Search results for: Airway inflammation

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: A. B. Amna, M. A. E. Samia, A. K. Hassan

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The clinical, pathological, hematological and biological changes in Newzealand rabbits groups given daily oral doses of 0.1,0.25 and 0.5 ml/kg body weight/day of Cpmbopogon proximus oil extract were investigated in an experiment durated for 21 days. Other than the dose co-related mortality rates, the clinical signs were observed daily after dosing to be low appetite and nervous signs including restlessness and increased consciousness. Pulmonary excretion of the oil extract led to bloody spots on the lungs, lymphocyte infiltration, congestion and edema. Renal glumeruli manifested lymphocyte infiltration in addition to shrinkages and easinophilic material in the medulla, if considered with the corticomedullary generalized necrosis and the significant changes in urea, they can explain the renal dysfunction. Hepatic malfunction was manifested by significant changes in serum alkaline phosphatase and aspartate transferases accompanied by the congested, fatty changed livers. The direct physical effect of the extracted oil was detected by the catarrhal inflammation of the intestines.There was no significant haematological change except for the slight changes in RBCs and MCVs in rabbits given the highest dose. Future work for Cpmbopogon proximus oil extract was forwarded and practical implications of the result were highlighted.

Keywords: toxicity, cymbopogon proximus (maharaib), oil extract, Newzealand rabbits

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Authors: U. N. Vokhidov, U. S. Khasanov, A. A. Ismailova

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Background: Currently, the researches on the development of chronic polypoid rhinosinusitis cytokines play a major role. The aim of this study was the comparison of indicators IL-2, IL-4, IL-8 in the peripheral blood and nasal secretions of patients with various forms of chronic polypoid rhinosinusitis. Material and methods: We studied 50 patients with chronic polypoid rhinosinusitis receiving hospital treatment in the ENT department of the 3-rd clinic of Tashkent Medical Academy. It was carried out a comprehensive study including morphological examination, immunological study of blood and nasal secretions on the IL-2, IL-4 and IL-8. Results: The results of immunological studies of peripheral blood showed that patients with ‘eosinophilic’ polyps were increased IL-2 and IL-4 in patients with ‘neutrophils’ polyps were increased IL-2 and IL-8. Immunological investigation nasal secretions taken from patients with nasal polyposis rhinosinusitis showed that patients with ‘eosinophilic’ polyps also increased IL- 2 and IL- 4 in patients with ‘neutrophils’ polyps - increased IL-2 and IL-8. Conclusion: In patients with ‘eosinophilic’ polyps revealed the presence of immunity to the allergy of the body, patients with ‘neutrophilic’ polyps identified immunity to the presence of inflammation, it is necessary to take into account the doctor-otolaryngologist when choosing a treatment strategy for the prevention of recurrence of the disease.

Keywords: chronic polypoid rhinosinusitis, immunology, cytikines, nasal secretion

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Hamida Memon

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Rheumatoid arthritis (RA) is a persistent inflammation of the joints caused by an aggressive immune reaction leading to pain, stiffness, and limited function. Abatacept, a selective co-modulator, is a promising option for treatment and may have better safety profiles compared to other interventions. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept.

Keywords: Rheumatoid arthritis, abatacept, control group, bone disease

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Authors: Maryam Bahreini, Mostafa Talebi Garekani, Fatemeh Rasooli, Atefeh Abdollahi

