Regulation Of Inflammatory Reactions Research Articles

Signaling by Neutrophil G Protein-Coupled Receptors that Regulate the Release of Superoxide Anions.

In human peripheral blood, the neutrophil granulocytes (neutrophils) are the most-abundant white blood cells. These professional phagocytes are rapidly recruited from the bloodstream to inflamed tissues by chemotactic factors that signal danger. Neutrophils, which express many receptors that are members of the large family of G protein-coupled receptors (GPCRs), are critical for the elimination of pathogens and inflammatory insults, as well as for the resolution of inflammation leading to tissue repair. Danger-signaling molecular patterns such as the N-formylated peptides that are formed during bacterial and mitochondrial protein synthesis and recognized by formyl peptide receptors (FPRs) and free fatty acids recognized by free fatty acid receptors (FFARs) regulate neutrophil functions. Short peptides and short chain fatty acids activate FPR1 and FFA2R, respectively, while longer peptides and fatty acids activate FPR2 and GPR84, respectively. The activation profiles of these receptors include the release of reactive oxygen species (ROS) generated by the NADPH oxidase. Activation of the oxidase and the production of ROS are processes that are regulated by proinflammatory mediators, including TNFα and GM-CSF. The receptors have signaling and functional similarities, although there are also important differences, not only between the two closely related neutrophil FPRs, but also between the FPRs and the FFARs. In neutrophils, these receptors never walk alone, and additional mechanistic insights into the regulation of the GPCRs and the novel regulatory mechanisms underlying the activation of NADPH oxidase advance our understanding of the role of receptor transactivation in the regulation of inflammatory reactions.

Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BackgroundThe monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown.MethodsElectrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test.ResultsHuman eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining.ConclusionsOur findings suggest eMSC improves regeneration of injured endometrium in mice.

69 Activation of the Aryl Hydrocarbon Receptor - a Major mode of Combustion Particle Toxicity?

Abstract Combustion-derived particles constitute an important part of the fine fraction of particulate matter with aerodynamic diameter less than 2.5 microns (PM2.5) and are considered central for the adverse effects of air pollution. Understanding the mechanisms of combustion particle toxicity may shed light on the components and characteristics of outdoor air PM driving adverse health effects. This may also enable more targeted and efficient policies to improve air quality and promote health and wellbeing. The aryl hydrocarbon receptor (AhR) is a ligand dependent transcription factor, originally discovered for its ability to bind polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds and regulate PAH metabolism. It is now clear that AhR regulates a variety of biological and toxicological responses, overlapping to a considerable degree with the effects of combustion PM and ambient PM2.5. Studies from our lab and others also suggest that AhR activation is among the most sensitive responses to combustion PM exposure, induced at orders of magnitude lower concentrations than many other endpoints. This talk will discuss the potential role of the AhR and PAHs in combustion PM toxicity based on previous and ongoing work, with a main focus on intracellular signalling and regulation of inflammatory reactions in lung epithelial cells and vascular endothelial cells.

Propofol Affects H/R Induced Alveolar Macrophage Death via TLR4/NF-κB/NLRP3 Signaling Pathway

Acute lung injury (ALI) is one of the most common acute and critical diseases in clinic. The main pathological features of ALI are increase of pulmonary Vascular permeability, accumulation of inflammatory cells and pulmonary dysfunction due to diffuse pulmonary edema. At present, it is generally believed that the main pathogenesis of ALI is the uncontrolled inflammatory response in the lung. It has been found that cell death plays an important role in the regulation of inflammatory reaction in acute lung injury. Propofol, a new fast-acting, short-acting intravenous anesthetic, it is known that ALI can be alleviated by inhibiting the release of inflammatory factors and inhibiting the anoxia/reoxygenation-induced autophagy, chemotaxis and oxidative stress in macrophages, however, the mechanism of its role in the death of alveolar macrophage remains unknown. Therefore, the aim of this study was to investigate the role of propofol in alveolar macrophage death and its mechanism through anoxia-reoxygenation induced ALI. NR8383 was alveolar macrophage as anoxia-reoxygenation model. LDH release, CCK-8, Elisa and Western Blot were used to investigate the pathway of propofol through TLR4/NF-κB/NLRP3 signaling pathway, mechanism of inhibition of hypoxia-reoxygenation induced alveolar macrophage death of NR8383. The results showed that propofol decreased the release of LDH and the content of IL-1β and IL-18. In addition, propofol pretreatment reduced the protein expression levels of TLR4 downstream pathways (p65 phosphorylation, NLRP3, cleaved-caspase-1, and GSDMD-N), all of which could be reversed by TLR4 receptor antagonist and NLRP3 receptor inhibitors, it’s causing a decrease in alveolar macrophage activity. The results showed that propofol could significantly reduce anoxia-reoxygenation-induced alveolar macrophage death. Propofol may modulate alveolar macrophage death through TLR4/NF-κB/NLRP3 inflammatory signaling pathway, thereby alleviating anoxia-reoxygenation induced Ali, suggesting that propofol may be a potential drug for the treatment of Ali.

