Displaying publications 1 - 20 of 56 in total

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  1. Wickramatilake CM, Mohideen MR, Pathirana C
    Ann Endocrinol (Paris), 2015 Jul;76(3):260-3.
    PMID: 26142486 DOI: 10.1016/j.ando.2015.04.008
    OBJECTIVE: There is limited data on the assessment of relationship between sex hormones, metabolic syndrome (MS) and inflammation. Therefore, our objective was to examine the relationship between metabolic syndrome, testosterone and inflammation.
    PATIENTS AND METHODS: It was a cross-sectional study which included 309 subjects in the age range of 30-70years. Blood was analyzed for plasma glucose, serum lipids, total testosterone (TT) and high-sensitivity C-reactive protein (hs-CRP).
    RESULTS: There were 153 patients with metabolic syndrome and 156 without MS according to modified NCEP guidelines. Age, BMI, obesity, dyslipidaemia, smoking (OR=2.35, CI=1.35-4.09), LDL-Ch, low TT (OR=0.76, CI=0.38-1.52) and elevated hs-CRP (OR=1.56, CI=0.87-2.80) were significant independent predictors of MS (all P<0.05).
    CONCLUSIONS: The low testosterone and high hs-CRP levels are independent predictors of metabolic syndrome.
    KEYWORDS: Hommes; Inflammation; Men; Metabolic syndrome; Syndrome métabolique; Testosterone; Testostérone
    Matched MeSH terms: Inflammation/pathology
  2. Chong ZX, Yeap SK, Ho WY
    Arch Biochem Biophys, 2020 11 30;695:108583.
    PMID: 32956633 DOI: 10.1016/j.abb.2020.108583
    miRNAs are short non-coding RNA molecules that regulate the expression of mRNA post-transcriptionally. MiRNAs that are secreted into the circulation, also termed circulating miRNAs, have been studied extensively for their roles in diagnosis, treatment and prognosis of human breast cancer. Breast cancer is the most prevalent female cancer and is associated with key cancer hallmarks including sustained proliferation, evasion of apoptosis, increased invasion, enhanced metastases, initation of inflammation, induction of angiogenesis, metabolic derangement and immune dysregulation. This review aimed to explore the relationships between circulating miRNAs and different breast cancer hallmarks. Besides, the advantages, challenges and clinical application of using circulating miRNAs in human breast cancer management were also discussed.
    Matched MeSH terms: Inflammation/pathology
  3. Nna VU, Bakar ABA, Ahmad A, Mohamed M
    Arch Physiol Biochem, 2020 Dec;126(5):377-388.
    PMID: 30513216 DOI: 10.1080/13813455.2018.1543329
    Context: Metformin's effect on glycaemic control is well documented, but its effect on diabetes-induced testicular impairment has been scarcely reported.Objective: To investigate the effects of metformin on testicular oxidative stress, inflammation, and apoptosis, which largely contribute to fertility decline in diabetic state.Methods: Male Sprague-Dawley rats were divided into 3 groups (n = 6/group) namely: normal control (NC), diabetic control (DC), and metformin (300 mg/kg b.w./d)-treated diabetic groups. Metformin was administrated for 4 weeks.Results: Decreased mRNA expressions and activities of antioxidant enzymes were seen in the testes of DC group. mRNA and protein expressions of pro-inflammatory and pro-apoptotic markers increased, while interleukin-10 and proliferating cell nuclear antigen (PCNA) decreased in the testes of DC group. Treatment with metformin up-regulated antioxidant enzymes, down-regulated inflammation, and apoptosis and increased PCNA immunoexpression in the testes.Conclusions: Metformin protects the testes from diabetes-induced impairment and may improve male reproductive health in diabetic state.
    Matched MeSH terms: Inflammation/pathology
  4. Ankathil R, Mustapha MA, Abdul Aziz AA, Mohd Shahpudin SN, Zakaria AD, Abu Hassan MR, et al.
    Asian Pac J Cancer Prev, 2019 06 01;20(6):1621-1632.
    PMID: 31244280 DOI: 10.31557/APJCP.2019.20.6.1621
    AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308
    G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in
    Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560
    study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP
    and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined
    using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of
    genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes
    IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on
    the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A
    alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based
    on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF – α 308 G>A contribute
    to a significantly higher risk among male and female who are more than 50 years and for smokers in this population.
    Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308
    G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response
    genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic
    predisposition factors for CRC in Malaysian population.
    Matched MeSH terms: Inflammation/pathology*
  5. Muthuraju S, Zakaria R, Karuppan MKM, Al-Rahbi B
    Biomed Res Int, 2020 03 05;2020:9231452.
    PMID: 32219147 DOI: 10.1155/2020/9231452
    Matched MeSH terms: Inflammation/pathology
  6. Adam SH, Giribabu N, Kassim N, Kumar KE, Brahmayya M, Arya A, et al.
    Biomed Pharmacother, 2016 Jul;81:439-452.
    PMID: 27261624 DOI: 10.1016/j.biopha.2016.04.032
    INTRODUCTION: Protective effects of Vitis Vinifera seed aqueous extract (VVSAE) against pancreatic dysfunctions and elevation of oxidative stress, inflammation and apoptosis in the pancreas in diabetes were investigated. Histopathological changes in the pancreas were examined under light microscope.

