Displaying publications 361 - 380 of 479 in total

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  1. Chin VK, Asyran AMY, Zakaria ZA, Abdullah WO, Chong PP, Nordin N, et al.
    J Parasit Dis, 2019 Mar;43(1):139-153.
    PMID: 30956457 DOI: 10.1007/s12639-018-1070-3
    Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic target for various inflammatory diseases. Despite that, the role of TREM-1 during malaria pathogenesis remains obscure with present literature suggesting a link between TREM-1 with severe malaria development. Therefore, this study aims to investigate the role of TREM-1 and TREM-1 related drugs during severe malaria infection in Plasmodium berghei-infected mice model. Our findings revealed that TREM-1 concentration was significantly increased throughout the infection periods and TREM-1 was positively correlated with malaria parasitemia development. This suggests a positive involvement of TREM-1 in severe malaria development. Meanwhile, blocking of TREM-1 activation using rmTREM-1/Fc and TREM-1 clearance by mTREM-1/Ab had significantly reduced malaria parasitemia and suppressed the production of pro- inflammatory cytokines (TNF-α, IL-6 and IFN-γ) and anti-inflammatory cytokine (IL-10). Furthermore, histopathological analysis of TREM-1 related drug treatments, in particular rmTREM-1/Fc showed significant improvements in the histological conditions of major organs (kidneys, spleen, lungs, liver and brain) of Plasmodium berghei-infected mice. This study showed that modulation of TREM-1 released during malaria infection produces a positive outcome on malaria infection through inhibition of pro-inflammatory cytokines secretion and alleviation of histopathological conditions of affected organs. Nevertheless, further investigation on its optimal dosage and dose dependant study should be carried out to maximise its full potential as immunomodulatory or as an adjuvant in line with current antimalarial agents.
    Matched MeSH terms: Cytokines
  2. Siti Noor Syuhada Muhammad Amin, Noor Suryani Mohd Ashari, Wan Zuraida Wan Abd. Hamid, Azriani Ab Rahman, Azman Azid
    Interleukin 31 (IL-31)is one of the cytokines which appears to be an important regulator of Th2 responses. Previous study has been done to determine IL-31 serums levels in atopic dermatitis (AD). However, the serum levels of IL-31 in allergic rhinitis (AR) and atopic asthma (AA) is not many reported and still unclear. The objective of this cross sectional study is to determine an association between IL-31 and other predisposing factors with allergic diseases in HRPZ II (Hospital Raja PerempuanZainab II) and HUSM (Hospital UniversitiSains), Kelantan, Malaysia. This study involved 70 patients of AD, 70 patients of AR, 70 patients of AA and 70 healthy controls from staffs and people in HUSM.Five milliliters of blood were withdrawn and centrifuged for 5 minutes at 2000 rpm to obtain the serum and analyzed for IL-31 levels by using enzymelinked immunosorbent (ELISA) kits (Human IL 31 Duoset, R&D System). Simple and multiple logistic regressions were used to analyze the association between IL-31 levels and predisposing factors among allergic diseases. The levels of IL-31 and other predisposing factors showed significant associations in smoking status, occupational exposure and area of living for AD and AR, however in AA, the significant association only found in smoking status and occupational exposure. In conclusion, we found that there were associations between IL-31 serum levels and other predisposing factors with AD, AR and AA. The findings can be the pilot study to determine IL-31 levels in allergic diseases in Malaysia.
    Matched MeSH terms: Cytokines
  3. Malik A, Ashraf MAB, Khan MW, Zahid A, Shafique H, Waquar S, et al.
    Arch Environ Contam Toxicol, 2020 Apr;78(3):329-336.
    PMID: 31620805 DOI: 10.1007/s00244-019-00673-2
    The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5 years of outdoor experience and Hb levels
    Matched MeSH terms: Cytokines
  4. Zaharuddin L, Mokhtar NM, Muhammad Nawawi KN, Raja Ali RA
    BMC Gastroenterol, 2019 Jul 24;19(1):131.
