Search results for: inflammatory cytokine

Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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Authors: Bhupendra Kumar Poudel, Sadhana Amatya, Tirtha Maiya Shrestha, Bharatmani Pokhrel, Mohan Prasad Amatya

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Background: H. salicifolia is a dense, branched, multipurpose, deciduous, nitrogen fixing, thorny willow-like small to moderate tree, restricted to the Himalaya. Among the two species of Nepal (Hippophae salicifolia and H. tibetana), it has been traditionally used as food additive, anticancer (bark), and treating toothache, tooth inflammation (anti-inflammatory) and radiation injury; while people of Western Nepal have largely undermined its veiled treasure by using it for fuel, wood and soil stabilization only. Therefore, the main objective of this study was to explore biological properties (analgesic, antidiabetic, cytotoxic and anti-inflammatory properties of this plant. Methodology: The transverse section of leaves and stems were viewed under microscope. Extracts obtained from soxhlation subjected to tests for phytochemical and biological studies. Rats (used to study antidiabetic and anti-inflammatory properties) and mice (used to study analgesic, CNS depressant, muscle relaxant and locomotor properties) were assumed to be normally distributed; then ANOVA and post hoc tukey test was used to find significance. The data obtained were analyzed by SPSS 17 and Excel 2007. Results and Conclusion: Pharmacognostical analysis revealed the presence of long stellate trichomes, double layered vascular bundle 5-6 in number and double layered compact sclerenchyma. The preliminary phytochemical screening of the extracts was found to exhibit the positive reaction tests for glycoside, steroid, tannin, flavonoid, saponin, coumarin and reducing sugar. The brine shrimp lethality bioassay tested in 1000, 100 and 10 ppm revealed cytotoxic activity inherent in methanol, water, chloroform and ethyl acetate extracts with LC50 (μg/ml) values of 61.42, 99.77, 292.72 and 277.84 respectively. The cytotoxic activity may be due to presence of tannins in the constituents. Antimicrobial screening of the extracts by cup diffusion method using Staphylococcus aereus, Escherichia coli and Pseudomonas aeruginosa against standard antibiotics (oxacillin, gentamycin and amikacin respectively) portrayed no activity against the microorganisms tested. The methanol extract of the stems and leaves showed various pharmacological properties: and antidiabetic, anti-inflammatory, analgesic [chemical writhing method], CNS depressant, muscle relaxant and locomotor activities in a dose-dependent fashion, indicating the possibility of the presence of different constituents in the stems and leaves responsible for these biological activities. All the effects when analyzed by post hoc tukey test were found to be significant at 95% confidence level. The antidiabetic activity was presumed to be due to flavonoids present in extract. Therefore, it can be concluded that this plant’s secondary metabolites possessed strong antidiabetic, anti-inflammatory and cytotoxic activity which could be isolated for further investigation.

Keywords: Hippophae salicifolia, constituents, antidiabetic, inflammatory, brine shrimp

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Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal

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Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.

Keywords: bariatric, biomarkers, inflammation, laparoscopy

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Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Nahed O. Bawakid, Walied M. Alarif

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With regard to the uniqueness of the red algae of the genus Laurencia as the source of C₁₅-acetogenins, along with the diversity of biological applications; the acetogenin content of the Red Sea L. obtusa was investigated. Fractionation and purification of the CH₂Cl₂/MeOH extract were done by applying several chromatographic techniques, including column and preparative thin-layer chromatography; followed by a series of ¹H nuclear magnetic resonance measurements to give rise of some interesting notes. A new rare chloroallene-based C₁₅ acetogenin, laurentusenin (1) along with a new furan ring containing C₁₅ acetogenin, laurenfuresenin (2), were isolated from the red alga L. obtusa. Comparing 1D and 2D NMR, MS, UV and IR spectral data for the new isolated compounds with the reported bromoallene containing acetogenins spectral data was played the crucial role for characterization of their hemical structures. The apoptosis induced by these two compounds was demonstrated by DNA fragmentation assay and microscopic observation. These observations suggest that (1) and (2) may be involved in regulation of programmed death in the initiation and propagation of inflammatory responses. The isolated metabolite (1) showed unusual substituted allene side chain, while (2) inserted furan ring as a new acetogenin nucleus.