Uncovering the effective substances and mechanism of Ipomoea pes-caprae against rheumatoid arthritis using liquid chromatography-mass spectrometry and targeted network pharmacology.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and anti-rheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.

Analysis of Differential TLR Activation in a Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative and autoimmune disease affecting the central nervous system (CNS). The precise etiology of MS is still undeciphered, and signs and symptoms of the disease are varied and complex, ranging from axonal degeneration, synaptic, and neuronal loss to demyelination. Inflammation plays a critical role in determining the onset and the progression of MS, but there is still a lot of information missing before scientists come to understand what are the factors that contribute to the establishment of the neuroinflammation. Thus, various murine models, each representative of a specific hallmark of MS, are used to study the processes underlying the pathogenetic mechanisms of the disease in an attempt to find effective drugs for its treatment. Among the many causes of MS, viral infections appear to be one of the most prominent ones. In this scenario, the comprehension of the role of receptors activated upon the recognition of viral, and in general microbial, components in determining onset and progression of the neuroinflammation is of paramount importance. Toll-like receptors (TLRs) are evolutionarily conserved receptors that recognize several pathogen-associated molecular patterns (PAMPs), common structures of the pathogens, or the damage caused by the pathogens within the host. TLRs are thus directly involved in the regulation of inflammatory reactions and in the activation of the innate and, subsequently, the adaptive immune responses crucial for the elimination of infectious pathogens. The role of TLR activation in the development of MS is widely studied in various murine models of MS, as well as in MS patients. In this chapter, we will summarize the current knowledge about the contribution of TLRs to the development or progression of MS, and we will illustrate different methods commonly used for the investigation of the role of different TLRs in various murine models of the disease.

Based on UPLC/MS/MS and Bioinformatics Analysis to Explore the Difference Substances and Mechanism of Curcumae Radix (Curcuma wenyujin) in Dysmenorrhea.

Curcumae Radix (CW) is traditionally used to treat dysmenorrhea caused by uterine spasm. However, the changes of its composition and anti-uterine spasms during vinegar processing and the mechanism in treating dysmenorrhea are not clear. To elucidate the changes of anti-uterine spasm and its substance basis, and the mechanism of treating dysmenorrhea before and after vinegar processing. The uterine spasm contraction model was established, and the uterine activity and its inhibition rate were calculated to evaluate the differences. The main chemical constituents of CW were quickly analyzed by UPLC-Q-TOF-MS/MS technology, and the differences between them were explored by multivariate statistical analysis. Then, the regulatory network of "active ingredients-core targets-signal pathways" related to dysmenorrhea was constructed by using network pharmacology, and the combination between differential active components and targets was verified by molecular docking. CW extract relaxed the isolated uterine by reducing the contractile tension, amplitude, and frequency. Compared with CW, the inhibitory effect of vinegar products was stronger, and the inhibition rate was 70.08 %. 39 compounds were identified from CW and 13 differential components were screened out (p<0.05). Network pharmacology screened 11 active components and 32 potential targets, involving 10 key pathways related to dysmenorrhea. The results of molecular docking showed that these differentially active components had good binding activity to target. It was preliminarily revealed that CW could treat dysmenorrhea mainly through the regulation of inflammatory reaction, relaxing smooth muscle and endocrine by curcumenone, 13-hydroxygermacrone, (+)-cuparene, caryophyllene oxide, zederone, and isocurcumenol.

Effect of EGCG on inflammatory reaction in rats suffered cerebral ischemia/reperfusion injury.

