Levels Of MIP-1α Research Articles

Cigarette smoke condensate may disturb immune function with apoptotic cell death by impairing function of organelles in alveolar macrophages

Considering that cigarette smoke condensate (CSC) is primarily absorbed through the alveoli in the lungs, herein, we used a mouse alveolar macrophage cell line (MH-S cells). After 24 h exposure, CSC decreased dose-dependently cell viability accompanying an increase in intracellular ROS and NO level. CSC structurally or functionally damaged organelles including mitochondria, ER and lysosome and enhanced the expression of proteins related to apoptosis, ER stress and DNA damage accompanying an elevated proportion of annexin V-bound cells. Meanwhile, the expression of certain proteins related to mitochondrial dynamics (OPA1 and DRP1) and autophagy (ATG5) did not overall show significant dose-dependent change in cells exposed to CSC. More importantly, conversion of LC3-I to LC3B-II, a representative marker for autophagy, was also unclear. Considering that intracellular organelles work together in harmony to perform defense mechanism against foreign bodies, we investigated changes in immune response following CSC exposure. The level of IFN-γ and MIP-1α was elevated in CSC-exposed cells, whereas the MCP-1α level decreased. The expression of chemokine receptors (CD195 and CXCR2) and an adhesion molecule (CD54) increased by CSC treatment, the expression of certain antigen presentation-related proteins (MHC class II, CD40, and CD80) were also enhanced. Meanwhile, the expression of CD86, a co-stimulatory molecule for antigen presentation, dose-dependently decreased. In conclusion, we suggest that CSC may induce apoptotic cell death and disturbance in host defense mechanisms by impairing function of cellular components.

Oncostatin M promotes the osteogenic differentiation of mouse MC3T3‑E1osteoblasts through the regulation of monocyte chemotactic protein‑1.

The present study investigated the function of oncostatin M (OSM), which may be associated with monocyte chemotactic protein-1 (MCP-1), on mouse MC3T3-E1 osteoblast development and bone remodeling. Levels of MCP-1, macrophage inflammatory protein 1α (MIP1α) and regulated upon activation normal T cell expressed and secreted (RANTES) were measured by ELISA. Cell viability, migration and invasion abilities were detected by MTT, wound healing and Transwell assays, respectively. Western blotting was performed to detect levels of phosphorylated protein kinase B (Akt). Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to detect the levels of matrix metalloproteinases (MMP)-1, −2 and −3. The results demonstrated that OSM treatment significantly increased MCP-1 levels in a dose-dependent manner. Interleukin (IL)-1, also significantly increased MCP-1 levels; however, treatment with other cytokines, including IL-6, IL-11 and leukemia inhibitory factor did not affect MCP-1 levels to the same extent. In addition, OSM did not affect levels of the chemokines MIP1α and RANTES; indeed, only IL-1 significantly increased levels of MIP1α and RANTES. OSM treatment promoted the proliferation, migration and invasion in a dose-dependent manner, which were inhibited by MCP-1 silencing. The expression of phosphorylated-Akt, MMP-1, −2 and −3 were increased by OSM treatment; however, these increases were reversed following MCP-1 silencing. Collectively these data suggest that OSM promotes the differentiation of mouse MC3T3-E1 osteoblasts via regulation of MCP-1 expression. These results may therefore provide novel insights into bone repair and remodeling.

MIP-1α and MCP-1 as salivary biomarkers in periodontal disease

AbsractAimChemokines released by different host cells when exposed to the components of periodontopathic bacteria induce and maintain an inflammatory response in the periodontium. The aim of the study was to estimate the salivary levels of two chemokines, macrophage inflammatory protein-1 alpha (MIP-1α) and monocyte chemo attractant protein-1 (MCP-1) in health, gingivitis and periodontitis and to evaluate their role as reliable salivary biomarkers in discriminating gingivitis and periodontitis from health.MethodsA cross sectional study was designed to estimate the levels of MIP-1α and MCP-1 in whole unstimulated saliva from 75 patients who were divided into healthy (Group 1, n = 25), gingivitis (Group 2, n = 25) and chronic generalized periodontitis (Group 3, n = 25). MIP-1α and MCP-1 levels were estimated by using ELISA and were correlated with clinical parameters. ROC curve analysis was done to determine the sensitivity and specificity of these biomarkers in distinguishing periodontal disease from health.ResultsBoth the biomarkers were detected in all the saliva samples. There was a statistically significant difference in the concentration of both the analytes in Group 3 and Group 2 compared with Group 1 (p < 0.001). ROC curve analysis showed 100% sensitivity and specificity for MIP-1α and MCP-1 in discriminating periodontitis from health. For discriminating gingivitis from health, MIP-1α had a higher sensitivity and specificity (100% & 88% respectively) compared to MCP-1(84.1% & 80% respectively).ConclusionThere is a substantial increase in the concentration of both MIP-1α and MCP-1 with increasing severity of periodontal disease. Both the analytes showed promising results as biomarkers for discriminating periodontal disease from health.