Keywords: cyclic enyne, anti-inflammatory, fatty acids, marine algae, halogenations

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Authors: Mazdak Ganjalikhani, Mohamad Namgar, Alireza Peyman

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Introduction: The present study was carried out to measure the levels of inflammatory markers Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in tear of keratoconus patients and investigate their relationship with the severity of keratoconus. Materials and Methods: This study was performed on 81 patients with keratoconus (cases) and 85 healthy individuals (controls) who were selected through the convenience sampling method from patients visiting the Feiz Ophthalmology Hospital affiliated with the Isfahan University of Medical Sciences. Tear levels of IL-6 and TNF-α were measured after collecting the patient's tears from the lower eyelid through the Schirmer I method using a filter paper (Schirmer tear test strip) without anesthesia. Findings: The mean levels of IL-6 and TNF-α were 26.77±8.16 and 34.58±9.82 in the control group and 103.22±51.94, and 183.76±54.61 in the case group, respectively, indicating a significant difference between two groups (p<0.05). In addition, there was a significant relationship between the severity of the keratoconus and the mean levels of TNF-α and IL-6 in the case group (p<0.05). Conclusion: According to the results, the mean levels of IL-6 and TNF-α were higher in keratoconus cases than in the controls, and the disease severity was significantly associated with the levels of inflammatory markers IL-6 and TNF-α.

Keywords: keratoonus, cataract, tumor necrotic factor, interleukin 6

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Authors: Sally Ibrahim, Mohamed Hedia, Mohamed Taqi, Mohamed Derbala, Karima Mahmoud, Youssef Ahmed, Sayed Ismail, Mohamed El-Belely

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The identification and quantification of serum microRNA (miRNA) from mares with endometritis might serve as useful and implementable clinical biomarkers for the early diagnosis of endometiritis. Aims of the current study were (I) to study the expression pattern of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205, and (II) to determine the levels of interleukin 6 (IL-6), prostaglandins (PGF₂α and PGE₂), in the serum of Arabian mares with healthy and abnormal uterine status (endometritis). This study was conducted on 80 Arabian mares (4-14 years old). Mares were divided into 48 sub-fertile mares suspected of endometritis and 32 fertile at stud farms. The criteria for mares to be enrolled in the endometritis group were that they had been bred three or more times unsuccessfully in the breeding season or had a history of more than one year of reproductive failure. In addition, two or more of the following criteria on a checklist were present: abnormal clinical findings, transrectal ultrasonographic uterine examination showed abnormal fluid in the uterus (echogenic or ≥2 cm in diameter), positive endometrial cytology; and bacterial and/or fungal growth. Serum samples were collected for measuring IL-6, PGF₂α, and PGE₂ concentrations, as well as serum miRNA isolation and quantitative real-time PCR. Serum concentrations of IL-6, PGE₂, and PGF₂α were higher (P ≤ 0.001) in mares with endometritis compared to the control healthy ones. The expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 increased (P≤0.001) in mares with endometritis compared to the control ones. To the best of our knowledge, this is the first study that revealed that serum miRNA and serum inflammatory mediators (IL-6, PGE₂, and PGF₂α) could be used as non-invasive gold standard biomarkers, and therefore might be served as an important additional diagnostic tool for endometritis in Arabian mares. Moreover, estimation of the serum concentrations of serum miRNA, IL-6, PGE₂, and PGF₂α is a promising recommended tool during the breeding soundness examination in mares.

Keywords: Arabian Mares, endometritis, inflammatory mediators, serum miRNA

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Yori Gidron, Maartje Mol, Norbert Foudraine, Frits Van Osch, Joop Van Den Bergh, Moshe Farchi, Maud Straus

