Displaying publications 1 - 20 of 56 in total

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  1. Fulltext Impact of gentamicin coadministration along with high fructose feeding on progression of renal failure and metabolic syndrome in Sprague-Dawley rats
    Ibraheem ZO, Basir R, Aljobory AKh, Ibrahim OE, Alsumaidaee A, Yam MF
    Biomed Res Int, 2014;2014:823879.
    PMID: 25045706 DOI: 10.1155/2014/823879
    The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180-200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G) was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.
  2. Fulltext Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway
    Zakaria ZA, Roosli RAJ, Marmaya NH, Omar MH, Basir R, Somchit MN
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059475 DOI: 10.3390/biom10020280
    Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.
  3. Anti-malarial and cytokine-modulating effects of andrographolide in a murine model of malarial infection
    Hassan WRM, Basir R, Ali AH, Embi N, Sidek HM
    Trop Biomed, 2019 Sep 01;36(3):776-791.
    PMID: 33597499
    Malarial pathogenesis involves among others, uncontrolled or excessive cytokine production arising from dysregulated immune responses mounted by the host to eliminate the plasmodial parasite. The ubiquitous serine/threonine kinase, glycogen synthase kinase3β (GSK3β) is a crucial regulator of the balance between pro- and anti-inflammatory cytokine productions in the inflammatory response to pathogenic infections. Andrographolide, a bioactive compound in Andrographis paniculata, displays GSK3- inhibitory effects. A previous study elsewhere has shown that this compound has antimalarial activity but the molecular basis of its action is yet to be elucidated. Here we aimed to study the anti-malarial activity of andrographolide in a murine model of malarial infection to investigate whether its mechanism of action involves cytokine modulation and inhibition of GSK3β. Andrographolide showed strong and selective anti-plasmodial activity (IC50 = 13.70±0.71 µM; SI = 30.43) when tested against cultures of P. falciparum 3D7. Intraperitoneal administration of andrographolide (5 mg/kg body weight (bw)) into P. berghei NK65-infected ICR mice resulted in chemo-suppression of 60.17±2.12%, and significantly (P<0.05) improved median survival time of infected mice compared to nontreated control. In addition, andrographolide treatment significantly (P<0.05) decreased the level of serum pro-inflammatory cytokine, IFN-γ (1.4-fold) whilst the anti-inflammatory cytokines, IL-10 and IL-4 were increased 2.3- and 2.6-fold respectively. Western blot analyses revealed that andrographolide treatment of P. berghei NK65-infected mice resulted in an increased level of phosphorylated GSK3β (Ser9) in liver of infected mice. Andrographolide administration also decreased the levels of phosphorylated NF-κB p65 (Ser536) and phosphorylated Akt (Ser473) in liver of malaria- infected animals. Taken together, our findings demonstrate that the cytokine-modulating effect of andrographolide in experimental malarial infection involves at least in part inhibition of NF-κB activation as a consequence of GSK3β inhibition. Based on its cytokine-modulating effects, andrographolide is thus a plausible candidate for adjunctive therapy in malaria subject to clinical evaluations.
  4. The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β
    Ali AH, Sudi S, Basir R, Embi N, Sidek HM
    J Med Food, 2017 Feb;20(2):152-161.
    PMID: 28146408 DOI: 10.1089/jmf.2016.3813
    Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.
  5. Pathology and Host Immune Evasion During Human Leptospirosis: a Review
    Chin VK, Basir R, Nordin SA, Abdullah M, Sekawi Z
    Int Microbiol, 2020 May;23(2):127-136.
    PMID: 30875033 DOI: 10.1007/s10123-019-00067-3
    Human leptospirosis is considered as one of the most widespread and potentially fatal zoonotic diseases that causes high mortality and morbidity in the endemic regions of tropical and subtropical countries. The infection can arise from direct or indirect exposure of human through contaminated environment that contains leptospires or animal reservoirs that carry leptospires. The clinical manifestations during human leptospirosis ranges from asymptomatic, mild infections to severe and life-threatening complications involving multi-organ failures with kidneys, lungs and liver severely affected. Despite much efforts have been put in to unravel the pathogenesis during human leptospirosis, it remains obscure to which extent the host factors or the pathogen itself contribute towards the pathogenesis. Host innate immunity, especially, polymorphonuclear neutrophils and complement system are involved in the first line of defense during human leptospirosis. However, pathogenic Leptospira has acquired diverse evasion strategies to evade from host immunity and establish infection in infected hosts. Hence, in this review, we focus on organs pathology during human leptospiral infection and host evasion strategies employed by Leptospira. A profound understanding on leptospiral immunity and how Leptospira subvert the immune system may provide new insights on the development of therapeutic regimens against this species in future.
