Search results for: inflammatory factors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 10980

Search results for: inflammatory factors

10860 John Cunningham Virus Interaction with Multiple Sclerosis Disease Progression

Authors: Sina Mahdavi

Abstract:

Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.

Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity

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10859 Novel Molecular Mechanisms Involved in Macrophage Phenotypic Polarization

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

Abstract:

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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10858 The Effect of Aerobic Training Program on Some Pro-Inflammatory Cytokine in Smokers

Authors: Laleh Behboudi Tabrizi, Melika Naserzare

Abstract:

Accumulating experimental and epidemiologic data smoker individuals are more prone to systemic inflammation than non-smokers. In this study we aimed to determine serum TNF-α and C-reactive protein (CRP) as pro-inflammatory cytokines in response to 3 months aerobic training in smoker men. A total 30 middle-aged healthy smokers selected for participate in this study and were divided into either control or exercise groups. The subjects in exercise group were completed a 3 months aerobic training program for 3 sessions per week at 60 – 80 % of maximal heart rate. Those in control group did nit participated in exercise training. Pre and post-training of CRP and TNF-α were measured in two groups. Student’s t-tests for paired samples were performed to determine whether there were signigcant within-group changes in the outcomes. P value of <0.05 was accepted as significant. No significant differences were found in anthropometrical and biochemical markers between two groups at baseline. Aerobic training program resulted in a significant decrease in anthropometrical markers and serum TNF-α but not in serum CRP in exercise group. All variables remained without changes in control groups. Based on these finding, it is concluded that aerobic training can be improve inflammatory cytokine with emphasis on TNF-α in smokers.

Keywords: cigarette, cytokine, chronic training, inflammation

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10857 Impact of Transgenic Adipose Derived Stem Cells in the Healing of Spinal Cord Injury of Dogs

Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

Abstract:

The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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10856 Fluoride-Induced Stress and Its Association with Bone Developmental Pathway in Osteosarcoma Cells

Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

Abstract:

Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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10855 Prediction and Identification of a Permissive Epitope Insertion Site for St Toxoid in cfaB from Enterotoxigenic Escherichia coli

Authors: N. Zeinalzadeh, Mahdi Sadeghi

Abstract:

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of non-inflammatory diarrhea in the developing countries, resulting in approximately 20% of all diarrheal episodes in children in these areas. ST is one of the most important virulence factors and CFA/I is one of the frequent colonization factors that help to process of ETEC infection. ST and CfaB (CFA/I subunit) are among vaccine candidates against ETEC. So, ST because of its small size is not a good immunogenic in the natural form. However to increase its immunogenic potential, here we explored candidate positions for ST insertion in CfaB sequence. After bioinformatics analysis, one of the candidate positions was selected and the chimeric gene (cfaB*st) sequence was synthesized and expressed in E. coli BL21 (DE3). The chimeric recombinant protein was purified with Ni-NTA columns and characterized with western blot analysis. The residue 74-75 of CfaB sequence could be a good candidate position for ST and other epitopes insertion.

Keywords: bioinformatics, CFA/I, enterotoxigenic E. coli, ST toxoid

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10854 Association Analysis of Putative Loci with Coronary Artery Disease

Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

Abstract:

Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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10853 Role of Inflammatory Markers in Arthritic Rats Treated with Ethanolic Bark Extract of Albizia procera

Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

Abstract:

Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

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10852 Suppression of DMBA/TPA-Induced Skin Tumorigenesis by Menthol through Inhibition of Inflammation, NF-kappaB, Ras-Raf-ERK Pathway

Authors: Zhaoguo Liu, Cunsi Shen, Yin Lu

Abstract:

Growing evidence has shown that menthol has potent anticancer activity in various human cancers. However, its effect on skin cancer remains largely unknown. In the present study, we investigated the chemopreventive potential of menthol against 7, 12-dimethylbenz[a] anthracene(DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in ICR mice. Our results showed that menthol significantly inhibited TPA-induced inflammatory responses and pro-inflammatory cytokine release. We also found that menthol treatment significantly inhibited TPA-induced lipid peroxidation (LPO), mouse UDP-glucumno-syltransferase (UGT), mouse NADH Dehydrogenase, Quinone 1 (NQO1) release. Furthermore, we found menthol treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001). Interestingly, we observed that menthol treatment significantly inhibited TPA-induced altered activity of NF-κB in skin tumor. Consistently, menthol-treated tumors also showed significantly suppressed the Ras-Raf-ERK signaling pathway. Thus, our results suggest that menthol inhibits DMBA/TPA-induced skin tumorigenesis by attenuating the Ras and inhibiting NF-κB activity via inhibition of inflammation responses and pro-inflammatory cytokine release.