    PMID: 31340751 DOI: 10.1186/s12876-019-1047-4
    BACKGROUND: Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 1010 cfu Lactobacillus and Bifidobacteria strains for six months on clinical outcomes and inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22) in patients with colorectal cancer.

    METHODS: Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit.

    RESULTS: The majority of cases (~ 70%) were in Duke's C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P 

    Matched MeSH terms: Cytokines
  5. Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF
    Rev Med Virol, 2019 09;29(5):e2073.
    PMID: 31369184 DOI: 10.1002/rmv.2073
    Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
    Matched MeSH terms: Cytokines
  6. Mohd Sahardi NFN, Makpol S
    PMID: 31531114 DOI: 10.1155/2019/5054395
    Currently, the age of the population is increasing as a result of increased life expectancy. Ageing is defined as the progressive loss of physiological integrity, which can be characterized by functional impairment and high vulnerability to various types of diseases, such as diabetes, hypertension, Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerosis. Numerous studies have reported that the presence of oxidative stress and inflammation contributes to the development of these diseases. In general, oxidative stress could induce proinflammatory cytokines and reduce cellular antioxidant capacity. Increased oxidative stress levels beyond the production of antioxidant agents cause oxidative damage to biological molecules, including DNA, protein, and carbohydrates, which affects normal cell signalling, cell growth, differentiation, and apoptosis and leads to disease pathogenesis. Since oxidative stress and inflammation contribute to these diseases, ginger (Zingiber officinale Roscoe) is one of the potential herbs that can be used to reduce the level of oxidative stress and inflammation. Ginger consists of two major active components, 6-gingerol and 6-shogaol, which are essential for preventing oxidative stress and inflammation. Thus, this paper will review the effects of ginger on ageing and degenerative diseases, including AD, PD, type 2 diabetes mellitus (DM), hypertension, and osteoarthritis.
    Matched MeSH terms: Cytokines
  7. Rajandram R, Perumal K, Yap NY
    Transl Androl Urol, 2019 May;8(Suppl 2):S138-S146.
    PMID: 31236331 DOI: 10.21037/tau.2018.11.10
    Obesity is a recognized risk factor for renal cell carcinoma (RCC) the commonest form of kidney cancer. Both obesity and RCC are serious diseases with increasing incidence yearly. This review examined certain obesity associated measurements and adipokines as detection/prognostic indicators for RCC. The obesity related measurements such as body mass index (BMI), waist circumstance (WC), waist-hip ratio (WHR) in predicting RCC are valid when used in conjunction with other risk factors such as age and sex or with histological findings. The adipokine adiponectin holds promising outcomes as a predictive marker in assessing the risk of developing RCC. In addition, tissue leptin/leptin receptor may be a distinguishing marker for RCC subtypes. However, circulating leptin may not be a suitable detection or prognostic biomarker for RCC. The other less investigated adipokines; omentin, visfatin, apelin and resistin are also expressed in RCC but their prognostic capabilities are still inconclusive. BMI, WC and adipokines may be useful additions in a nomogram which includes TNM staging and pathological grading system to detect, confirm and follow-up RCC cases.
    Matched MeSH terms: Cytokines
  8. Ong HK, Yong CY, Tan WS, Yeap SK, Omar AR, Razak MA, et al.
    Vaccines (Basel), 2019 08 19;7(3).
