6 with the severity of LAAS, CEI and UDE on the 1 st day of stroke. On the 7 th day the concentration of IL-1β and IL-8 was significantly decreased at LAC, IL-2 – at LAC and LAAS, IL-6 and TNF-α at LAC and UDE. At LAAS the content of inflammatory mediators depended on the degree of arteries stenosis, the presence of unstable atherosclerotic plaques, the intima-media thickness. We found a direct relationship between the severity of LAAS and CEI on the 14 th day with the CRP concentration on the 1 st day (at LAAS – (r = 0.73, p = 0.003), at CEI – (r = 0.71, p = 0.002), indicating predictive value of CRP-content on the course of acute period of IS subtypes. We established the dependence between cardiac morphometric parameters with the level of pro-inflammatory interleukins in acute period of UDE. We found the relation between the content of IL-1β, IL-6 with left ventricular myocardial mass index at UDE. Conclusions The content of inflammatory mediators in acute period of ischemic stroke depends on the pathogenic subtype of stroke.

A clinical study of multiple trauma combined with acute lung injury

ObjectiveTo study the changes of the contents of inflammatory mediators in serum of polytrauma patients with acute lung injury (ALI) and their correlation with the disease. MethodsPatients suffering from multiple trauma combined with ALI were selected as ALI group (n = 54). Patients suffering from multiple trauma without ALI were considered as the control group (n = 117). The severity of the disease of patients in the two groups was assessed. Arterial blood was extracted for blood gas analysis. Venous blood was extracted to detect the contents of inflammatory mediators tumor necrosis factor-α, interleukin-1β (IL-1β), IL-10, granulocyte-macrophage colony stimulating factor, NO, endothelin-1. ResultsThe scores of injury severity score [(25.42 ± 3.58) vs. (17.03 ± 2.25)], systemic inflammatory response syndrome [(3.85 ± 0.52) vs. (2.20 ± 0.36)] and acute physiology and chronic health evaluation II [(92.63 ± 11.04) vs. (60.46 ± 8.87)] in patients in ALI group were all significantly higher than those in the control group and its correcting shock time [(8.39 ± 1.05) vs. (5.15 ± 0.72) h] was longer than that of the control group. The amount of blood transfusion [(674.69 ± 93.52) vs. (402.55 ± 57.65) mL] was greater than that in the control group. The contents of the arterial partial pressure of oxygen [(76.65 ± 9.68) vs. (86.51 ± 10.56) mmHg], arterial blood pressure of carbon dioxide [(27.76 ± 4.82) vs. (36.78 ± 5.82) mmHg] and arterial partial pressure of oxygen/fraction of inspired oxygen [(236.94 ± 36.49) vs. (353.95 ± 47.76)] were all significantly lower than those in the control group. The contents of serum tumor necrosis factor-α, IL-1β, IL-10, granulocyte-macrophage colony stimulating factor, NO and endothelin-1 were obviously higher than those of control group and also positively correlated with the scores of injury severity score, systemic inflammatory response syndrome and acute physiology and chronic health evaluation II. ConclusionsThe activation of the inflammatory reactions and the excessive release of inflammatory mediators are the key link causing multiple trauma combined with ALI. The content of serum inflammatory mediators is closely related to the severity of the disease.

Therapeutic experience of the application of anisodamine on acute lung injury

ObjectiveTo investigate the effect of anisodamine combining with conventional therapy on the degree of lung injury and inflammatory reaction of patients with acute pulmonary contusion. MethodsA total of 48 patients with acute pulmonary contusion treated in our hospital emergency department from April 2011 to October 2015 were enrolled as the research object and were divided into experimental group and control group by using a method of random number table. Experimental group received anisodamine combining with conventional therapy and control group received conventional therapy. In the process of the treatment, the mechanical ventilation time, hospital stays in intensive care unit and the number of cases developed into acute respiratory distress syndrome and multiple organ dysfunction syndromes of patients in two groups were observed. Oxygenation indexes of patients were respectively calculated on Days 1, 2 and 3 after treatment. The contents of inflammatory mediators in serum were detected on Day 3 after treatment. ResultsThe mechanical ventilation time and hospital stays in intensive care unit [(9.52 ± 1.41) vs. (14.57 ± 2.51) days] of patients in experimental group were significantly shorter than those in control group, and the number of cases developed into acute respiratory distress syndrome [1 (4.17%) vs. 9 (37.50%)] and multiple organ dysfunction syndrome [1 (4.17%) vs. 7 (29.17%)] was significantly less than those in control group. Oxygenation indexes (294.52 ± 41.26 vs. 257.63 ± 38.52; 357.74 ± 47.74 vs. 279.87 ± 31.46; 396.71 ± 55.12 vs. 279.87 ± 31.46) of patients were respectively calculated on Days 1, 2 and 3 after treatment, which were significantly higher than those in the control group. On Day 3 after treatment, the contents of serum C-reactive protein [(7.94 ± 1.05) vs. (14.49 ± 2.97) mg/L], tumor necrosis factor α [(264.69 ± 41.58) vs. (417.87 ± 64.51) ng/L], interleukin-6 (IL-6) [(147.72 ± 21.36) vs. (257.68 ± 41.54) ng/L], IL-8 [(93.68 ± 12.52) vs. (145.62 ± 22.65) ng/L], IL-10 [(205.64 ± 31.56) vs. (336.62 ± 51.38) ng/L] and myeloid cells-1 (73.32 ± 10.39 vs. 114.45 ± 18.51) of patients in experimental group were significantly lower than those in the control group. ConclusionsThe anisodamine combining with conventional therapy can relieve the degree of lung injury caused by acute pulmonary contusion, improve ventilatory function, lower the incidence of acute respiratory distress syndrome and multiple organ dysfunction syndrome and inhibit the activation of inflammatory reaction and the release of inflammatory mediators.