Keywords: DMBA/TPA, NF-κB, Ras-Raf-ERK, skin tumorigenesis

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10851 Bioactive Potentials of Peptides and Lipids from Green Mussel (Perna viridis), Horse Mussel (Modiolus philippinarum) and Charru Mussel (Mytella charruana)

Authors: Sharon N. Nuñal, May Flor S. Muegue, Nizzy Hope N. Cartago, Raymund B. Parcon, Sheina B. Logronio

Abstract:

The antioxidant and anti-inflammatory potentials of Perna Viridis, Modiolus philippinarum, and Mytella charruana found in the Philippines were assessed. Mussel protein samples were hydrolyzed using trypsin, maturase, alcalase and pepsin at 1% and 2% concentrations and then fractionated through membrane filtration (<10 kDa and <30 kDa). Antioxidant assays showed that pepsin hydrolysate at 2% enzyme concentration exhibited the maximum activities for both 2,2-Diphenyl-1-picrylhydrazyl (DPPH) Radical Scavenging Activity (155-176 µM TE/mg protein) and 2,2-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging (67-68 µM TE/mg protein) assays while trypsin hydrolysate dominated the Ferric Reducing Antioxidant Power (FRAP) for the three mussel species. Lower molecular weight peptide fractions at <10 kDa exhibited better antioxidant activities than the higher molecular weight fractions. The anti-inflammatory activities of M. philippinarum and M. charruana showed comparable protein denaturation inhibition potentials with the highest in P. Viridis samples (98.93%). The 5-Lipoxygenase (5-LOX) inhibitory activities of mussel samples showed no significant difference with inhibition exceeding 70%. P. Viridis demonstrated the highest inhibition against Cyclooxygenase-2 (COX-2) at 56.19%, while the rest showed comparable activities. This study showed that the three mussel species are potential sources of bioactive peptides and lipids with antioxidant and anti-inflammatory properties.

Keywords: anti-inflammatory, antioxidant, bioactive properties, mussel

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10850 Shielding Engineered Islets with Mesenchymal Stem Cells Enhance Survival under Hypoxia by Inhibiting p38 MAPK

Authors: Bhawna Chandravanshi, Ramesh Bhonde

Abstract:

In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

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10849 Regulation of PKA-Dependent Calcineurin as a Switch in Cell Secretion

Authors: Hani M. M. Alothaid, Louise Robson, Richmond Muimo

Abstract:

This study will investigate cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) dependent calcineurin (Cn), known as protein phosphatase 2 B (PP2B) as well, regulation of chloride ion (Cl⁻) secretion and the release of pro-inflammatory molecules in immune cells such as cytokines. THP-1-derived monocytes, primary human monocytes and the bronchial epithelial cell line (16HBE14o-) were used in this study. The 16HBE14o- cells were chosen as positive control. Hence, to further confirm the expression of cystic fibrosis transmembrane conductance regulator (CFTR), calcium binding protein (S100A10), annexin A2 (AnxA2) and calcineurin A subunit (CnA) in all three cell types, cell lysate was probed against corresponding primary antibodies by immunoblotting. Western blot analyses show the expression of CFTR, AnxA2, CnA and S100A10 in THP-1-derived monocytes and primary human monocytes. In conclusion, CFTR, S100A10, CnA and AnxA2 are expressed in THP-1-derived monocytes and primary human monocytes and regulate Cl⁻ secretion. Also, they may play a role in the pro-inflammatory molecules release. The ongoing work will confirm interaction between these proteins in the cell lines.