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Introduction: Procedural sedation and analgesia have been desirable to handle painful procedures. The trend to find the agent with more efficacy and less complications is still controversial; thus, many sedative regimens have been studied. This study tried to assess the effectiveness and adverse effects of thiopental sodium-fentanyl with the known medication, ketamine-propofol for procedural sedation in the emergency department. Methods: Consenting patients were enrolled in this randomized double-blind trial to receive either 1:1 ketamine-propofol (KP) or thiopental-fentanyl (TF) 1:1 mg: Mg proportion on a weight-based dosing basis to reach the sedation level of American Society of Anesthesiologist class III/IV. The respiratory and hemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared. The study was registered in Iranian randomized Control Trial Registry (Code: IRCT2015111325025N1). Results: 96 adult patients were included and randomized, 47 in the KP group and 49 in the TF group. 2.1% in the KP group and 8.1 % in the TF group experienced transient hypoxia leading to performing 4.2 % versus 8.1 % airway maneuvers for 2 groups, respectively; however, no statistically significant difference was observed between 2 combinations, and there was no report of endotracheal placement or further admission. Patient and physician satisfaction were significantly higher in the KP group. There was no difference in respiratory, gastrointestinal, cardiovascular and psychiatric adverse events, recovery time and patient recall of the procedure between groups. The efficacy and complications were not related to the type of procedure or patients’ smoking or addiction trends. Conclusion: Ketamine-propofol and thiopental-fentanyl combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. It is estimated that thiopental fentanyl combination can be as potent and efficacious as ketofol with relatively similar incidence of adverse events in procedural sedation.

Keywords: adverse effects, conscious sedation, fentanyl, propofol, ketamine, safety, thiopental

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Authors: Sophie N. Selby-Pham, Yudie Wang, Louise Bennett

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Consumption of grapes promotes health and reduces the risk of chronic diseases due to the action of grape phytochemicals in regulation of Oxidative Stress and Inflammation (OSI). The bioefficacy of phytochemicals depends on their absorption in the human body. The time required for phytochemicals to achieve maximal plasma concentration (Tₘₐₓ) after oral intake reflects the time window of maximal bioefficacy of phytochemicals, with Tₘₐₓ dependent on physicochemical properties of phytochemicals. This research collated physicochemical properties of grape phytochemicals from white and red grapes to predict their Tₘₐₓ using pharmacokinetic modelling. The predicted values of Tₘₐₓ were then compared to the measured Tₘₐₓ collected from clinical studies to determine the accuracy of prediction. In both liquid and solid intake forms, white grapes exhibit a shorter Tₘₐₓ range (0.5-2.5 h) versus red grapes (1.5-5h). The prediction accuracy of Tₘₐₓ for grape phytochemicals was 33.3% total error of prediction compared to the mean, indicating high prediction accuracy. Pharmacokinetic modelling allows prediction of Tₘₐₓ without costly clinical trials, informing dosing frequency for sustained presence of phytochemicals in the body to optimize the health benefits of phytochemicals.

Keywords: absorption kinetics, phytochemical, phytochemical absorption prediction model, Vitis vinifera

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Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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Authors: Fardis Teifoori, Mehdi Dehghani, Idoia Postigo, Jorge Martinez

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Introduction: Many skin disorders, such as atopic dermatitis (AD), is characterized by inflammation, infection, and hyperplasia. In this work, keratinocytes from AD patients are used to study the pomegranate seed oil properties for skin care. Material and methods: Isolated keratinocytes from patients with AD were cultured and stimulated by IL-9 (20 ng/ml) and TNF-α (50ng/ml) for 48h to induce vascular endothelial growth factor (VEGF) and Regulated upon activation, normal T cell expressed and secreted (RANTES) production, respectively, in the presence of different concentrations of pomegranate seed oil (20, 50, 100, and 200 µM). Finally, the concentrations of RANTES and VEGF in the cell culture supernatant were quantified according to the standard protocol of commercial ELISA kits. Results: The results indicated that pomegranate seed oil concentrations of 50, 100, and 200 µM could significantly inhibit the production of VEGF and RANTES by stimulating keratinocytes with IL-9 (20 ng/ml) and TNF-α (50ng/ml), respectively. The decrease in VEGF and RANTES concentration in the presence of the pomegranate seed oil concentrations of 20 and 50 uM was not significant. Conclusion: It was concluded that pomegranate seed oil (PSO) counteracts atopic dermatitis conditions dose-dependently: with the highest effect at the concentration of 200 µM. We suggest that the inexpensive and easily available pomegranate seed oil is a good candidate for cosmetics and clinical utilization for skin care.