  6. Fulltext Remarkable Anticancer Activity of Teucrium polium on Hepatocellular Carcinogenic Rats
    Movahedi A, Basir R, Rahmat A, Charaffedine M, Othman F
    Evid Based Complement Alternat Med, 2014;2014:726724.
    PMID: 25197311 DOI: 10.1155/2014/726724
    The term cancer has been concomitant with despair, agony, and dreadful death. Like many other diseases, herbal therapy has been used to prevent or suppress cancer. The present study investigated the capability of the decoction of Teucrium polium L. from Lamiaceae family to protect liver cells against hepatocellular carcinoma in carcinogenesis-induced animal model. After 28 weeks of treatment with decoction of Teucrium polium L., serum biochemical markers including ALT, AST, AFP, GGT, ALP, HCY, TNF-α, α2MG, and CBG have been regulated auspiciously. Total antioxidant status also has been increased intensely. Liver lesion score in treated group was lessened and glucocorticoid activity has been intensified significantly. In conclusion, Teucrium polium L. decoction might inhibit or suppress liver cancer development.
  7. Fulltext Receptor for advanced glycation end products and its involvement in inflammatory diseases
    Chuah YK, Basir R, Talib H, Tie TH, Nordin N
    Int J Inflam, 2013;2013:403460.
    PMID: 24102034 DOI: 10.1155/2013/403460
    The receptor for advanced glycation end products (RAGE) is a transmembrane receptor of the immunoglobulin superfamily, capable of binding a broad repertoire of ligands. RAGE-ligands interaction induces a series of signal transduction cascades and lead to the activation of transcription factor NF-κB as well as increased expression of cytokines, chemokines, and adhesion molecules. These effects endow RAGE with the role in the signal transduction from pathogen substrates to cell activation during the onset and perpetuation of inflammation. RAGE signaling and downstream pathways have been implicated in a wide spectrum of inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's disease, arthritis, acute respiratory failure, and sepsis. Despite the significant progress in other RAGE studies, the functional importance of the receptor in clinical situations and inflammatory diseases still remains to be fully realized. In this review, we will summarize current understandings and lines of evidence on the molecular mechanisms through which RAGE signaling contributes to the pathogenesis of the aforementioned inflammation-associated conditions.
  8. Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite
    Abdullahi SA, Unyah NZ, Nordin N, Basir R, Nasir WM, Alapid AA, et al.
    Mini Rev Med Chem, 2020;20(9):739-753.
    PMID: 31660810 DOI: 10.2174/1389557519666191029105736
    Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.
  9. Fulltext Toxoplasma gondii induced cognitive impairment in rats via dysregulation of dopamine receptors and indoleamine 2,3 dioxygenase
    Wana MN, Watanabe M, Chiroma SM, Unyah NZ, Abdullahi SA, Nordin S, et al.
    Heliyon, 2023 Mar;9(3):e14370.
    PMID: 36950587 DOI: 10.1016/j.heliyon.2023.e14370
    Toxoplasma gondii (T. gondii) is a parasite capable of residing in the brain of their host which influences behaviour changes due to alterations in the neurotransmitters. Consequently, dopamine receptors (DRD) and indoleamine 2, 3 dioxygenase (IDO) dysregulation facilitate the progression of behaviour changes in a host as a response to infection. This study tested the effect of neurotransmitter changes as a result of T. gondii infection on rats cognitive impairment. The T. gondii strain of type I, II and III from Malaysia were previously identified by standard procedures. Sporulated oocysts each of type I, II and III were inoculated separately into three groups of Wistar rats (n = 9) respectively. Two separate control groups received either phosphate buffered saline (PBS) or MK-801 (dizocilpine). Behaviour changes were evaluated at nine weeks post infection in a square box, elevated plus maze and gene expression level of DRD and IDO compounds. The study revealed increased fatal feline attraction, reduced anxiety, decreased DRD and increased IDO gene expression in the T. gondii infected groups and MK-801 compared to the PBS control group. In conclusion, T. gondii infection alter the level of neurotransmitters in rat which cause cognitive impairment. This implies that all the T. gondii strain can cause behaviour changes if human were infected.
  10. Fulltext Susceptibility of Toxoplasma gondii to Ethanolic Extract of Tinospora crispa in Vero Cells
    Sharif AA, Unyah NZ, Nordin N, Basir R, Wana MN, Alapid Ahmad A, et al.
    Evid Based Complement Alternat Med, 2019;2019:2916547.
    PMID: 31827548 DOI: 10.1155/2019/2916547
    Background: Toxoplasmosis remains widely distributed globally and is one of the major neglected parasitic zoonotic infections. The infection is still endemic in most parts of the world due to poor control as well as challenges of the currently used medications which can be overcome by using natural products. This study evaluated the effect of ethanolic extract from the stem of Tinospora crispa (EETC) on host cell invasion and intracellular replication of Toxoplasma gondii.