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Background: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-COV2), which began in 2019, also known as Covid-19, has infected over 136 million people and tragically took the lives of over 2.9 million people worldwide. Many of the complications and deaths are predicted by the inflammatory “cytokine storm.” One way to progress in the prevention of death is by finding a predictive and protective factor that inhibits inflammation, on the one hand, and which also increases anti-viral immunity on the other hand. The vagal nerve does precisely both actions. This study examined whether vagal nerve activity, indexed by heart-rate variability (HRV), predicts survival in patients with Covid-19. Method: We performed a pseudo-prospective study, where we retroactively obtained ECGs of 271 Covid-19 patients arriving at a large regional hospital in The Netherlands. HRV was indexed by the standard deviation of the intervals between normal heartbeats (SDNN). We examined patients’ survival at 3 weeks and took into account multiple confounders and known prognostic factors (e.g., age, heart disease, diabetes, hypertension). Results: Patients’ mean age was 68 (range: 25-95) and nearly 22% of the patients had died by 3 weeks. Their mean SDNN (17.47msec) was far below the norm (50msec). Importantly, relatively higher HRV significantly predicted a higher chance of survival, after statistically controlling for patients’ age, cardiac diseases, hypertension and diabetes (relative risk, H.R, and 95% confidence interval (95%CI): H.R = 0.49, 95%CI: 0.26 – 0.95, p < 0.05). However, since HRV declines rapidly with age and since age is a profound predictor in Covid-19, we split the sample by median age (40). Subsequently, we found that higher HRV significantly predicted greater survival in patients older than 70 (H.R = 0.35, 95%CI: 0.16 – 0.78, p = 0.01), but HRV did not predict survival in patients below age 70 years (H.R = 1.11, 95%CI: 0.37 – 3.28, p > 0.05). Conclusions: To the best of our knowledge, this is the first study showing that higher vagal nerve activity, as indexed by HRV, is an independent predictor of higher chances for survival in Covid-19. The results are in line with the protective role of the vagal nerve in diseases and extend this to a severe infectious illness. Studies should replicate these findings and then test in controlled trials whether activating the vagus nerve may prevent mortality in Covid-19.

Keywords: Covid-19, heart-rate Variability, prognosis, survival, vagal nerve

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Authors: Mariam G. Eshak, Ahmed Abbas, M. I. El-Sabry, M. M. Mashaly

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This investigation was conducted to determine the physiological response and evaluate the expression of inflammatory and cell death genes and DNA damage induced by endotoxic shock in laying hens. Endotoxic shock was induced by a single intravenous injection of 107 Escherichia coli (E. coli,) colony/hen. In the present study, 240 forty-week-old laying hens (H&N) were randomly assigned into 2 groups with 3 replicates of 40 birds each. Hens were reared in battery cages with wire floors in an open-sided housing system under natural conditions. Housing and general management practices were similar for all groups. At 42-wk of age, 45 hens from the first group (15 replicate) were infected with E. coli, while the same number of hens from the second group was injected with saline and served as a control. Heat shock protein-70 (HSP-70) expression, plasma corticosterone concentration, body temperature, and the gene expression of bax, caspase-3 activity, P38, Interlukin-1β (Il-1β), and tumor necrosis factor alpha (TNF-α) genes and DNA damage in the brain and liver were measured. Hens treated with E. coli showed significant (P≤0.05) increase of body temperature by 1.2 ᴼC and plasma corticosterone by 3 folds compared to the controls. Further, hens injected with E.Coli showed markedly over-expression of HSP-70 and increase DNA damage in brain and liver. These results were synchronized with activating cell death program since our data showed significant (P≤0.05) high expression of bax and caspase-3 activity genes in the brain and liver. These results were related to remarkable over-inflammation gene expression of P38, IL-1β, and TNF-α in brain and liver. In conclusion, our results indicate that endotoxic shock induces inflammatory physiological response and triggers cell death program by promoting P38, IL-1β, and TNF-α gene expression in the brain and liver.

Keywords: chicken, DNA damage, Escherichia coli, gene expression, inflammation

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Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Kelly E. Tow, Peter Caputi, Claudia Rogge, Thomas Lee, Simon R. Knowles