Keywords: atopic dermatitis, pomegranate, Punica granatum, RANTES, VEGF

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Authors: Anat Achiron

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Background: Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system in young adults. It involves the immune system attacking the protective covering of nerve fibers (myelin), leading to inflammation and damage. MS can result in various neurological symptoms, such as muscle weakness, coordination problems, and sensory disturbances. Seizures are not common in MS, and the frequency is estimated between 0.4 to 6.4% over the disease course. Objective: Investigate the frequency of seizures in individuals with multiple sclerosis and to identify associated risk factors. Methods: We evaluated the frequency of seizures in a large cohort of 5686 MS patients followed at the Sheba Multiple Sclerosis Center and studied associated risk factors and comorbidities. Our research was based on data collection using a cohort study design. We applied logistic regression analysis to assess the strength of associations. Results: We found that younger age at onset, longer disease duration, and prolonged time to immunomodulatory treatment initiation were associated with increased risk for seizures. Conclusions: Our findings suggest that seizures in people with MS are directly related to the demyelination process and not associated with other factors like medication side effects or comorbid conditions. Therefore, initiating immunomodulatory treatment early in the disease course could reduce not only disease activity but also decrease seizure risk.

Keywords: epilepsy, seizures, multiple sclerosis, white matter, age

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Authors: Santosh Tummidi, Pragati Sathe, Kanchan Kothari, Prachi Gholap, Mona Agnihotri, Gwendolyn Fernandes, Leena Naik, Rachana Chaturvedi

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Introduction: EUS-Guided Fine Needle Aspiration/Brush (EUS-FNA/Brush) has become increasingly popular for the diagnosis and staging of gastrointestinal and peri-gastrointestinal lesions. Objective: To evaluate the diagnostic accuracy and spectrum of lesions in gastrointestinal EUS-FNA. Material and Methods: A total of 124 EUS-FNA during the period from Aug 2015-Nov 2016 were studied. Results: Age ranged from 13-80 years with a slight female predominance. CBD was the most common site with 47 cases amongst which were 9 adenocarcinoma, and 7 cases were suspicious for malignancy. Pancreatic EUS-FNA showed 5 adenocarcinoma, 2 SPEN, 1 case each of neuroendocrine tumor, anaplastic carcinoma and NHL. Amongst oesophageal lesions, 3 cases were suspicious for malignancy, and 4 were inflammatory, 4 showed SCC, 1case each adenocarcinoma and leiomyoma. Stomach- 1 case each of adenocarcinoma, granulomatous inflammation, and GIST. Periportal lymph nodes were the commonest nodes, and there were 11 necrotising granulomatous inflammations, 3 metastatic adenocarcinoma, 2 cases of atypical cells and 1 case of NHL. 17 cases were unsatisfactory, 41 cases had histopathology follow up with 85% cases being concordant. Conclusion: EUS-FNA is reliable, sensitive and specific. It can be utilized for better management of intra-abdominal lesions.

Keywords: EUS-FNA, brush, cytology, histopathology

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Authors: Eun Young Choi, So Hui Choe, Jin Yi Hyeon, Ji Young Jin, Bo Ram Keum, Jong Min Lim, Hyung Rae Cho, Kwang Keun Cho, In Soon Choi

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This research analyzed the effect of β-glucan that is expected to alleviate the production of inflammatory mediator in macrophagocyte, which was processed by the lipopolysaccharide (LPS) of Escherichia, a pathogen related to allergy. The incubated layer was used for nitric oxide (NO) analysis. The DNA-binding activation of the small unit of NF-κB was measured using ELISA-based kit. In RAW264.7 cells that were vitalized by E.coli LPS, β-glucan inhibited both the combatant and rendering phases of inducible NO synthase (iNOS)-derived NO. β-glucan increased the expression of heme oxygenase-1 (HO-1) in the cell that was stimulated by E.coli LPS, and HO-1 activation was inhibited by SnPP. This shows that NO production induced by LPS is related to the inhibition effect of β-glucan. The phosphorylation of JNK and p38 induced by LPS were not influenced by β-glucan, and IκB-α decomposition was not influenced either. Instead, β-glucan remarkably inhibited the phosphorylation of STAT1 that was induced by E.coli LPS. Overall, β-glucan inhibited the production of NO in macrophagocyte that was vitalized by E.coli LPS through HO-1 induction and STAT1 pathways inhibition in this research. As the host inflammation reaction control by β-glucan weakens the progress of allergy, β-glucan can be used as an effective treatment method.