Keywords: annexin A2, calcineurin, CFTR, chloride, monocytes, pro-inflammatory molecules, S100A10

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10848 Effects on Inflammatory Biomarkers and Respiratory Mechanics in Laparoscopic Bariatric Surgery: Desflurane vs. Total Intravenous Anaesthesia with Propofol

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

Abstract:

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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10847 Inflammatory Cytokine (Interleukin-8): A Diagnostic Marker in Leukemia

Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

Abstract:

Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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10846 Protective Effects of Genistein against Cyclophosphamide-Induced Hepatotoxicity in Rats: Involvement of Anti-Inflammatory and Anti-Oxidant Activities

Authors: Dina F. Mansour, Dalia O. Saleh, Rasha E. Mostafa

Abstract:

Cyclophosphamide (CP), the most commonly used chemotherapeutic agent, was reported to cause many side effects including urotoxicity, cardiotoxicity, gonadotoxicity, and hepatotoxicity; this limits its clinical practice. In the present study, the protective effect of genistein (GEN), the major phytoestrogen in soy products that possesses various pharmacological activities, has been investigated against CP-induced acute liver damage in rats. Forty adult Sprague-Dawley rats were allocated into five groups. The first group received the vehicles and act as normal control. In the other groups, rats were injected with a single dose of CP (200 mg/kg, i.p). The last three groups were pretreated with subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Forty-eight hours following CP injection, rats of all groups were investigated for the serum levels of alanine transaminase and aspartate transaminase, as well as the liver contents of reduced glutathione, malondialdehyde, nitrite, interleukin-1β, and myeloperoxidase. Histopathological examination of liver tissues was also conducted. CP resulted in acute liver damage in rats as evidenced by alteration of liver function biomarkers, oxidative stress, and inflammatory markers; that was confirmed by the histopathological outcomes. Pretreatment of rats with GEN significantly protected against CP-induced deterioration of liver function and showed marked anti-oxidant and anti-inflammatory properties that were demonstrated by the biochemical and histopathological findings. In conclusion, the present findings demonstrated the protective effects of GEN against CP-induced liver damage and suggested role of its antioxidant and anti-inflammatory activities.

Keywords: cyclophosphamide, genistein, inflammation, interleukin-1β, liver, myeloperoxidase, oxidative stress

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10845 Correlation between the Levels of Some Inflammatory Cytokines/Haematological Parameters and Khorana Scores of Newly Diagnosed Ambulatory Cancer Patients

Authors: Angela O. Ugwu, Sunday Ocheni

Abstract:

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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10844 Cytokine Changes of Auricular Point Acupressure to Manage Aromatase Inhibitor-Induced Arthralgia in Postmenopausal Breast Cancer Survivors

Authors: Chao Hsing Yeh, Wei Chun Lin

Abstract:

Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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10843 Dietary N-6/N-3 PUFA Ratios Affect the Homeostasis of CD4+ T Cells in Mice with Dextran Sulfate Sodium-Induced Colitis

Authors: Cyoung-Huei Huang, Chiu-Li Yeh, Man-Hui Pai, Sung-Ling Yeh

Abstract:

This study evaluated the effect of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups in this study. Mice were fed for 24 d with an AIN-93G diet either with soybean oil (S), a mixture of soybean oil and low fish oil content (LF) or high fish oil content (HF). The ratio of n-6/n-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups provided 2% DSS in drinking water during day 15-19. All mice drank distilled water from day 20-24 for recovery and sacrificed on day 25. The results showed that colitis resulted in higher Th1, Th2, and Th17 and lower Treg percentages in the blood. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Further, the percentages of Th1, Th2, and Th17 cells in the blood were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with n-6/n-3 PUFA ratio 2:1 had more pronounce effects than ratio 4:1. These results suggest that diets with an n-6/n-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared to the n-6/n-3 PUFA ratio 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

Keywords: inflammatory bowel disease, n-3 polyunsaturated fatty acids, helper T lymphocyte, regulatory T lymphocyte

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10842 Detecting Potential Biomarkers for Ulcerative Colitis Using Hybrid Feature Selection

Authors: Mustafa Alshawaqfeh, Bilal Wajidy, Echin Serpedin, Jan Suchodolski

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Inflammatory Bowel disease (IBD) is a disease of the colon with characteristic inflammation. Clinically IBD is detected using laboratory tests (blood and stool), radiology tests (imaging using CT, MRI), capsule endoscopy and endoscopy. There are two variants of IBD referred to as Ulcerative Colitis (UC) and Crohn’s disease. This study employs a hybrid feature selection method that combines a correlation-based variable ranking approach with exhaustive search wrapper methods in order to find potential biomarkers for UC. The proposed biomarkers presented accurate discriminatory power thereby identifying themselves to be possible ingredients to UC therapeutics.