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Inflammatory Bowel Disease (IBD) is a serious chronic health condition, characterised by inflammation of the gastrointestinal tract. Individuals with active IBD experience severe abdominal symptoms, which can adversely impact their physical and mental health, as well as their quality of life (QoL). Given that stress may exacerbate IBD symptoms and is frequently highlighted as a contributing factor for the development of psychological difficulties and poorer QoL, it is vital to investigate stress-management strategies aimed at improving the lives of those with IBD. The present study extends on the limited research in IBD cohorts by exploring the role of dispositional mindfulness and its impact on psychological well-being and QoL. The study examined how disease activity and dispositional mindfulness were related to psychological distress and QoL in a cohort of IBD patients. The potential role of dispositional mindfulness as a moderator between stress and anxiety, depression and QoL in these individuals was also examined. Participants included 47 patients with a clinical diagnosis of IBD. Each patient completed a series of psychological questionnaires and was assessed by a gastroenterologist to determine their disease activity levels. Correlation analyses indicated that disease activity was not significantly related to psychological distress or QoL in the sample of IBD patients. However, dispositional mindfulness was inversely related to psychological distress and positively related to QoL. Furthermore, moderation analyses demonstrated a significant interaction between stress and dispositional mindfulness on anxiety. These findings demonstrate that increased levels of dispositional mindfulness may be beneficial for individuals with IBD. Specifically, the results indicate positive links between dispositional mindfulness, general psychological well-being and QoL, and suggest that dispositional mindfulness may attenuate the negative impacts of stress on levels of anxiety in IBD patients. While further research is required to validate and expand on these findings, the current study highlights the importance of addressing psychological factors in IBD and indicates support for the use of mindfulness-based interventions for patients with the disease.

Keywords: anxiety, depression, dispositional mindfulness, inflammatory bowel disease, quality of life, stress

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Authors: Jihoon Yang, Jeong II Choi

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Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

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Authors: Basuki Supartono

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Introduction: Diabetic wound risks limb amputation, and the healing remains challenging. Chronic Hyperglycemia caused the insufficient inflammatory response and impaired ability of the cells to regenerate. Tissue Engineering Technique is mandatory. Methods: Tissue engineering (TE)-based therapy Utilizing mononuclear cells, plasma rich platelets, and collagen applied on the damaged tissue Results: TE technique resulting in acceptable outcomes. The wound healed completely in 2 months. No adverse effects. No allergic reaction. No morbidity and mortality Discussion: TE-based therapy utilizing mononuclear cells, plasma rich platelets, and collagen are safe and comfortable to fix damaged tissues. These components stop the chronic inflammatory process and increase cells' ability for regeneration and restoration of damaged tissues. Both of these allow the wound to regenerate and heal. Conclusion: TE-based therapy is safe and effectively treats unhealed diabetic lesion.

Keywords: diabetic foot lesion, tissue engineering technique, wound healing, stemcells

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Mustafa Metin Donma, Orkide Donma

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Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

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In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

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Authors: Marina G. Galitskaya, Svetlana G. Makarova, Andrey P. Fisenko.

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Children on medication-induced immunosuppression are at high risk of developing severe course infectious diseases. Therefore, preventive vaccination is especially important for these children. However, due to the immunosuppressive effects of treatment for the underlying disease, the effectiveness of vaccination may decrease below the protective level. In a multidisciplinary children's medical center, post-vaccination immunity was studied in 79 children aged 4-17 years. The children were divided into 2 groups: Group 1 (38 children) with kidney pathology (Nephrotic Syndrome) and Group 2 (41 children) with inflammatory bowel diseases (Ulcerative Colitis, Crohn's Disease). Both groups of children were vaccinated according to the national vaccination calendar and received immunosuppressive therapy (prednisolone, methotrexate, cyclosporine, and other drugs) for at least 1 year. Using the enzyme-linked immunosorbent assay method, specific IgG antibodies to vaccine-preventable infections were determined: measles, rubella, mumps, diphtheria, pertussis, tetanus, and hepatitis B. The study showed the percentage of children with positive IgG values for vaccine-preventable infections. The highest percentage of children had protective antibody levels to measles (84.2% in children with nephrotic syndrome and 92.6% in those with inflammatory bowel disease) and rubella (71% and 80.4%, respectively). The lowest percentage of children with protective antibodies was for hepatitis B (5.2% and 29.2% respectively). Antibodies to mumps, diphtheria, pertussis, and tetanus were found not in all children (from 39,4% to 82,9%). The remaining percentage of children did not have detectable IgG antibodies to vaccine-preventable infections. Not all children, despite the previous vaccination, preserved antibodies to vaccine-controlled infections and remained unprotected by specific IgG antibodies. The issue of a booster vaccine dose should be considered in children without contraindications to vaccination. Children receiving long-term immunosuppressive therapy require an individual vaccination approach, including a specific definition of the performed vaccination.