    METHODS: Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-α, Ikkβ and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti-oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract.

    RESULTS: GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-α, Ikkβ and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities.

    CONCLUSION: In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes.

    Matched MeSH terms: Inflammation/pathology
  7. Lee NT, Ong LK, Gyawali P, Nassir CMNCM, Mustapha M, Nandurkar HH, et al.
    Biomolecules, 2021 07 06;11(7).
    PMID: 34356618 DOI: 10.3390/biom11070994
    The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.
    Matched MeSH terms: Inflammation/pathology
  8. Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S
    Bone, 2018 11;116:8-21.
    PMID: 29990585 DOI: 10.1016/j.bone.2018.07.003
    Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.
    Matched MeSH terms: Inflammation/pathology
  9. Che Ahmad Tantowi NA, Lau SF, Mohamed S
    Calcif. Tissue Int., 2018 10;103(4):388-399.
    PMID: 29808374 DOI: 10.1007/s00223-018-0433-1
    Osteoporosis (OP) and osteoarthritis (OA) are debilitating musculoskeletal diseases of the elderly. Ficus deltoidea (FD) or mistletoe fig, a medicinal plant, was pre-clinically evaluated against OP- and OA-related bone alterations, in postmenopausal OA rat model. Thirty twelfth-week-old female rats were divided into groups (n = 6). Four groups were bilateral ovariectomized (OVX) and OA-induced by intra-articular monosodium iodoacetate (MIA) injection into the right knee joints. The Sham control and OVX-OA non-treated groups were given deionized water. The three other OVX-OA groups were orally administered daily with FD extract (200, 400 mg/kg) or diclofenac (5 mg/kg) for 4 weeks. The rats' bones and blood were evaluated for protein and mRNA expressions of osteoporosis and inflammatory indicators, and micro-CT computed tomography for bone microstructure. The non-treated OVX-OA rats developed severe OP bone loss and bone microstructural damage in the subchondral and metaphyseal regions, supported by reduced serum bone formation markers (osteocalcin, osteoprotegerin) and increased bone resorption markers (RANKL and CTX-I). The FD extract significantly (p 
    Matched MeSH terms: Inflammation/pathology*
  10. Ose J, Schock H, Tjønneland A, Hansen L, Overvad K, Dossus L, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Jun;24(6):951-61.
    PMID: 25855626 DOI: 10.1158/1055-9965.EPI-14-1279-T
    BACKGROUND: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.

    METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.

    RESULTS: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity ≤ 0.01].

    CONCLUSIONS: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity.