Keywords: ulcerative colitis, biomarker detection, feature selection, inflammatory bowel disease (IBD)

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10841 Therapeutic Evaluation of Bacopa Monnieri Extract on Liver Fibrosis in Rats

Authors: Yu Wen Wang, Shyh Ming Kuo, Hsia Ying Cheng, Yu Chiuan Wu

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Liver fibrosis is caused by the activation of hepatic stellate cells in the liver to secrete excessive and deposition of extracellular matrix. In recent years, many treatment strategies have been developed to reduce the activation of hepatic stellate cells and therefore to increase the decomposition of extracellular matrix. Bacopa monnieri, an herbaceous plant of the scrophulariaceae, containing saponins and glycosides, which with antioxidant, anti-inflammation, pain relief and free radical scavenging characteristics. This study was to evaluate the inhibition of hepatic stellate cell activity by Bacopa monnieri extract and its therapeutic potential in treating thioacetamide-induced liver fibrosis in rats. The results showed that the IC50 of Bacopa monnieri extract was 0.39 mg/mL. Bacopa monnieri extract could effectively reduce H2O2-induced hepatic stellate cells inflammation. In the TAA-induced liver fibrosis animal studies, albumin secretion recovered to normal level after treated with Bacopa monnieri extract for 2-w, and fibrosis related proteins, α-SMA and TGF-1levels decreased indicating the extract exerted therapeutic effect on the liver fibrosis. However, inflammatory factors TNF- obviously decreased after 4-w treatment. In summary, we could successfully extract the main component-Bacopaside I from the plant and acquired a potential therapy using this component in treating TAA-induced liver fibrosis in rat.

Keywords: anti-inflammatory, Bacopa monnieri, fibrosis, hepatic stellate cells, water extract

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10840 The Effects of Alpha-Lipoic Acid Supplementation on Post-Stroke Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors: Hamid Abbasi, Neda Jourabchi, Ranasadat Abedi, Kiarash Tajernarenj, Mehdi Farhoudi, Sarvin Sanaie

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Background: Alpha lipoic acid (ALA), fat- and water-soluble, coenzyme with sulfuret content, has received considerable attention for its potential therapeutic role in diabetes, cardiovascular diseases, cancers, and central nervous disease. This investigation aims to evaluate the probable protective effects of ALA in stroke patients. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, This meta-analysis was performed. The PICO criteria for this meta-analysis were as follows: Population/Patients (P: stroke patients); Intervention (I: ALA); Comparison (C: control); Outcome (O: blood glucose, lipid profile, oxidative stress, inflammatory factors).In addition, Studies that were excluded from the analysis consisted of in vitro, in vivo, and ex vivo studies, case reports, quasi-experimental studies. Scopus, PubMed, Web of Science, EMBASE databases were searched until August 2023. Results: Of 496 records that were screened in the title/abstract stage, 9 studies were included in this meta-analysis. The sample sizes in the included studies vary between 28 and 90. The result of risk of bias was performed via risk of bias (RoB) in randomized-controlled trials (RCTs) based on the second version of the Cochrane RoB assessment tool. 8 studies had a definitely high risk of bias. Discussion: To the best of our knowledge, The present meta-analysis is the first study addressing the effectiveness of ALA supplementation in enhancing post-stroke metabolic markers, including lipid profile, oxidative stress, and inflammatory indices. It is imperative to acknowledge certain potential limitations inherent in this study. First of all, type of treatment (oral or intravenous infusion) could alter the bioavailability of ALA. Our study had restricted evidence regarding the impact of ALA supplementation on included outcomes. Therefore, further research is warranted to develop into the effects of ALA specifically on inflammation and oxidative stress. Funding: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 72825). Registration: This study was registered in the International prospective register of systematic reviews (PROSPERO ID: CR42023461612).