An ethanolic extract of the aerial part of Siegesbeckia orientalis L. inhibits the production of inflammatory mediators regulated by AP-1, NF-κB and IRF3 in LPS-stimulated RAW 264.7 cells.

Herba Siegesbeckiae (HS, the dried aerial part of Siegesbeckia orientalis L.) is a commonly used traditional Chinese medicinal herb for treating inflammatory diseases. HS has been reported to exert anti-inflammatory effects by inhibiting the MAPKs and NF-κB pathways, the downstream effectors of TLR4 signalling. This study aims to further investigate the involvement of TLR4 signalling cascades in the effects of an ethanolic extract of HS (HS for short) on inflammatory mediators in murine macrophages. HS was extracted using 50% ethanol. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were used as the cell model. ELISA was used to detect cytokine/chemokine secretion. Real time-PCR and immunoblotting were used to examine mRNA and protein levels, respectively. We observed that HS dose-dependently inhibited the secretion of PGE2, MCP-1, MIP-1α and RANTES, and down-regulated mRNA levels of iNOS, COX-2, IL-1β, IL-6, TNF-α, mPGES-1, MCP-1, MIP-1α and RANTES in LPS-stimulated RAW264.7 cells. HS did not affect the protein levels of TAK1, TBK1, PI3K, Akt, IKK, c-Jun, c-Fos and IRF3, while, dose-dependently decreased levels of their phosphorylated forms. The protein levels of IRAK1 and IRAK4 were upregulated, while those of TRAF6 and TRAF3 were downregulated by HS. Moreover, the nuclear protein levels of AP-1, NF-κB and IRF3 were dose-dependently decreased by HS. These results indicate that suppression of the IRAK4/MAPKs/AP-1, IRAK4/MAPKs/NF-κB, IRAK4/PI3K/NF-κB and TRAF3/TBK1/IRF3 pathways is associated with the inhibitory effects of HS on inflammatory mediators in LPS-stimulated RAW264.7 cells. This study provides a pharmacological basis for the clinical application of this herb in the treatment of inflammatory disorders.

Serum cytokine responses in Rickettsia felis infected febrile children, Ghana

The intracellular pathogen Rickettsia felis causes flea-borne spotted fever and is increasingly recognized as an emerging cause of febrile illness in Africa, where co-infection with Plasmodium falciparum is common. Rickettsiae invade endothelial cells. Little is known, however, about the early immune responses to infection. In this study, we characterize for the first time the cytokine profile in the acute phase of illness caused by R. felis infection, as well as in plasmodial co-infection, using serum from 23 febrile children < 15 years of age and 20 age-matched healthy controls from Ghana. Levels of IL-8 (interleukin-8), IP-10 (interferon-γ-induced protein-10), MCP-1 (monocyte chemotactic protein-1), MIP-1α (macrophage inflammatory protein-1α) and VEGF (vascular endothelial growth factor) were significantly elevated in R. felis mono-infection; however, IL-8 and VEGF elevation was not observed in plasmodial co-infections. These results have important implications in understanding the early immune responses to R. felis and suggest a complex interplay in co-infections.