Keywords: β-glucan, lipopolysaccharide (LPS), nitric oxide (NO), RAW264.7 cells, STAT1

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Authors: Feng Ju Chuang, Yu Wen Wang, Tai Jung Hsieh, Shyh Ming Kuo

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Polylactic acid is a synthetic polymer with good biocompatibility and degradability, is widely used in clinical applications. In this study, we utilized Polylactic acid particles as stimulants for macrophages and the collagen synthesis of co-cultured fibroblasts was evaluated. The results indicated that Polylactic acid particles were nontoxic to cells from 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. No obvious inflammation effect was observed (under the PLLA concentration of 1 mg/mL) after 24-h co-culture of Raw264.7 and NIH3T3 cells (from TNF-α assay). The addition of PLLA particles to the Raw264.7 and NIH3T3 co-cultures increased the synthesis of collagen, the highest collagen synthesis from the fibroblast was the 0.2 mg/mL (approximately 60% increased as compared with without addition Polylactic acid particles). Moreover, a co-axial atomization delivery device was used to percutaneously introduce Polylactic acid particles into the dermis layer and stimulating macrophages to secrete growth factors promoting fibroblasts to produce collagen. The preliminary results demonstrated the synthesis of collagen was increased mildly after the introduction of Polylactic acid particles for 28-d post implantation. The Polylactic acid particles could be successfully introduced into the dermis layer from H&E staining examination, however, the optimum concentration of Polylactic acid particles and the time-period for collagen synthesis still need to be evaluated.

Keywords: collagen synthesis, macrophage, NIH3T3 cells, polylactic acid particles

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Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

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K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

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Authors: Urarat Nanna, Jarinyaporn Naowaboot

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Tiliacora triandra (T. triandra) is traditional Southeast Asian medicine and widely used in the cuisines of northeast Thailand and Laos. It has been used as antipyretic, detoxication agent, antiinflammation. But the activity of T. triandra leaf water extract (TTW) in the regulation of metabolic syndrome is still little known. In this study, we evaluated the effects of TTW in high-fat diet (HFD)-induced obese mice. Male ICR mice were induced to be obese by HFD feeding (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with TTW at 250 and 500 mg/kg/day. The biochemical parameters and histology analysis were measured at the end of treatment period. After 6 weeks of TTW treatment, the hyperglycemia, hyperinsulinemia, hyperleptinemia and hyperlipidemia were significantly decreased. Hepatic lipid accumulation and adipocyte hypertrophy were also reduced. Serum adiponectin was increased in TTW-treated obese mice. TTW treatment could reduce the malondialdehyde in serum and liver tissue. Furthermore, the elevated serum inflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 were reduced (MCP-1) by TTW. These results suggest that T. triandra leaf is a beneficial plant in alleviating hyperglycemia, hyperlipidemia, oxidative stress and inflammation in the obese condition induced by HFD.