Epigallocatechin gallate (EGCG) is the main bioactive component of polyphenols in tea, which has a variety of biological effects. The neurologic injury caused by cerebral ischemia/reperfusion (I/R) is closely related to the inflammatory reaction. The pro-inflammatory factor interleukin-1β (IL-1β) and the anti-inflammatory factor interleukin-10 (IL-10) play important roles in the regulation of inflammatory reaction. This study aims to explore the effect of EGCG on water content, myeloperoxidase (MPO) activity, IL-1β and IL-10 in brain tissues of rats suffered cerebral I/R injury. Middle cerebral artery occlusion model of SD rats was established by suture embolic method. After ischemia for 1.5 h, the nylon thread was pulled out and reperfusion was performed for 24.0 h. SD rats were randomly divided into 5 groups: a sham group, an I/R group, a EGCG1 group (I/R+12.5 mg/kg EGCG), a EGCG2 (I/R+25.0 mg/kg EGCG), and a EGCG3 group (I/R+50.0 mg/kg EGCG). The sham group was the same as the I/R group except that the middle cerebral artery was not blocked. The water content in brain tissues of rats was measured by dry and wet weight method, and MPO activity was detected by colorimetry. The levels of IL-1β and IL-10 mRNA were determined by RT-PCR, and the contents of IL-1β and IL-10 were determined by ELISA. In addition, primary cultured cortical neurons of SD rats were randomly divided into 3 groups: a control group, an oxygen-glucose deprivation/reperfusion (OGD/R) group, and an OGD/R+EGCG group (OGD/R+50.0 μmol/L EGCG). The effects of EGCG on the levels of IL-1β and IL-10 protein in neurons were assessed by Western blotting. Compared with the sham group, water content, MPO activity, the contents of IL-1β and IL-10 were significantly increased (P<0.05 or P<0.01), the mRNA expression of IL-1β and IL-10 were obviously up-regulated (both P<0.01) in cerebral tissues of rats in the I/R group. Compared with the I/R group, water content and MPO activity in cerebral tissues of rats were significantly decreased (both P<0.01), the content of IL-1β (P<0.01) were significantly decreased and IL-10 (P<0.01) were significantly increased in the EGCG3 group. Compared with the I/R group, the mRNA expression of IL-1β was obviously down-regulated and the mRNA expression of IL-10 was obviously up-regulated in the EGCG2 and the EGCG3 group (P<0.05 or P<0.01). Compared with the control group, the protein levels of IL-1β and IL-10 in neurons were significantly increased in the OGD/R group (both P<0.01). Compared with the OGD/R group, the protein expression of IL-1β was obviously down-regulated and the protein expression of IL-10 was obviously up-regulated in neurons in the OGD/R+EGCG group (both P<0.01). EGCG can inhibit the inflammatory reaction induced by cerebral I/R, which may be related to down-regulating the expression of pro-inflammatory factor IL-1β and up-regulating anti-inflammatory factor IL-10.

Advances in olfactory ensheathing cells for the treatment of spinal cord injury

Spinal cord injury is a highly disabled neurological disease, and there is still a lack of effective treatments. Studies have proved that olfactory ensheathing cells are one of the ideal seed cells for promoting nerve regeneration after spinal cord injury. Olfactory ensheathing cells can promote axonal germination and elongation through secretion, interaction with astrocytes, regulation of inflammatory reaction, migration characteristics, myelination, anti-oxidation, lipid regulation and other channels. Thus olfactory ensheathing cells play the role of neuroprotection and nerve repair. In recent years, some studies have used bioengineering, tissue engineering, reprogramming and other technologies to enhance the efficacy of olfactoryensheathing cells from different aspects, thereby providing new therapeutic strategies for optimizing the cell therapy of spinal cord injury. This article will summarize the mechanism of olfactory ensheathing cells in repairing spinal cord injury, and review the progress of optimizing strategy of olfactory ensheathing cells in treating spinal cord injury recently, so as to provide new research ideas for the further developing the repair potential of olfactory ensheathing cells and optimize the cell therapy effect of spinal cord injury.

Regulation of Inflammatory Reaction in Health and Disease.

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.

Small molecules targeting cyclooxygenase/prostanoid cascade in experimental brain ischemia: Do they translate?