Anti-inflammatory activity of the piperazino-enaminone JODI-19 in vitro and in vivo

Abstract Data to characterize novel anti-inflammatory agent enaminone E121 have shown a marked decrease in the release of pro-inflammatory cytokines in macrophages stimulated with lipopolysaccharide (LPS) compared to the control (DMSO) group. Literature has described that when an N-alkylated piperazine motif is added to the terminal end of the lead compound, it is able to increase the CCR2 antagonistic activity. We hypothesized that incorporating the N-alkylated piperazine motif into the existing E-121 enaminone pharmacophore could lead to a ligand with dual functionality as a cytokine inhibitor and chemokine receptor antagonist. The resultant series (JODI) were studied in vitro, and data suggest they can suppress TNF-alpha and IL-6 in a dose-dependent manner, superior to that of dexamethasone. Additionally, macrophages stimulated with chemokine MCP-1 and treated with JODI compounds, (but not E121), are able to block CCR2 signaling as evidenced by decreased total ERK1/2. To determine if JODI-19 has activity in vivo, it was utilized in a mouse model of hemarthrosis to assess decreased inflammation as evidenced by local cytokine suppression. In a pilot study, FIX−/−mice were subjected to hemarthrosis induction with or without JODI administration. At different timepoints from four hours to four weeks after hemarthrosis, synovial fluid was collected by lavage for multiple cytokine analyses. Administration of JODI-19 significantly decreased TNFα, IL-1α, MCP-1 and MIP-1α levels in the synovial fluid. As such, JODI-19 may be a novel approach to better manage hemophilia arthropathy and its associated bone damage.

Decreased macrophage inflammatory protein (MIP)-1\u03b1 and MIP-1\u03b2 increase the risk of developing nasopharyngeal carcinoma

BackgroundThe association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.MethodsThe serum levels of 33 inflammatory cytokines were first measured in a hospital-based case–control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case–control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein–Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test.ResultsThe levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1β in the highest categories were associated with a decreased risk of NPC in both the case–control study (MIP-1α: OR = 0.49, 95% CI = 0.26–0.95; MIP-1β: OR = 0.47, 95% CI = 0.22–1.00) and the nested case–control study (MIP-1α: OR = 0.13, 95% CI = 0.03–0.62; MIP-1β: OR = 0.20, 95% CI = 0.04–0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case–control study (MIP-1α: OR = 16.28, 95% CI = 7.11–37.23; MIP-1β: OR = 12.86, 95% CI = 5.9–28.05) and the nested case–control study (MIP-1α: OR = 86.12, 95% CI = 10.58–701.03; MIP-1β: OR = 115.44, 95% CI = 13.92–957.73).ConclusionsDecreased preclinical MIP-1α and MIP-1β levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine.

In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1β, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1β in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.

A study on the regenerative effect of platelet-rich plasma on experimentally induced hepatic damage in albino rats.

Hepatic fibrosis is a worldwide health problem with significant morbidity and mortality. Currently, there is no effective therapy for hepatic fibrosis. The present study was aimed to evaluate the possible regenerative effect of platelet-rich plasma (PRP) against thioacetamide (TAA)-induced hepatic damage. Eighty albino rats were included; 40 were used for PRP preparation and 40 were randomly divided into 4 groups: group I (control group); group II (PRP control); group III (TAA-intoxicated by a dose of 200 mg/kg body mass, intraperitoneally, twice weekly for 7 weeks), and group IV (TAA intoxicated + PRP treated). Macrophage inflammatory protein-1α (MIP-1α) and cyclic adenosine monophosphate (cAMP) were immunoassayed in addition to peroxinitrite level, NADPH-quinone oxidoreductase-1 (NQO1) enzyme activity, and liver function. PRP treatment showed significant improvement in hepatic function, and decreased MIP-1α and peroxinitrite levels. Meanwhile, significant increase in NQO1 enzyme activity and cAMP level were observed. The histopathological results confirmed the laboratory results with improvement of hepatic architecture except for some inflammatory cellular infiltrates. This study shows that PRP has the ability to protect against TAA-induced liver damage, possibly by improving redox status, liver histopathological architecture, and disruption of the inflammatory and fibrotic response induced by TAA.