    PMID: 31430965 DOI: 10.3390/vaccines7030091
    Current seasonal influenza A virus (IAV) vaccines are strain-specific and require annual reconstitution to accommodate the viral mutations. Mismatches between the vaccines and circulating strains often lead to high morbidity. Hence, development of a universal influenza A vaccine targeting all IAV strains is urgently needed. In the present study, the protective efficacy and immune responses induced by the extracellular domain of Matrix 2 protein (M2e) displayed on the virus-like particles of Macrobrachium rosenbergii nodavirus (NvC-M2ex3) were investigated in BALB/c mice. NvC-M2ex3 was demonstrated to be highly immunogenic even in the absence of adjuvants. Higher anti-M2e antibody titers corresponded well with increased survival, reduced immunopathology, and morbidity of the infected BALB/c mice. The mice immunized with NvC-M2ex3 exhibited lower H1N1 and H3N2 virus replication in the respiratory tract and the vaccine activated the production of different antiviral cytokines when they were challenged with H1N1 and H3N2. Collectively, these results suggest that NvC-M2ex3 could be a potential universal influenza A vaccine.
    Matched MeSH terms: Cytokines
  9. Choy KW, Murugan D, Leong XF, Abas R, Alias A, Mustafa MR
    Front Pharmacol, 2019;10:1295.
    PMID: 31749703 DOI: 10.3389/fphar.2019.01295
    Cardiovascular diseases (CVDs) such as angina, hypertension, myocardial ischemia, and heart failure are the leading causes of morbidity and mortality worldwide. One of the major transcription factors widely associated with CVDs is nuclear factor-kappa B (NFκB). NFκB activation initiates the canonical and non-conical pathways that promotes activation of transcription factors leading to inflammation, such as leukocyte adhesion molecules, cytokines, and chemokines. Flavonoids are bioactive polyphenolic compounds found abundantly in various fruits, vegetables, beverages (tea, coffee), nuts, and cereal products with cardiovascular protective properties. Flavonoids can be classified into six subgroups based on their chemical structures: flavanones, flavones, flavonols, flavan-3-ols, isoflavones, and anthocyanidins. As NFκB inhibitors, these flavonoids may modulate the expression of pro-inflammatory genes leading to the attenuation of the inflammatory responses underlying various cardiovascular pathology. This review presents an update on the anti-inflammatory actions of flavonoids via inhibition of NFκB mechanism supporting the therapeutic potential of these natural compounds in various CVDs.
    Matched MeSH terms: Cytokines
  10. Muthusami S, Vidya B, Shankar EM, Vadivelu J, Ramachandran I, Stanley JA, et al.
    Curr Protein Pept Sci, 2020;21(1):52-65.
    PMID: 31702489 DOI: 10.2174/1389203720666191106113435
    Hormones are known to influence various body systems that include skeletal, cardiac, digestive, excretory, and immune systems. Emerging investigations suggest the key role played by secretions of endocrine glands in immune cell differentiation, proliferation, activation, and memory attributes of the immune system. The link between steroid hormones such as glucocorticoids and inflammation is widely known. However, the role of peptide hormones and amino acid derivatives such as growth and thyroid hormones, prolactin, dopamine, and thymopoietin in regulating the functioning of the immune system remains unclear. Here, we reviewed the findings pertinent to the functional role of hormone-immune interactions in health and disease and proposed perspective directions for translational research in the field.
    Matched MeSH terms: Cytokines/genetics; Cytokines/immunology; Cytokines/metabolism
  11. Siti Sarah CO, Md Shukri N, Mohd Ashari NS, Wong KK
    PeerJ, 2020;8:e9834.
    PMID: 32953271 DOI: 10.7717/peerj.9834
    Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.
    Matched MeSH terms: Cytokines
  12. Jafri MA, Kalamegam G, Abbas M, Al-Kaff M, Ahmed F, Bakhashab S, et al.
    Front Cell Dev Biol, 2019;7:380.