Acute brain ischemia accounts for most of stroke cases and constitutes a leading cause of deaths among adults and permanent disabilities in survivors. Currently, the intravenous thrombolysis is the only available medication for ischemic stroke; mechanical thrombectomy is an emerging alternative treatment for occlusion of large arteries and has shown some promise in selected subsets of patients. However, the overall narrow treatment window and potential risks largely limit the patient eligibility. New druggable targets are needed to innovate the treatment of brain ischemia. As the rate-limiting enzyme in the biosyntheses of prostanoids, cyclooxygenase (COX), particularly the inducible isoform COX-2, has long been implicated in mechanisms of acute stroke-induced brain injury and inflammation. However, the notion of therapeutically targeting COX has been diminished over the past two decades due to significant complications of the cardiovascular and cerebrovascular systems caused by long-term use of COX-2 inhibitor drugs. New treatment strategies targeting the downstream prostanoid signaling receptors regulating the deleterious effects of COX cascade have been proposed. As such, a large number of selective small molecules that negatively or positively modulate these important inflammatory regulators have been evaluated for neuroprotection and other beneficial effects in various animal models of brain ischemia. These timely preclinical studies, though not yet led to clinical innovation, provided new insights into the regulation of inflammatory reactions in the ischemic brain and could guide drug discovery efforts aiming for novel adjunctive strategies, along with current reperfusion therapy, to treat acute brain ischemia with higher specificity and longer therapeutic window.

Cytokine status in patients with sepsis

Cytokines are specific proteins that are produced by lymphocytes. Cytokine production and release occurs rapidly and is rigorously controlled. Their activity is characterized by ensuring the interaction between cells and systems, regulation of inflammatory reactions and responsible for the development of autoimmune processes.Patients with sepsis develop immunosuppression, when immune deficiency can progress to immunoparalysis. Cytokines cause effects similar to manifestations of acute and chronic infectious diseases having an ability to cause inflammation (pro-inflammatory) or inhibit the inflammatory process development (anti-inflammatory).The aim of the work is to find out the dynamics of changes in the most important cytokines in patients with sepsis caused by diabetic foot syndrome.Materials and methods. A total of 146 patients with sepsis who received treatment in the Zaporizhzhia Purulent-Septic Center with diabetic foot beds between 2006 and 2019 were examined and followed up.Patients were distributed according to the forms of the disease: group 1 – 104 (71.2 %) patients with sepsis, group 2 – 42 (28.8 %) patients with septic shock. The average age of the patients was 62.8 ± 3.4 years, and the duration of type 2 diabetes mellitus was 12.3 ± 3.4 years. The groups were representative in terms of sex, age and concomitant pathology. The studies were conducted in dynamics: upon admission, on the 7–8th and 12–16th days of the postoperative period.Results. The disease in sepsis patients was caused by wet gangrene of the lower extremities which occurred in 84.6 % of cases (88 patients). In 16 patients (15.4 %), the complications were caused by foot phlegmon and extended osteomyelitis. The cause of sepsis in patients with septic shock was wet gangrene of the extremities in 100 % of cases. Postoperative mortality in sepsis patients was 18.3%, and in patients with septic shock – 70.8 %.The dynamics of changes in serum cytokines has been found to be indicative of these indicators imbalance which depends on the inflammatory process severity. The balance between cytokines is an important point in the regulation of inflammatory process onset and development. The course of the disease and its outcomes depend on this balance.Conclusions. Determining the cytokine status is of great prognostic value because the level of pro- and anti-inflammatory cytokines, their ratio in patients with sepsis and septic shock reflects the intensity of alterative-destructive and regenerative-restorative processes as well as the dynamics and progression of the disease.

Advances in IKBKE as a potential target for cancer therapy.

IKBKE (inhibitor of nuclear factor kappa‐B kinase subunit epsilon), a member of the nonclassical IKK family, plays an important role in the regulation of inflammatory reactions, activation and proliferation of immune cells, and metabolic diseases. Recent studies have demonstrated that IKBKE plays a crucial regulatory role in malignant tumor development. In recent years, IKBKE, an important oncoprotein in several kinds of tumors, has been widely found to regulate a variety of cytokines and signaling pathways. IKBKE promotes the growth, proliferation, invasion, and drug resistance of various cancers. This paper makes a detailed review that focuses on the recent discoveries of IKBKE in the malignant tumors, and puts forward that IKBKE is becoming an important therapeutic target for clinical treatment, which has been more and more realized.