Keywords: alpha-lipoic acid, lipid profile, blood glucose, inflammatory factors, oxidative stress, meta-analysis, post-stroke

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10839 The Prognostic Value of Dynamic Changes of Hematological Indices in Oropharyngeal Cancer Patients Treated with Radiotherapy

Authors: Yao Song, Danni Cheng, Jianjun Ren

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Objectives: We aimed to explore the prognostic effects of absolute values and dynamic changes of common hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients treated with radiation. Methods and materials: The absolute values of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline (within 45 days before radiation), 1-, 3-, 6- and 12-months after the start of radiotherapy were retrospectively collected. Locally-estimated smoothing scatterplots were used to describe the smooth trajectory of each index. A mixed-effect model with a random slope was fitted to describe the changing rate and trend of indices over time. Cox proportional hazard analysis was conducted to assess the correlation between hematological indices and treatment outcomes. Results: Of the enrolled 85 OPSCC patients, inflammatory indices, such as WBC and ALC, dropped rapidly during acute treatment and gradually recovered, while NLR and PLR increased at first three months and subsequently declined within 3-12 months. Higher absolute value or increasing trend of nutritional indices (Alb and Hb) was associated with better prognosis (all p<0.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (WBC, ANC, Plt, PLR and NLR) had worse survival (all p<0.05). Conclusions: The absolute values and dynamic changes of hematological indices were valuable prognostic factors for OPSCC patients who underwent radiotherapy.

Keywords: hematological indices, oropharyngeal cancer, radiotherapy, NLR, PLR

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10838 The Aminoguanidine Reduced NO Synthase Activity and Infiltration of Macrophages in Inflammation Induced by LPS in Rats

Authors: Hakim Chayeb

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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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10837 The Protective Effects of Naringenin on Iodoacetamide-Induced Ulcerative Colitis in Rats

Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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10836 Inhibitory Effect of Coumaroyl Lupendioic Acid on Inflammation Mediator Generation in Complete Freund’s Adjuvant-Induced Arthritis

Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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10835 The Gastroprotective Potential of Clematis Flammula Leaf Extracts

Authors: Dina Atmani-Kilani, Farah Yous, Djebbar Atmani

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The etiology of peptic ulcer is closely related to stress, excessive consumption of nonsteroidal anti-inflammatory drugs, or ethanol. Clematis flammula (Ranunculaceae) is a medicinal plant widely used by rural populations to treat inflammatory disorders. This study was designed to assess the gastroprotective potential of C. flammula extracts. Gastric ulcer was induced by stress, indomethacin, HCl / ethanol, and absolute ethanol on NMRI-type mice. The antioxidant potency of the ethanolic extract of Clematis flammula (EECF) was evaluated on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities. Glutathione (GSH) and malonaldehyde (MDA) levels were also quantified. The anti-inflammatory potential was evaluated through the effect of EECF on myeloperoxidase activity (MPO) and vascular permeability. Complementary tests concerning the quantification of mucus levels, gastric motility, inhibition of ATPase H+/K+activity, as well as a histopathological study were also undertaken to explore the mechanism of action of the EECF. The EECF exhibited a significant (p <0.001) and optimal (100 mg/kg) gastroprotective effect by elevating SOD, CAT, and GSH levels, thereby minimizing the production of MDA and lowering the activity of MPO and vascular permeability. EECF also increased the rate of mucus production, decreased gastric motility, and completely suppressed the H+/K+ ATPase activity. Histopathological study confirmed the effectiveness of the extract in the prevention of peptic ulcer. The results obtained in this study demonstrated the gastro-protective effect of EECF via acidic antioxidant, anti-inflammatory, cytoprotective and anti-secretory mechanisms, which may justify its use as a substitute in peptic ulcer treatment.