    PMID: 32010693 DOI: 10.3389/fcell.2019.00380
    Osteoarthritis (OA) is a chronic degenerative joint disorder associated with degradation and decreased production of the extracellular matrix, eventually leading to cartilage destruction. Limited chondrocyte turnover, structural damage, and prevailing inflammatory milieu prevent efficient cartilage repair and restoration of joint function. In the present study, we evaluated the role of secreted cytokines, chemokines, and growth factors present in the culture supernatant obtained from an ex vivo osteochondral model of cartilage differentiation using cartilage pellets (CP), bone marrow stem cells (BM-MSCs), and/or BM-MSCs + CP. Multiplex cytokine analysis showed differential secretion of growth factors (G-CSF, GM-CSF, HGF, EGF, VEGF); chemokines (MCP-1, MIP1α, MIP1β, RANTES, Eotaxin, IP-10), pro-inflammatory cytokines (IL-1β, IL-2, IL-5, IL-6, IL-8, TNFα, IL-12, IL-15, IL-17) and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) in the experimental groups compared to the control. In silico analyses of the role of stem cells and CP in relation to the expression of various molecules, canonical pathways and hierarchical cluster patterns were deduced using the Ingenuity Pathway Analysis (IPA) software (Qiagen, United States). The interactions of the cytokines, chemokines, and growth factors that are involved in the cartilage differentiation showed that stem cells, when used together with CP, bring about a favorable cell signaling that supports cartilage differentiation and additionally helps to attenuate inflammatory cytokines and further downstream disease-associated pro-inflammatory pathways. Hence, the autologous or allogeneic stem cells and local cartilage tissues may be used for efficient cartilage differentiation and the management of OA.
    Matched MeSH terms: Cytokines
  13. Nur Ramziahrazanah Jumat, Pei Shin Chai, Chiew Yee Loh, Sharmili Vidyadaran, Zainina Seman
    MyJurnal
    Introduction: Immune response against viral infections and tumors not only requires the recruitment of immune cells but also cytokines. Cytokine dysregulation is associated with inflammatory diseases such as cancer, autoimmune diseases, infections and allergy. Intake of fruit and vegetables are known not only to reduce inflammation but may also provide protection against various diseases. Methods: Effects of selected fruits and herbs on cytokines profile of IL-8, IL-1β, IL-6, IL-10, TNF and IL-12p70 were examined using the CBA flow cytometric assay. Peripheral blood mononuclear cells (PBMC) obtained from blood samples of twelve healthy subjects aged 20 to 30 years [males = 6 and females = 6] were treated with papaya, mata kucing, dang shen and pu-erh tea, respectively, for 6 and 48 hours at various concentrations. In vivo effects was further tested on healthy volunteers [males = 2, females = 4] by 2-days consumption of papaya following 2-days washout period without papaya. The diet of volunteers was controlled with fixed meals. Results:In vitro results after 6 hours of culture showed that papaya-treated PBMC significantly increased IL-8, IL-1β and IL-6 but reduced IL-10. Mata kucing-treated PBMC significantly increased IL-8 but reduced IL-6 while pu-erh tea significantly reduced IL-8, IL-1β, IL-6 and TNF. Cytokine analysis for dang shen-treated PBMC was only conducted at 48 hours. After 48 hours, papaya extract significantly reduced IL-8, IL-6 (8000 μg/ml), IL-10 and TNF. Significant increase of IL-6 was observed at 4000 and 16000 μg/ml. Mata kucing extract significantly increased IL-1β, IL-6 but reduced TNF. Significant increase of TNF was observed at 16000 μg/ml. Dang shen and pu-erh tea reduced IL-8, IL-1β, IL-6, IL-10 and TNF. However, in vivo papaya consumption did not show any significant changes and levels were low. Conclusion: This study showed fruits such as papaya and mata kucing had both stimulatory and inhibitory effect on various pro-inflammatory cytokines while effect of herbs such as dang shen and pu-erh tea were inhibitory. Immunomodulatory studies of natural food such as fruits and herbs may provide better understanding and subsequently improve management of inflammatory diseases.