Adenosine A2A Receptor Stimulation: A New Strategy for the Treatment of Periodontitis

Periodontitis is an unpleasant clinical condition in which an exaggerated inflammatory reaction occurs in the extravascular gingival tissue. Inflammatory cells release cytokines that amplify tissue inflammation and create the condition for periodontal tissue damage. Adenosine is a mediator that is released under several pathological conditions including ischemia and inflammation and participates in the regulation of inflammatory reaction. Among the several adenosine receptors, the adenosine A_2A subtype plays a key role in resolving gingival inflammation and in protecting the periodontal tissues from damage. PDRN (polydeoxyribonuclotide) binds selectively the A_2A subtype and exerts curative effect, suggesting that adenosine A_2A receptor stimulation might be an innovative strategy for the treatment of periodontitis.

Recent Advances in Obesity: The Role of Turmeric Tuber and Its Metabolites in the Prophylaxis and Therapeutical Strategies.

Obesity in the 21st century society became an important health problem, alarming both the scientists and medicine doctors around the world. That is why, the search for new drug candidates capable to reduce the body weight is of high concern. This contribution tends to collect current findings on the biochemistry of obesity and on the application of plants and in particular turmeric tuber - a commonly used spice - as an anti-obesity agent. Following an introduction on the biochemical characteristics of obesity, the description of Curcuma secondary metabolites, their pharmacological applications and a study on the plants' regulatory properties in obesity was summarized. Particular attention was paid to curcumin - the major metabolite present in the extracts of Curcuma spp., which is known to exhibit a variety of pharmacological actions. Also, the characteristics of some semisynthetic analogues of this ferulic acid derivative, characterized by a higher polarity and better bioavailability will be discussed. Numerous scientific papers treat on the influence of turmeric on weight loss. Additionally, some of them describe its anti-inflammatory properties. This important spice tends to fight the 21st century plague, which is an excessive weight gain, related to the development of metabolic syndrome, to the occurrence of cardiovascular problems and diabetes, and, in consequence, leading to a significant shortening of life span. As herein proven, the extracts of turmeric play an important role in the regulation of inflammatory reactions which are evoked in the overweight patients, helping them reduce the excess body weight.

Portulaca Extract Attenuates Development of Dextran Sulfate Sodium Induced Colitis in Mice through Activation of PPARγ.

Portulaca oleracea L. is a traditional Chinese medicine, which has been used as adjuvant therapy for inflammatory bowel disease (IBD). However, the mechanism of its activity in IBD still remains unclear. Since previous studies have documented the anti-inflammatory effect of peroxisome proliferator activated receptors-γ (PPAR-γ), Portulaca regulation of PPAR-γ in inflammation was examined in current study. Ulcerative colitis (UC) was generated by 5% dextran sulfate sodium (DSS) in mice and four groups were established as normal control, DSS alone, DSS plus mesalamine, and DSS plus Portulaca. Severity of UC was evaluated by body weight, stool blood form, and length of colorectum. Inflammation was examined by determination of inflammatory cytokines (TNF-a, IL-6, and IL-1a). Portulaca extract was able to attenuate development of UC in DSS model similar to the treatment of mesalazine. Moreover, Portulaca extract inhibited proinflammatory cytokines release and reduced the level of DSS-induced NF-κB phosphorylation. Furthermore, Portulaca extract restored PPAR-γ level, which was reduced by DSS. In addition, Portulaca extract protected DSS induced apoptosis in mice. In conclusion, Portulaca extract can alleviate colitis in mice through regulation of inflammatory reaction, apoptosis, and PPAR-γ level; therefore, Portulaca extract can be a potential candidate for the treatment of IBD.

Effect of saponins extracted from Panax japonicus on inhibiting cardiomyocyte apoptosis by AMPK/Sirt1/NF-κB signaling pathway in aging rats

To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1β, TNF-α, AMPK, p-AMPK, Sirt1, and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers, reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time, SPJ could significantly inhibit the protein expression of Bax, IL-1β, TNF-α and Ac-NF-κB p65, and increase the expression of Bcl-2, Bcl-2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its mechanisms may be related with the regulation of inflammatory reaction by AMPK/Sirt1/NF-κB signaling pathway.