Infection by HTLV-1 Is Associated With High Levels of Proinflammatory Cytokines in HIV-HCV–Coinfected Patients

HIV, hepatitis C virus (HCV), and human T-cell lymphotropic virus type 1 (HTLV-1) share the same routes of infection, making coinfection by these viruses a frequent finding in endemic areas. However, there is scarce information on the clinical/immunological consequences of triple infection. Coinfection by HTLV-1 is able to modulate cytokine's production in patients with HIV, but there are no data on the immune response of HIV-HCV-HTLV-1-infected patients. We compared the plasma levels of 25 different cytokines in patients with HIV-HCV, according to their serostatus to HTLV-1 infection. Eligible patients should be on stable highly active antiretroviral therapy and have undetectable HIV-1 plasma viral load for, at least, 12 months. Cytokines levels were also evaluated by CD4 cells count, rates of sustained virological response (SVR) to previous HCV treatment, frequency of spontaneous HCV clearance, and HCV/IFN-λ3 genotypes. Twenty-five patients (15 coinfected by HIV and HCV, 10 coinfected by HIV, HCV, and HTLV-1) were evaluated. Among the triply infected group, 3 had undetectable HCV viremia (spontaneous clearance). All but one remaining patients were previously treated for HCV, with similar SVR rates (∼29%). Cytokines levels did not differ per HCV/IFN-λ3 genotypes, mean CD4 cells count, age, sex, or SVR. However, patients coinfected by HTLV-1 showed significantly higher levels of IL-1b, IL-2, TNF-α, IFN-γ, MIP-1α, RANTES, and interferon-induced protein 10 (IP-10) than HIV-HCV-coinfected ones. Patients presenting HCV spontaneous clearance had the highest levels of cytokines. Coinfection by HTLV-1 increases the plasma levels of proinflammatory cytokines of patients with HIV-HCV and can influence the outcomes of coinfected patients.

Nicorandil and theophylline can protect experimental rats against complete Freund's adjuvant-induced rheumatoid arthritis through modulation of JAK/STAT/RANKL signaling pathway

Signaling pathways are interesting fields of study of pathogenesis and treatment trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day) and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) / RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling pathway. Four sets of experiments were performed. First, effect of test agents on normal animals was evaluated. Second, effect of test agents was evaluated on Complete Freund's Adjuvant (CFA; 0.3ml, s.c.)-induced RA to investigate anti-arthritic effect. Third, effect of test agents was evaluated on growth hormone (GH; 2mg/kg/day, s.c.)-induced stimulation of JAK/STAT/RANKL/cytokine signaling pathway to investigate the role of this signaling pathway in their anti-arthritic effect. Fourth, the effect of test agents was performed on CFA/GH-induced RA. To fulfill this purpose, serum anti-citrullinated peptide antibody (ACPA), interleukin-6 (IL-6), and cartilage oligomeric matrix protein (COMP), together with tissue JAK2, STAT3, RANKL, inducible and endothelial nitric oxide synthases (iNOS and eNOS) as well as macrophage inflammatory protein (MIP1α) were estimated using ELISA, Western blotting and PCR techniques, confirmed by a histopathological study. Test agents significantly corrected JAK2, STAT3, RANKL and IL-6 values in animals receiving GH. Additionally, test agents could correct ACPA, IL-6, COMP, JAK2, STAT3, RANKL, iNOS, eNOS and MIP1α levels compared with the respective CFA or CFA/GH controls. These results conclude that nicorandil and theophylline have good anti-arthritic effects related to modulation of JAK/STAT/RANKL signaling pathway. Further clinical trials are claimed.

Evaluation of Chemokines in the Gingival Crevicular Fluid of Children with Down Syndrome.

AimThe goal of the study was to detect the presence of macrophage inflammatory protein (MIP)-1α and MIP-1β and to estimate their levels in gingival crevicular fluid (GCF) of children with Down syndrome.Materials and methodsMIP-1α and MIP-1β levels were estimated in GCF samples of 20 healthy and 20 Down syndrome individuals. Gingival status was assessed by measuring the gingival index (GI), plaque index (PI), clinical attachment level (CAL), and probing pocket depth (PPD).The GCF samples were obtained from the subjects and MIP-1α and MIP-1β levels were quantified by enzyme-linked immunosorbent assay (ELISA).ResultsThe mean MIP-1α concentrations in healthy and Down syndrome individuals were 209 and 1411 pg/μL respectively, and MIP-1α levels were 342 and 1404 pg/μL respectively.The levels of MIP-1α and MIP-1β in the GCF of subjects with Down syndrome were significantly higher than in the healthy individual, and statistically significant differences were present among the two groups.ConclusionThe GCF showed dynamic changes according to the severity of periodontal disease, and the levels of MIP-1α and MIP-1β had a strong relationship with clinical parameters. The MIP-1α and MIP-1β can therefore be considered as novel biomarkers in the biological mechanism underlying the patho-genesis of periodontal disease.How to cite this article: Reddy VK, Kommineni NK, Padakandla P, Togaru H, Indupalli JP, Nanga SP. Evaluation of Chemokines in the Gingival Crevicular Fluid of Children with Down Syndrome. Int J Clin Pediatr Dent 2018;11(4):288-293.