    Matched MeSH terms: Cytokines
  14. Siti Zuleha Idris, Stephnie Yiau Kang Xian, Lee CinDee, Eusni Rahayu Mohd. Tohit, Chang Kian Meng, Maha Abdullah
    MyJurnal
    Introduction: Protein and gene expressions are intensively profiled for potential biomarkers in diagnosis or prognosis of diseases. The correlation between corresponding protein and mRNA of a gene is important to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. mRNA profiling is more commonly utilised as this method is cheaper and the technology more advanced. Acute myeloid leukaemia (AML) is a heterogeneous group of malignant precursors of the myeloid lineage that leads to death if not treated. Cytokines and death receptors are commonly evaluated in this disease in search of potential biomarkers; however, the mRNA/protein correlations of these biomarkers are still unclear. Methods: Semi-quantitative expression of mRNA expression and protein levels of IL-1β, IL-18Rα, IL-6, TNF-α and DR5 were measured by conventional polymerase reaction (PCR) and flow cytometry in 11 cases of AML at diagnosis. Correlation in the intensity of the PCR amplicon and corre-sponding mean fluorescence intensity of protein was determined by Spearman’s rank correlation test. Results: None of the cytokines/death receptor was significantly correlated except IL-6 (Rs= -0.6287, p=0.038). Unexpectedly, this was also a significant negative correlation. Conclusion: For the majority of selected biomarkers in AML, whether secreted or surface-expressed, mRNA and protein expressions were not significantly correlated. The strong negative correlation for IL-6 is worth further investigation.
    Matched MeSH terms: Cytokines
  15. Pei-Shin, Chai, Siti Zuleha Idris, Norfarazieda Hassan, Nur Ramziahrazana Jumat, Zainina Seman, Sharmili Vidyadaran, et al.
    MyJurnal
    The immune system responds to stimulus by activation/increase or inhibition/decrease in activities. These immu-nomodulatory effects may be triggered by various factors in the environment including cytokines, hormones and growth factors, as well as flavonoids, antioxidants and various antigens in food and the environment. Immunosup-pression has a direct effect on the capacity of the immune system to fight against infection and cancer formation. A pro-inflammatory response, however, may induce further progression of tumours that had formed. Inflammation is also associated with many chronic illnesses including pain. The suppressive effects from phytochemicals have been shown in the potential to reduce T-lymphocyte proliferation in vitro and in vivo. Studies have demonstrated inhibi-tion of pro-inflammatory cytokines from flavonoid such as naringenin, green tea polyphenol extract, encapsulated fruit and vegetable juice powder concentrate. Feijoa sellowiana Berg var. coolidge fruit juice consumption exerted anti-inflammatory activity on edema-induced mice within first hour of treatment while agipenin, a natural flavonoid reduced neuroinflammation by protection against damage from dendritic cells stimulated T cells in experimental autoimmune encephalomyelitis mouse models. Dietary polyphenols were found to exert a regulatory role on den-dritic cell function. Our own study showed immunosuppressive effect from increased T regulatory cells from papaya consumption. Increased regulatory cells are associated with cancer conditions. On the other hand, grape juice con-sumption mobilized gamma–delta T cells. Ginseng berry extract increased pro-inflammatory molecules in dendritic cells in the spleen while polysaccharide fractions from Momorica charantia, an edible medicinal vegetable increased various immune indexes. Fruits may also have endo-immunomodulatory function causing differential effects in male and female. Sex hormones can influence immune changes based on sex as seen in increased NK cells in males and antibodies in females. We observed a population of CD4-CD45RA-CD69+CD25- cells was significantly lower in males. However, none of these studies have been directly conducted on cancers. Investigation into this area may help improve decision making in cancer management.
    Matched MeSH terms: Cytokines
  16. Chung CH, Bretherton B, Zainalabidin S, Deuchars SA, Deuchars J, Mahadi MK
    Front Neurosci, 2020;14:906.
    PMID: 33013299 DOI: 10.3389/fnins.2020.00906
    Background: Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure.

    Main Body: Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway.

    Conclusion: Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury.