Characterization of Fc gamma receptor IIb expression within abdominal aortic aneurysm

ObjectiveTo evaluate protein profiles and Fc gamma receptor IIb (FCGRIIB) expression in abdominal aortic aneurysm (AAA) compared to the expression in normal aortas. MethodsWe performed a protein array to study the protein expression profiles within AAA and normal aortic tissues. FCGRIIB was found to be significantly elevated in AAA samples. Quantitative PCR and Western blot analyses were performed to study the expression of FCGRIIB in AAA compared to that in normal aortic tissue. Immunohistochemistry was used to locate FCGRIIB and the B cell marker CD19 in AAA and normal aortas specimens. ResultsFCGRIIB was significantly elevated in AAA tissues in both mRNA (AAA vs. normal control: about 5.8 folds, p < 0.001) and protein levels (AAA vs. normal control: about 6.3 folds, p < 0.001). In AAA specimens, immunohistochemistry revealed that FCGRIIB localized to the area of inflammatory infiltrates, which consisted of CD 19+ B cells and other inflammatory cells. FCGRIIB and CD19 were undetectable in normal aortas. ConclusionsFCGRIIB was significantly elevated in AAA tissues compared to normal aortas. FCGRIIB may be involved in the pathogenesis of AAA by regulation of inflammatory reactions.

Inhibition of Neutrophil Adhesion and Antimicrobial Activity by Diluted Hydrosol Prepared from Rosa damascena.

Hydrosol prepared from the flowers of Rosa damascena (rose water) has been traditionally used for various health-related issues, including skin troubles such as erythema, itchiness, swelling. For the care of these skin troubles caused by microbial infection, both antimicrobial and antiinflammatory effects are required. Here, we investigated the effects of rose water on the growth of Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA), which cause skin infections, and on the function of neutrophils, which play a major role in the regulation of inflammatory reactions. To assess its modulatory effects on neutrophils, the effects of rose water against neutrophil adhesion response were evaluated. Rose water inhibited mycelial growth of C. albicans at a concentration of ca. 2.2%, and reduced viability of MRSA within 1 h. Rose water suppressed neutrophil activation induced by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-α), and N-formyl-Met-Leu-Phe (fMLP) at 5-15%. It also reduced the LPS- and TNF-α-induced cell surface expression of the adhesion-related molecule, cluster of differentiation (CD) 11b, but did not affect the migratory capacity of neutrophils with or without chemoattractant. These results suggest that rose water may reduce the pathogenicity of microbes, and attenuate neutrophil stimulation, which is involved in inflammatory responses. These findings suggest that rose water has a potential effect to inhibit skin inflammation caused by microbes.

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

ObjectiveTo investigate the role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH).MethodsThirty-six adult Sprague Dawley (SD) male rats were randomly divided into sham operation, ICH and zinc protoporphyrin (ZPP) group. Rats (except for the sham operation group) were given 50 μL stereotactic injection of autologous blood from the femoral artery into the caudate nucleus, to establish an ICH model. In addition, rats in the ZPP group were given 10 mg/kg intraperitoneal injection of ZPP. At day 3 postoperative, neurobehavioral changes and brain water content were evaluated, brain tissue HO-1 expression was detected with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), brain tissue apoptosis was evaluated with TUNEL method, Caspase 3, Caspase 8 and Caspase 9 activity were detected with colorimetric method, level of TNF-α, IL-1β, IL-6 and IL-8 were measured with the enzyme-linked immunosorbent assay (ELISA), while Bcl-2, Bax, p-NF-κB p65 and p-IκBα protein expression were detected with Western blot.ResultsICH group compared to sham operation: HO-1 positive rate and mRNA expression were increased, neurological deficit score and cell apoptosis rate were increased, Caspase 3, Caspase 8 and Caspase 9 activity were increased, level of TNF-α, IL-1β, IL-6 and IL-8 were increased, Bcl-2 expression was downregulated, Bax, p-NF-κB p65 and p-IκBα expression were upregulated. The differences were statistically significant (P<0.01). ZPP group compared to ICH: HO-1 positive rate and mRNA expression were decreased, neurological deficit score and cell apoptosis rate were decreased, Caspase 3, Caspase 8, Caspase 9 activity were decreased, level of TNF-α, IL-1β, IL-6 and IL-8 were decreased, Bcl-2 expression was upregulated, Bax, p-NF-κB p65 and p-IκBα expression were downregulated, and the differences were statistically significant (P<0.01).ConclusionHO-1 inhibitor, ZPP does have a protective effect on ICH rats. This might be due to its inhibition to the inflammatory reaction and neuronal cell apoptosis.