Serum Cytokine Profiles in Patients with Dengue Fever at the Acute Infection Phase.

Background Dengue virus (DENV) is transmitted by mosquito and has been circulating in Guangdong, China, for over 30 years. Dengue infection causes mild to severe disease symptoms in human. Cytokine profiles were suggested to be crucial especially during the acute stage in the dengue infection. Aim To determine the cytokine profiles at the acute stage in patients with primary or secondary dengue infection in Guangzhou city in the 2014 outbreak. Methods We investigated 23 inflammatory cytokines in serum collected from dengue-infected patients and analyzed their correlations with their clinical indexes. Results The concentrations of CXCL9, IP-10, CXCL11, IL-8, IL-10, and CCL2 in serum were significantly higher in the groups of DENV-infected patients during the first two weeks than those of control group while CCL17 and CXCL5 showed lower expression level in the patients. Among these cytokines, CXCL9, CCL17, and CXCL5 showed statistical difference between the groups of primary and secondary infections. The platelet count and lactate dehydrogenase were correlated with the level of CCL17 and MIP-1α/CXCL5, respectively, in the group of secondary infection. Conclusions We determined the cytokine profiles in serum of the patients during the 2014 dengue outbreak. The expression of specific cytokines was associated with the secondary infection.

The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial.

Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans, cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis.

Our study of the changes in cytokine profile in blood serum and in the spinal cord after traumatic spinal cord injury (SCI) has shown that an inflammatory reaction and immunological response are not limited to the CNS, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples [MIP-1α, interleukin 1 (IL-1) α, IL-2, IL-5, IL-1β, MCP-1, RANTES]. There were also changes in the levels of MIP-1α, IL-1α, IL-2, IL-5, IL-18, GM-colony-stimulating factor, IL-17α, IFN-γ, IL-10, IL-13, MCP-1, and GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited after SCI and show significant changes in the concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities.

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis.

BackgroundCocaine use disorder (CUD) is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation.MethodsThe study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain). The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group) and matched control subjects (N = 81, control group). Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNγ), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-17α (IL-17α), macrophage inflammatory protein 1α (MIP-1α) and transforming growth factor α (TGFα) levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables.ResultsWhile 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients displayed greater cocaine symptom severity when they were diagnosed with psychiatric comorbidity. Regarding inflammatory factors, we observed significantly lower plasma levels of IL-17α (p < 0.001), MIP-1α (p < 0.001) and TGFα (p < 0.05) in the cocaine group compared with the levels in the control group. Finally, there was a significant primary effect of dual diagnosis on the plasma concentrations of TGFα (p < 0.05) in the cocaine group, and these levels were lower in patients with dual diagnosesDiscussionIL-17α, MIP-1α and TGFα levels are different between the cocaine and control groups, and TGFα levels facilitate the identification of patients with dual diagnosis. Because TGFα reduction is associated with enhanced responses to cocaine in preclinical models, we propose TGFα as a potential biomarker of complex CUD in humans.

Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells

Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs). After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39.2% to 53.4%) to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. A greater production of proinflammatory cytokines in hAECs was elicited at later passages together with earlier peaking at 24 hours post infection of IL-6, MIP-1α, and MCP-1 levels. Viral replication capacity in hAECs maintained at similar levels throughout the 35 passages. In conclusion, during the serial infections of hAECs by influenza A(H7N9) virus, enhanced binding of virion to cell receptors with subsequent stronger innate cell response were noted, but no enhancement of viral replication could be observed. This indicates the existence of possible evolutional hurdle for influenza A(H7N9) virus to transmit efficiently from human to human.