    Matched MeSH terms: Cytokines
  17. Chin SP, Mohd-Shahrizal MY, Liyana MZ, Then KY, Cheong SK
    Stem Cells Int, 2020;2020:8877003.
    PMID: 33061992 DOI: 10.1155/2020/8877003
    Background: Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α).

    Results: 11 healthy subjects (LD, n = 5; HD, n = 6; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA (705 ± 160 vs. 306 ± 36 pg/mL; p = 0.02) and IL-10 (321 ± 27 vs. 251 ± 28 pg/mL; p = 0.02); and lower levels of proinflammatory marker TNF-α (74 ± 23 vs. 115 ± 15 pg/mL; p = 0.04) compared to LD group.

    Conclusion: Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

    Matched MeSH terms: Cytokines
  18. Bonavina L, Fisichella PM, Gavini S, Lee YY, Tatum RP
    Ann N Y Acad Sci, 2020 12;1481(1):117-126.
    PMID: 32266986 DOI: 10.1111/nyas.14350
    In symptomatic young patients with gastroesophageal reflux symptoms, early identification of progressive gastroesophageal reflux disease (GERD) is critical to prevent long-term complications associated with hiatal hernia, increased esophageal acid and nonacid exposure, release of proinflammatory cytokines, and development of intestinal metaplasia, endoscopically visible Barrett's esophagus, and dysplasia leading to esophageal adenocarcinoma. Progression of GERD may occur in asymptomatic patients and in those under continuous acid-suppressive medication. The long-term side effects of proton-pump inhibitors, chemopreventive agents, and radiofrequency ablation are contentious. In patients with early-stage disease, when the lower esophageal sphincter function is still preserved and before endoscopically visible Barrett's esophagus develops, novel laparoscopic procedures, such as magnetic and electric sphincter augmentation, may have a greater role than conventional surgical therapy. A multidisciplinary approach to GERD by a dedicated team of gastroenterologists and surgeons might impact the patients' lifestyle, the therapeutic choices, and the course of the disease. Biological markers are needed to precisely assess the risk of disease progression and to tailor surveillance, ablation, and management.
    Matched MeSH terms: Cytokines
  19. Daftarian N, Zandi S, Piryaie G, Nikougoftar Zarif M, Ranaei Pirmardan E, Yamaguchi M, et al.
    FASEB J, 2020 Jun;34(6):8001-8011.
    PMID: 32333612 DOI: 10.1096/fj.201901902RR
    Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P 
    Matched MeSH terms: Cytokines
  20. Abdalla LF, Chaudhry Ehsanullah R, Karim F, Oyewande AA, Khan S
    Cureus, 2020 May 22;12(5):e8240.
    PMID: 32582499 DOI: 10.7759/cureus.8240
    The process of inflammation occurs due to inflammatory mediators, including prostaglandins, cytokines, and tumor necrosis factor (TNF). All these mediators activate the process of tumorigenesis and dysplasia, leading to colitis-associated cancer. Several drugs used to decrease these mediators will help in the treatment of acute attacks and also help in prolonged remissions of the disease by using nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and biological factors. Reducing these inflammatory mediators also have a role in chemoprevention and prevent progression to colorectal carcinoma. The most researched drugs in this process of chemoprevention are NSAIDs as it has both cyclooxygenase-2 (COX-2) inhibitory and non-inhibitory effects. These drugs should be taken for a long time and in large doses to reach this effect, which puts the patient at risk for various side effects. Researchers will need to do more research in the future to find the lowest effective dose that can reach the chemopreventive effect. We used database Pubmed as the main source for data search and extracted articles exploring the relationship between NSAIDs and their role in chemoprevention of colorectal carcinoma in inflammatory bowel disease (IBD) patients. We chose 23 studies which included seven review articles. We found that inflammatory mediators have a key role in colitis-associated cancer.
    Matched MeSH terms: Cytokines
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