Keywords: clematis flammula, superoxide dismutase, myeloperoxidase, ATPase, pump

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10834 Enhanced Anti-Inflammatory and Antioxidant Activities of Perna canaliculus Oil Extract and Low Molecular Weight Fucoidan from Undaria pinnatifida

Authors: Belgheis Ebrahimi, Jun Lu

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

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10833 Study of Irritant and Anti-inflammatory Activity of Snuhi/Zaqqum (Euphorbia nerifolia) with Special Reference to Holy Quran and Ayurveda

Authors: Mohammed Khalil Ur Rahman, Pradnya Chigle, Bushra Farhen

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Indian mythology believes that Vedas are eternal treatises. Vedas are categorized into four divisions viz., Rigveda, Yajurveda, Samveda, Atharveda. All these spiritual classics not only deal with rituals and customs but also consist of inclusion of many references related to health. Out of these four, Atharveda deals with maximum principles pertaining to health sciences. Therefore, it is said that the science and the art of Ayurveda has developed from Atharveda. Ayurveda deals with many medicinal plants either as a single therapeutic use or in combination. One such medicinal plant is Snuhi (Euphorbia neriifolia Linn.) which finds its extensive importance along with Haridra and Apamargakshar, in the preparation of Ksharsutra which in turn is used for the treatment of Fistula in Ano. It is interesting to note that this plant Snuhi is also referred in Holy Quran as the Tree of Zaqqum advocated as the food for the sinners as a part of torment. The reference in Surat Ad-Dukhan is as follows: - 44:43-46. “Verily, the tree of Zaqqum will be the food of the sinners, Like boiling oil, it will boil in the bellies, like the boiling of scalding water.” The above verse implies that plant Snuhi/Zaqqum due to irritant property acts as a drastic purgative but at the same time it also possesses anti inflammatory properties in order to relieve the irritation. These properties of Zaqqum has been unfolded in the modern research which states that, Diterpene polycyclic esters are responsible for its toxic and irritant nature whereas; triterpenes are responsible for its anti inflammatory property. Present work will be an effort to review the concept of Quran about latex of the Tree of Zaqqum in terms of its phytochemistry and its therapeutic use in Ksharsutra pertaining to irritant and anti inflammatory property.

Keywords: ayurveda, Quran, zaqqum, ksharsutra, latex piles, inflammation

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10832 Determination of the Toxicity of a Lunar Dust Simulant on Human Alveolar Epithelial Cells and Macrophages in vitro

Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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10831 Chemical Composition and Biological Investigation of Halpophyllum tuberculatum A. Juss (Rutaceae) Essential Oils Growing in Libya

Authors: O. M. M. Sabry, Abeer M. El Sayed

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The essential oils from the aerial parts and flowers of Haplophyllum tuberculatum (Forsskal) Adr. Juss (Rutaceae) growing in Libya were obtained separately by hydro-distillation using a Clevenger-type apparatus. The essential oils yield were (0.4, 1.5w/w%) respectively based on the dry weight of the plant. The oils were analyzed by GC-MS. Twenty four constituents, amounting to 96.6%, were identified in the oil of the aerial parts. The predominant compounds were among the non oxygenated terpenoids (82.4%) as monoterpene hydrocarbons, represented by sabinen (26.4 %), δ-terpinen (26 %), β-phellandrene (10.4%) and 3-carene (3.86%). Zingiberine (0.4%) and β-sesquiphellandrene (0.12%) were the major sesquiterpene hydrocarbons identified. Oxygenated monoterpenes were represented by eucalyptol (5.5%) and piperitone (5.55%). Twenty six constituents, equivalent to 99.5%, were identified in the oil of the flowers. The dominance of monoterpene hydrocarbons in the flowers oil can be attributed to the high percentage of γ-terpinen (38.44%), β-phellandrene (10.0%), α- phellandrene (2.33%), 3,4-dimethyl-1,5-cyclooctadiene (6.67%), β-myrecene (6.04%), 3-carene (5.43%) and α-pinene (1.3%).While the oxygenated monoterpenes can be contributed to the trans-piperitol (4.67%) and piperitone (2.07%). Sesquiterpene hydrocarbons were not identified in the oil of the flower of H. tuberculatum. Variation in constitution between oils of Libyan H. tuberculatum and that obtained from other countries can be due to both environmental and genetic factors. The essential oils have demonstrated variable antimicrobial activities against certain micro-organisms. Also have revealed marked in vitro cytotoxicity against lung (H1299), liver (HEPG2) carcinoma cell line and variably effective as anti-inflammatory and antioxidant.

Keywords: Halpophyllum tuberculatum, rutaceae, essential oil, antimicrobial, anti-inflammatory, antitumor, antioxidant, Libya

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