Keywords: Tiliacora triandra, insulin resistance, hyperlipidemia, oxidative stress

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Ali Olfati, Parichehr Nouri

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Objective: In this study, we have investigated for the first time in the literature the efficacy of riboflavin [VB2] in preventing uterus As₂O₃ damage. Methods: Rats received 40 μg LHRHa for estrus synchronization. 48 pregnant Wistar rats were included. Four groups were formed with 7 rats in each group: Sham, 1.5 mg arsenic trioxide (As₂O₃/L) alone or in combination with VB2 [20 and 40 mg/L] in drinking water [for 21 days continuously]. Similar to maternal generation treatment, the F1-female generation was also arranged [for 35 days continuously until puberty]. Results: Data indicated that As₂O₃ reduced body weight and feed intake (p<0.05). Furthermore, the serum malondialdehyde levels in the As₂O₃ group were significantly higher than that of the control group (p<0.05). At the same time, total antioxidative status and the activities of glutathione peroxidase, superoxide dismutase, and catalase were reduced (p<0.05). Meanwhile, As₂O₃ remarkably increased the production of inflammatory markers [interleukin 6 and C-reactive protein](p<0.05). As₂O₃ administration induced uterus apoptosis-related genes by upregulating caspase-3, iNOS, and Bax genes and downregulating Bcl-2 gene of pubertal F1-female rats (p<0.05). Conclusion: Our observation indicated that VB2 therapy is potentially an effective strategy to modifying the detrimental effects of As₂O₃ in pubertal F1-female rats via suppresses oxidative damages.

Keywords: As₂O₃, inflammation, puberty, vitamin B2

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Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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Authors: Farah Nameni, Hamidreza Poursadra, Maasumeh Nurani Pilehrud

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Exercise training induced Inflammation and stress. Antioxidant, for example L- Carnitine has beneficial effects in immune system and increased antioxidant enzymes activity. L- Carnitine protects the tissue against the oxidative side effect and helps the body to protect against stress during and after acute exercise. The aim of this study was to determine the effect of L-Carnitine on the blood enzymes: GPX SOD, CAT and GR response. In this study, 20 basketball players girls participated. Subjects were randomly assigned into two groups; placebo and supplementation. Antioxidadision enzymes (Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase) evaluated. L-Carnitine supplement group orally daily received 3000 mg powder for 14 dys. Then all participates trained basketball exercise acute. Blood samples were drawn vein before and immediately after exercise. Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase were measured, and data was analyzed using repeated measure ANOVA, Bonferroni and t-test. Our results showed: SOD, GPX and GPX (P < 0.05) have a significant increase. These results suggest L-Carnitine supplementation may increase GPX SOD, CAT, and basal anti oxidative capacity. L-Carnitine can modulate the alterations of exercise oxidative damage in girl basketball players.

Keywords: l-carnitine, GPX, SOD, CAT, exercise, GR, anti-oxidant

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Authors: Salim Cerig, Fatime Geyikoglu, Pınar Akpulat, Suat Colak, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Kubra Koc

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This study was designed to evaluate whether carvacrol (CAR) could provide protection against lung injury by acute pancreatitis development. The rats were randomized into groups to receive (I) no therapy; (II) 50 μg/kg cerulein at 1h intervals by four intraperitoneal injections (i.p.); (III) 50, 100 and 200 mg/kg CAR by one i.p.; and (IV) cerulein+CAR after 2h of cerulein injection. 12h later, serum samples were obtained to assess pancreatic function the lipase and amylase values. The animals were euthanized and lung samples were excised. The specimens were stained with hematoxylin-eosin (H&E), periodic acid–Schif (PAS), Mallory's trichrome and amyloid. Additionally, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The results showed that the serum activity of lipase and amylase in AP rats were significantly reduced after the therapy (p<0.05). We also found that the 100 mg/kg dose of CAR significantly decreased 8-OH-dG levels. Moreover, the severe pathological findings in the lung such as necrosis, inflammation, congestion, fibrosis, and thickened alveolar septum were attenuated in the AP+CAR groups when compared with AP group. Finally, the magnitude of the protective effect on lung is certain, and CAR is an effective therapy for lung injury caused by AP.