Keywords: immunosuppressive therapy, inflammatory bowel diseases, nephrotic syndrome, post-vaccination immunity, specific antibodies, vaccine-preventable infections.

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

Procedia PDF Downloads 82

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Eman Abdullah Morsi, Hend Okasha, Heba Abdel Hady, Mortada El-Sayed, Mohamed Abbas Shemis

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Context: Linum usitatissimum (Linn), known as Flaxseed, is one of the most important medicinal plants traditionally used for various health as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents as well as evaluate the antioxidant using α, α-diphenyl-β-picrylhydrazyl (DPPH), 2-2'azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and total antioxidant capacity (TAC) assay and investigation of anti-inflammatory by Bovine serum albumin (BSA) and anticancer activities of hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7) have been applied on hexane, ethyl acetate, n-butanol and methanol extracts and also, fractions of methonal extract (hexane, ethyl acetate and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts and fractions of methanolic extract were tested on (HepG2) and (MCF7). Results: Methanolic extract and its ethyl acetate fraction contain higher contents of total phenols and flavonoids. In addition, methanolic extract had higher antioxidant activity. Butanolic and ethyl acetate fractions yielded higher percent of inhibition of protein denaturation. Meanwhile, ethyl acetate fraction and methanolic extract had anticancer activity against HepG2 and MCF7 (IC50=60 ± 0.24 and 29.4 ± 0.12µg.mL⁻¹) and (IC50=94.7 ± 0.21 and 227 ± 0.48µg.mL⁻¹), respectively. In Gas chromatography-mass spectrometry (GC-MS) analysis, methanolic extract has 32 compounds, whereas; ethyl acetate and butanol fractions contain 40 and 36 compounds, respectively. Conclusion: Flaxseed contains totally different biologically active compounds that have been found to possess good variable activities, which can protect human body against several diseases.

Keywords: phenolic content, flavonoid content, HepG2, MCF7, hemolysis-assay, flaxseed

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Leyla Sattarzadeh, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6) and adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of resistance exercise training on these inflammatory markers, the present study aimed to examine the effect of eight week different patterns of resistance exercise training on CRP, IL-6 and ICAM-1 levels in healthy untrained women. 40 volunteered and healthy untrained female university students (aged: 21+ 3 yr., Body Mass Index: 21.5+ 3.5 kg/m2) were selected purposefully and divided into three groups. At the end of training protocol and after subjects drop during the protocol in upper body exercise training (n=11), lower body (n=12) completed the eight week of training period although the control group (n=7) did anything. Blood samples gathered pre and post experimental period and CRP, IL-6 and ICAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one way Analysis of Variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP and ICAM-1 showed no significant changes due to the exercise training. But there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper and lower body exercise training by involving the different amount of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP and ICAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: C-reactive protein, interleukin-6, intracellular adhesion molecule-1, resistance training

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Authors: Mukesh Saran, Ashima Bagaria

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Green nanotechnology is the most researched field in the current scenario. Herein we study the synthesis of Zinc and Ferrous nanoparticles using Moringa oleifera leaf extracts. Our protocol using established protocols heat treatment of plant extracts along with the solution of copper sulphate in the ratio of 1:1. The leaf extracts of Moringa oleifera were prepared in deionized water. Copper sulfate solution (1mM) was added to this, and the change in color of the solution was observed indicating the formation of Cu nanoparticles. The as biosynthesized Cu nanoparticles were characterized with the help of Scanning Electron Microscopy (SEM), and Fourier Transforms Infrared Spectroscopy (FTIR). It was observed that the leaf extracts of Moringa oleifera can reduce copper ions into copper nanoparticles within 8 to 10 min of reaction time. The method thus can be used for rapid and eco-friendly biosynthesis of stable copper nanoparticles. Further, we checked their antimicrobial and antioxidant potential, and it was observed that maximum antioxidant activity was observed for the particles prepared using the heating method. The maximum antibacterial activity was observed in Streptomyces grisveus particles and in Triochoderma Reesei for the maximum antifungal activity. At present, we are engaged in studying the anti-inflammatory activities of these as prepared nanoparticles.

Keywords: green synthesis, antibacterial, antioxidant, antifungal, anti-inflammatory

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