    IMPACT: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

    Matched MeSH terms: Inflammation/pathology
  11. Lee CY
    Clin Exp Pharmacol Physiol, 2013 Jun;40(6):385-91.
    PMID: 23586523 DOI: 10.1111/1440-1681.12096
    Psychosocial stress is reported to be one of the main causes of obesity. Based on observations in studies that relate stress and gut inflammation to obesity, the present study hypothesized that chronic stress, via inflammation, alters the expression of nutrient transporters and contributes to the development of metabolic syndrome. Rats were exposed to restraint stress for 4 h/day for 5 days/week for eight consecutive weeks. Different segments of rat intestine were then collected and analysed for signs of pathophysiological changes and the expression of Niemann-Pick C1-like-1 (NPC1L1), sodium-dependent glucose transporter-1 (SLC5A1, previously known as SGLT1) and facilitative glucose transporter-2 (SLC2A2, previously known as GLUT2). In a separate experiment, the total anti-oxidant activity (TAA)-time profile of control isolated intestinal segments was measured. Stress decreased the expression of NPC1L1 in the ileum and upregulated SLC5A1 in both the jejunum and ileum and SLC2A2 in the duodenum. Inflammation and morphological changes were observed in the proximal region of the intestine of stressed animals. Compared with jejunal and ileal segments, the rate of increase in TAA was higher in the duodenum, indicating that the segment contained less anti-oxidants; anti-oxidants may function to protect the tissues. In conclusion, stress alters the expression of hexose and lipid transporters in the gut. The site-specific increase in the expression of SLC5A1 and SLC2A2 may be correlated with pathological changes in the intestine. The ileum may be protected, in part, by gut anti-oxidants. Collectively, the data suggest that apart from causing inflammation, chronic stress may promote sugar uptake and contribute to hyperglycaemia.
    Matched MeSH terms: Inflammation/pathology
  12. Bindal P, Gnanasegaran N, Bindal U, Haque N, Ramasamy TS, Chai WL, et al.
    Clin Oral Investig, 2019 Oct;23(10):3821-3831.
    PMID: 30687907 DOI: 10.1007/s00784-019-02811-5
    OBJECTIVE: In this study, we aimed to determine the suitable concentrations of human platelet lysate (HPL) and platelet-rich plasma (PRP) for maintaining the in vitro proliferative and angiogenic potential of inflamed dental pulp stem cells.

    MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced inflamed dental pulp-derived stem cells (iDPSCs) were treated with different concentrations of HPL and PRP (10% and 20%) followed by determination of viability using Alamar Blue assay. Expression of angiogenesis-, adhesion-, and inflammation-regulating genes was also analyzed using RT-qPCR array. Furthermore, expression of growth factors at protein level in the cell culture microenvironment was measured using multiplex assay.

    RESULTS: Viability of iDPSCs was significantly (p 

    Matched MeSH terms: Inflammation/pathology*
  13. Tumpang MA, Ramli NA, Hussain Z
    Curr Drug Targets, 2018;19(6):674-700.
    PMID: 28914203 DOI: 10.2174/1389450118666170913162147
    BACKGROUND: Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD.

    OBJECTIVE: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy.

    RESULTS: The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies.

    CONCLUSION: In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents.