Keywords: antioxidant activity, acute pancreatitis, carvacrol, experimental, lung injury, oxidative DNA damage

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Authors: Bilal Ahmad

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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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Authors: Ankush Kalra, Mirza Masroor, Usha Manaktala, B. C. Koner, T. K. Mishra

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Introduction: Pre-eclampsia affects 3-5% of pregnancies worldwide and increases maternal-fetal morbidity and mortality. Reduced placental perfusion induces the release of biomolecules by the placenta into maternal circulation causing endothelial dysfunction. Zinc dependent matrix metalloproteinase-2 (MMP-2) may be up-regulated and interact with circulating factors of oxidative stress and inflammation to produce endothelial dysfunction in pre-eclampsia. Aim: To study the functional genetic polymorphism of MMP-2 gene (g-1306 C>T) in pre-eclampsia and its effect on serum MMP-2 levels in these patients. Method: Hundred pre-eclampsia patients and hundred age and gestation period matched healthy pregnant women with their consent were recruited in the study. Serum MMP-2 levels in all subjects were estimated using standard ELISA kits. MMP-2 gene (g.- 1306 C>T) SNPs were genotyped using whole blood by ASO-PCR. Result: The pre-eclampsia patients had higher serum levels of MMP-2 compared to the healthy pregnant (p < 0.05). Also the MMP-2 genotype was associated with significant alteration in the serum MMP-2 concentration in these patients (p < 0.05). Conclusion: This study results suggest an association of MMP-2 genetic polymorphism and serum levels of MMP-2 to the path physiology of hypertensive disorder of pregnancy.

Keywords: allele specific oligonucleotide polymerase chain reaction (ASO-PCR), enzyme linked immunosorbent assay (ELISA), matrix metalloproteinase-2 (MMP-2), pre-eclampsia

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Authors: Nevila Alliu, Saimir Heta, Ilma Robo, Vera Ostreni

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Periodontitis as an oral pathology caused by specific bacterial flora functions as a focal infection for the onset and aggravation of arteriosclerosis. These two distant pathologies, since they affect organs at a distance from each other, communicate with each other with correlation at the level of markers of inflammation in the blood. Fluctuations in the level of fibrinogen in the blood, depending on the active or passive phase of the existing periodontitis, affect the promotion of arteriosclerosis. The study is of the review type to analyze the effect of non-surgical periodontal treatment on fluctuations in the level of fibrinogen in the blood. The reduction of fibrinogen levels in the blood after non-surgical periodontal treatment of periodontitis in the patient's cavity is visible data and supported by literature sources. Also, the influence of a high amount of fibrinogen in the blood on the occurrence of arteriosclerosis is also another important data that again relies on many sources of literature. Conclusions: Thromboembolism and arteriosclerosis, as risk factors expressed in clinical data, have temporary bacteremia in the blood, which can occur significantly and often between phases of non-surgical periodontal treatment of periodontitis, treatments performed with treatment phases and protocols of predetermined treatment. Arterial thromboembolism has a significant factor, such as high levels of fibrinogen in the blood, which are significantly reduced during the period of non-surgical periodontal treatment.

Keywords: fibrinogen, refractory periodontitis, atherosclerosis, non-surgical, periodontal treatment

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Authors: Lourdes Hanna, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan, Grace Imaguezegie

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Background: Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments. Main body: Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neu-ronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not the same finding. Conclusion: Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.

Keywords: intervention, central nervous system, neurodegeneration, neuroinflammation

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Suparmi, Israhnanto Isradji, Dina Fatmawati, Iwang Yusuf

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Kepel (Stelechocarpus burahol) is one of the traditional plants originating from Indonesia that can be used to prevent pregnancy, launched urine and kidney inflammation. Kepel pulp has compounds alkaloid, triterpenoid, tannin, saponin, and flavonoid, when used will give the hormonal and cytotoxic effect. This study was aimed at evaluating ethanol extract of kepel in vivo for anti-implantation activities. In this experimental study with post test only control group design, 20 female mice were randomly divided into 4 groups. It was divided into the control, the 0,65 mg dose, 1,3 mg dose, and 3,6 mg dose of kepel pulp extract group. The extract soluted in DMSO’s solution and was given 1 ml per mice. The extract was given 10 days before copulation until 18 days of pregnancy. Then, the number of implantation, presence of fetus, and embrio resorbtion were recorded and used to calculate the percentage anti-implantation effect. The results were tested by One-way ANOVA. The mean number of implantation in group control, 0,65 mg;1,3 mg; and 2,6 mg were 5,60±1,14; 6,20± 1,64; 7,60±1,51; 8,00± 1,58, respectively. One way Annova test showed that there is no significant difference in the number of implantation between the group (p > 0,05). The administration of kepel pulp ethanol extract had no effect on the percentage anti-implantation effect and the number of and embrio resorbtion.