A green tea polyphenol epigallocatechin-3-gallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines

Spinal cord injury (SCI) is a debilitating condition which is characterized by an extended secondary injury due to the presence of inflammatory local milieu. Epigallocatechin gallate (EGCG) appears to possess strong neuroprotective properties. Here, we evaluated the beneficial effect of EGCG on recovery from SCI. Male Wistar rats were given either EGCG or saline directly to the injured spinal cord and thereafter a daily IP injection. Behavior recovery was monitored by BBB, plantar, rotarod and flat-beam tests. The levels of inflammatory cytokines were determined on days 1, 3, 7, 10 and 14 after SCI. Additionally, NF-κB pathway activity was evaluated. The results demonstrated that EGCG-treated rats displayed a superior behavioral performance in a flat beam test, higher axonal sprouting and positive remodelation of glial scar. Cytokine analysis revealed a reduction in IL-6, IL2, MIP1α and RANTES levels on days 1 and 3, and an upregulation of IL-4, IL-12p70 and TNFα 1 day following SCI in EGCG-treated rats. Treatment with EGCG was effective in decreasing the nuclear translocation of subunit p65 (RelA) of the NF-κB dimer, and therefore canonical NF-κB pathway attenuation. A significant increase in the gene expression of growth factors (FGF2 and VEGF), was noted in the spinal cord of EGCG-treated rats. Further, EGCG influenced expression of M1 and M2 macrophage markers. Our results have demonstrated a therapeutic value of EGCG in SCI, as observed by better behavioral performance measured by flat beam test, modulation of inflammatory cytokines and induction of higher axonal sprouting.

Cardioprotective effect of Malva sylvestris L. in myocardial ischemic/reprefused rats

PurposeThe present investigation evaluated the cardioprotective effect of Malva sylvestris L. (MS) on myocardial ischemic/reperfusion (MI/R) in rats. MethodsAll animals were divided into four groups: the sham operated group, ischemia/reperfusion group (MI/R), and the MS (250 and 500mg/kg) treated groups, who received MS 250 and 500mg/kg intragastrically for 15 consecutive days, respectively. At the end of the protocol, concentrations of aspartate transaminase (AST), creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH) were estimated in serum and the concentrations of other parameters, such as C-reactive protein, macrophage inflammatory protein 1 alpha (MIP-1α), and nitric oxide (NO) were also estimated in the blood. Tissue homogenate concentrations of inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interlukin-1β (IL-1β), IL-10 and IL-6 as well as oxidative stress parameters, such as lipid peroxidation, catalase, and superoxide dismutase were estimated in MI/R rats. ResultSignificant decreases (p<0.01) in AST, LDH, and CK-MB levels were observed in the MS-treated group compared with those in the MI/R group. C-reactive protein and MIP-1α levels decreased in the MS-treated group compared with those in the MI/R group. Plasma NO level was significantly enhanced in the MS-treated group than in the MI/R group. Moreover, treatment with MS significantly reduced TNF-α, IL-1β, and IL-6 levels and increased IL-10 levels in the MS group compared with the MI/R group. Treatment with MS also attenuated the altered oxidative stress parameters in MI/R rats. ConclusionThe present results indicate the cardioprotective effects of MS of reducing oxidative stress and the inflammatory response in MI/R rats.

Suitability of saliva for Tuberculosis diagnosis: comparing with serum

BackgroundIn the search for fast, simple and better ways for diagnosis of tuberculosis (TB), there is need to discover and evaluate new biomarkers that are found in samples other than sputum to determine their effectiveness. This study examined the utility of saliva vis-a-vis serum by evaluating levels of biomarkers found in saliva and serum from TB suspects.MethodsStudy enrolled tuberculosis suspects. Sputum MGIT was used as the gold standard for active TB. Quantiferon gold-In tube assay was done to identify exposure to Mycobacterium tuberculosis (M.tb). Multiplex assay was run for 10 markers using a 10 plex customized kit from Bio-Rad Laboratories.ResultsThere was a significant difference between saliva and serum marker levels. Saliva had significantly higher levels of GM-CSF and VEGF. Serum had higher levels of MIP-1a, b, TNF-a, G-CSF and IFN-g. Serum levels of IL-6, VEGF and TNF-a were significantly different between participants with active TB disease and those with other respiratory diseases.ConclusionSalivary TB biomarkers are worth the search to evaluate their ability to differentiate between TB disease states for generation of a non invasive point of care test for TB diagnosis.