    Matched MeSH terms: Inflammation/pathology
  14. Ansari SA, Devi S, Tenguria S, Kumar A, Ahmed N
    Cytokine, 2014 Aug;68(2):110-7.
    PMID: 24767863 DOI: 10.1016/j.cyto.2014.03.006
    HP0986 protein of Helicobacter pylori has been shown to trigger induction of proinflammatory cytokines (IL-8 and TNF-α) through the activation of NF-κB and also to induce Fas mediated apoptosis of human macrophage cells (THP-1). In this study, we unravel mechanistic details of the biological effects of this protein in a murine macrophage environment. Up regulation of MCP-1 and TNF-α in HP0986-induced RAW 264.7 cells occurred subsequent to the activation and translocation of NF-κB to the cell nucleus. Further, HP0986 induced apoptosis of RAW 264.7 cells through Fas activation and this was in agreement with previous observations made with THP-1 cells. Our studies indicated activation of TNFR1 through interaction with HP0986 and this elicited the aforementioned responses independent of TLR2, TLR4 or TNFR2. We found that mouse TNFR1 activation by HP0986 facilitates formation of a complex comprising of TNFR1, TRADD and TRAF2, and this occurs upstream of NF-κB activation. Furthermore, FADD also forms a second complex, at a later stage, together with TNFR1 and TRADD, resulting in caspase-8 activation and thereby the apoptosis of RAW 264.7 cells. In summary, our observations reveal finer details of the functional activity of HP0986 protein in relation to its behavior in a murine macrophage cell environment. These findings reconfirm the proinflammatory and apoptotic role of HP0986 signifying it to be an important trigger of innate responses. These observations form much needed baseline data entailing future in vivo studies of the functions of HP0986 in a murine model.
    Matched MeSH terms: Inflammation/pathology*
  15. Haque N, Khan IM, Abu Kasim NH
    Cytokine, 2019 08;120:144-154.
    PMID: 31071675 DOI: 10.1016/j.cyto.2019.04.018
    The immunomodulatory properties of mesenchymal stem cells (MSCs) from autologous and allogeneic sources are useful in stimulating tissue regeneration and repair. To obtain a high number of MSCs for transplantation requires extensive in vitro expansion with culture media supplements that can cause xeno-contamination of cells potentially compromising function and clinical outcomes. In this study stem cells from human extracted deciduous teeth (SHED) were cultured in Knockout™ DMEM supplemented with either pooled human serum (pHS) or foetal bovine serum (FBS) to compare their suitability in maintaining immunomodulatory properties of cells during in vitro expansion. No significant difference in cell survival of SHED grown in pHS (pHS-SHED) or FBS (FBS-SHED) was observed when co-cultured with complement, monocytes or lymphocytes. However, significant changes in the expression of sixteen paracrine factors involved in immunomodulation were observed in the supernatants of FBS-SHED co-cultures with monocytes or lymphocytes compared to that in pHS-SHEDs after both 24 and 120 h of incubation. Further analysis of changing protein levels of paracrine factors in co-cultures using biological pathway analysis software predicted upregulation of functions associated with immunogenicity in FBS-SHED and lymphocyte co-cultures compared to pHS-SHED co-cultures. Pathway analysis also predicted significant stimulation of HMGB1 and TREM1 signalling pathways in FBS-SHED co-cultures indicating activation of immune cells and inflammation. Though FBS supplementation does not impact survival of SHED, our combinatorial biological pathway analysis supports the idea that in vitro expansion of SHEDs in pHS provides optimal conditions to minimise xeno-contamination and inflammation and maintain their immunomodulatory properties.
    Matched MeSH terms: Inflammation/pathology
  16. Phyu WK, Ong KC, Wong KT
    Emerg Microbes Infect, 2017 Jul 12;6(7):e62.
    PMID: 28698666 DOI: 10.1038/emi.2017.49
    Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.
    Matched MeSH terms: Inflammation/pathology
  17. Tham CL, Liew CY, Lam KW, Mohamad AS, Kim MK, Cheah YK, et al.
    Eur J Pharmacol, 2010 Feb 25;628(1-3):247-54.
    PMID: 19958764 DOI: 10.1016/j.ejphar.2009.11.053
    Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE(2) but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-alpha and IL-6 were moderately inhibited whereas IL-8 and IL-1beta were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.
    Matched MeSH terms: Inflammation/pathology
  18. Paudel YN, Angelopoulou E, Piperi C, Balasubramaniam VRMT, Othman I, Shaikh MF
    Eur J Pharmacol, 2019 Sep 05;858:172487.
    PMID: 31229535 DOI: 10.1016/j.ejphar.2019.172487
    High mobility group box 1 (HMGB1) is a ubiquitous protein, released passively by necrotic tissues or secreted actively by stressed cells. Extracellular HMGB1 is a typical damage-associated molecular pattern (DAMP) molecule which generates different redox types through binding with several receptors and signalling molecules, aggravating a range of cellular responses, including inflammation. HMGB1 is reported to participate in the pathogenesis of inflammatory diseases, through the interaction with pivotal transmembrane receptors, including the receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4). This review aims to highlight the role of HMGB1 in the innate inflammatory response describing its interaction with several cofactors and receptors that coordinate its downstream effects. Novel and underexplored HMGB1 binding molecules that have been actively involved in HMGB1-mediated inflammatory diseases/conditions with therapeutic potential are further discussed.
    Matched MeSH terms: Inflammation/pathology
  19. Ooi TC, Chan KM, Sharif R
    Immunopharmacol Immunotoxicol, 2017 Oct;39(5):259-267.
    PMID: 28697633 DOI: 10.1080/08923973.2017.1344987
    CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer.

    OBJECTIVE: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages.

    MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay.

    RESULTS: Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine.

    CONCLUSION: Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

    Matched MeSH terms: Inflammation/pathology
  20. Bokhari RA, Tantowi NACA, Lau SF, Mohamed S
    Inflammopharmacology, 2018 Aug;26(4):939-949.
    PMID: 29380171 DOI: 10.1007/s10787-017-0432-2
    The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis (OA) was investigated in explant cartilage culture and in postmenopausal OA rat model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was induced after surgical recovery, by intra-articular injection of monosodium iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA-related parameters and biomarkers. The OSA reduced proteoglycan and ROS release from the cartilage explants under inflammatory (IL-1b) conditions. In the OA-induced rats' cartilages, the OSA downregulated the mRNA expressions for IL-1β, IL-6, IL-10, TNF-α, NF-κβ, NOS2, PTGS2, PTGER2, ACAN, COL2A1, MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced the OA rats' serum levels for PGE2, CTX-II, TNF-α, MMP1, MMP13, PIINP, OPG, RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage degradation, inflammation, collagenase/aggrecanase activities, to improve joint and subchondral bone structure. O. stamineus mitigated osteoarthritis by downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to about 30 mg/kg for humans.
    Matched MeSH terms: Inflammation/pathology
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