Keywords: antiimplantation, fetus, Stelechocarpus burahol, flavonoid

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Authors: Sadia Munir

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Preeclampsia is the contributor to the worldwide maternal mortality of approximately 100,000 deaths a year. It complicates about 10% of all pregnancies and is the first cause of maternal admission to intensive care units. Predicting preeclampsia is a major challenge in obstetrics. More importantly, no major progress has been achieved in the treatment of preeclampsia. As placenta is the main cause of the disease, the only way to treat the disease is to extract placental and deliver the baby. In developed countries, the cost of an average case of preeclampsia is estimated at £9000. Interestingly, preeclampsia may have an impact on the health of mother or infant, beyond the pregnancy. We performed a systematic search of PubMed including the combination of terms such as preeclampsia, biomarkers, treatment, hypoxia, inflammation, oxidative stress, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, microRNAs. In this review, we have summarized current knowledge on the identification of potential biomarkers for the diagnosis of preeclampsia. Although these studies show promising data in early diagnosis of preeclampsia, the current value of these factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Keywords: activin, biomarkers, growth factors, miroRNA

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Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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Authors: Komal Khan, Hafsa Zaneb, Saima Masood, Muhammad Younus, Sanan Raza

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Cigarette smoke induces many physiological and pathological changes in respiratory tract like goblet cell hyperplasia and regional distention of airspaces. It is also associated with elevation of inflammatory profiles in different airway compartments. As probiotics are generally known to promote mucosal tolerance, it was postulated that prophylactic use of probiotics can be helpful in reduction of respiratory damage induced by cigarette smoke exposure. Twenty-four adult mice were randomly divided into three groups (cigarette-smoke (CS) group, cigarette-smoke+ Lactobacillus (CS+ P) group, control (Cn) group), each having 8 mice. They were exposed to cigarette smoke for 28 days (6 cigarettes/ day for 6 days/week). Wright-Giemsa staining of bronchoalveolar lavage fluid (BALF) was performed in three mice per group. Tissue samples of trachea and lungs of 7 mice from each group were processed by paraffin embedding technique for haematoxylin & eosin (H & E) and alcian blue- periodic acid-Schiff (AB-PAS) staining. Then trachea (goblet cell number, ratio and loss of cilia) and lungs (airspace distention) were studied. The results showed that the number of goblet cells was increased in CS group as a result of defensive mechanism of the respiratory system against irritating substances. This study also revealed that the cells of CS group having acidic glycoprotein were found to be higher in quantity as compared to those containing neutral glycoprotein. However, CS + P group showed a decrease in goblet cell index due to enhanced immunity by prophylactically used probiotics. Moreover, H & E stained tracheas showed significant loss of cilia in CS group due to propelling of mucous but little loss in CS + P group because of having good protective tracheal epithelium. In lungs, protection of airspaces was also much more evident in CS+ P group as compared to CS group having distended airspaces, especially at 150um distance from terminal bronchiole. In addition, a comprehensive analysis of inflammatory cells population of BALF showed neutrophilia and eosinophilia was significantly reduced in CS+ P group. This study proved that probiotics are found to be useful for reduction of changes in micro-architecture of the respiratory system. Thus, dietary supplementation of probiotic as prophylactic measure can be useful in achieving immunomodulatory effects.

Keywords: cigarette smoke, probiotics, goblet cells, airspace enlargement, BALF

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