    Method: The stem powder of T. crispa was soaked in absolute ethanol for 72 hours. The resulting ethanolic extract was screened for the presence of phytochemicals. Vero cells monolayer in 96-well plate was infected with RH strain of T. gondii and treated with concentrations of the EETC, Veratrine alkaloid, and clindamycin ranging from 1.56 to 200 μg/mL. MTT assay was conducted after 24 hours to evaluate the cytotoxicity and antiparasitic activities of the EETC. Four and 24 hours treatment models were adapted to assess the infection index and intracellular proliferation of T.

    Results: The study revealed that the EETC had no cytotoxic effects on Vero cells with IC50 = 179 μg/mL, as compared to clindamycin (IC50 = 116.5 μg/mL) and Veratrine alkaloid (IC50 = 60.4 μg/mL). The EETC had good anti-toxoplasma activities with IC50 = 6.31 μg/mL in comparison with clindamycin (IC50 = 8.33 μg/mL) and Veratrine alkaloid (IC50 = 14.25 μg/mL). The EETC caused more than 70% and 80% reduction in infection index and intracellular proliferation in both treatment models, respectively.

    Conclusion: This in vitro study showed that the EETC contains promising phytochemicals effective against T. gondii and safe to the host cells.

  11. Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: A narrative review
    Lee TY, Farah N, Chin VK, Lim CW, Chong PP, Basir R, et al.
    Nutr Res, 2023 Nov;119:1-20.
    PMID: 37708600 DOI: 10.1016/j.nutres.2023.08.010
    Riboflavin is a precursor of the essential coenzymes flavin mononucleotide and flavin adenine dinucleotide. Both possess antioxidant properties and are involved in oxidation-reduction reactions, which have a significant impact on energy metabolism. Also, the coenzymes participate in metabolism of pyridoxine, niacin, folate, and iron. Humans must obtain riboflavin through their daily diet because of the lack of programmed enzymatic machineries for de novo riboflavin synthesis. Because of its physiological nature and fast elimination from the human body when in excess, riboflavin consumed is unlikely to induce any negative effects or develop toxicity in humans. The use of riboflavin in pharmaceutical and clinical contexts has been previously explored, including for preventing and treating oxidative stress and reperfusion oxidative damage, creating synergistic compounds to mitigate colorectal cancer, modulating blood pressure, improving diabetes mellitus comorbidities, as well as neuroprotective agents and potent photosensitizer in killing bloodborne pathogens. Thus, the goal of this review is to provide a comprehensive understanding of riboflavin's biological applications in medicine, key considerations of riboflavin safety and toxicity, and a brief overview on the nanoencapsulation of riboflavin for various functions including the treatment of a range of diseases, photodynamic therapy, and cellular imaging.
  12. Fulltext Comparison of pathogenesis of P. Berghei infection in mouse and rat models
    Chin, V.K., Chong, W.C., Hassan, H., Zakaria, Z.A., Nordin, N., Basir, R., et al.
    JUMMEC, 2019;22(2):4-12.
    MyJurnal
    Background: The cytokine cascade in the immunopathogenesis of malaria infection had been widely studied.
    However, their specific association with survival and severe infection remained obscure.

    Methods: The study investigated the cytokine profiles and histopathological features of malaria in the severe
    infection and survival models by using male ICR mice and male Sprague Dawley rats respectively.

    Results: The severe model, the infected ICR mice, exhibited a high parasitemia with 100% mortality after
    peak parasitemia at day 5 post-infection. The survival model, the infected Sprague Dawley rats, showed
    mild parasitemia with full recovery by day 14 of infection. Both severe and survival models showed similar
    histopathological severity during peak parasitemia. The severe model produced highly elevated levels of proinflammatory
    cytokines, TNF-α and IL-1α, and low levels of the anti-inflammatory cytokine, IL-4; while the
    survival model showed low levels of TNF-α and IL-1α with high levels of IL-4.

    Conclusion: There were differences in the pathogenesis of the severe and survival models of malaria infection.
    These could be a basis for immunotherapy of malaria in the future.
  13. Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract
    Yam MF, Basir R, Asmawi MZ, Ismail Z
    Am J Chin Med, 2007;35(1):115-26.
    PMID: 17265556
    Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.
  14. Menhaden fish oil attenuates postpartum depression in rat model via inhibition of NLRP3-inflammasome driven inflammatory pathway
    Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, Adenan MI, Ismail A, Basir R, et al.
    J Tradit Complement Med, 2021 Sep;11(5):419-426.
    PMID: 34522636 DOI: 10.1016/j.jtcme.2021.02.007
    Background and aim: Postpartum depression (PPD) is a familiar problem which is associated with about 10-20% of women after child delivery. Fish oil (FO) has a therapeutic potentials to many diseases including mood disorders. However, there is paucity of data on the effects of FO supplementation on PPD rat model. Hence, this study aimed at investigating the potentials of FO in ameliorating depressive-like behaviors in PPD rat by evaluating the involvement of NLRP3-inflammasome.

    Experimental procedure: Thirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1-3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4-6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR).

    Results: PPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1β and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities.

    Conclusion: In conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1β activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats.

  15. GSK3β: A plausible molecular target in the cytokinemodulating effect of exogenous insulin in a murine model of malarial infection
    Aizuddin NNF, Ganesan N, Ng WC, Ali AH, Ibrahim I, Basir R, et al.
    Trop Biomed, 2020 Dec 01;37(4):1105-1116.
    PMID: 33612762 DOI: 10.47665/tb.37.4.1105
    Malaria is a life-threatening disease caused by the Plasmodium sp. parasite. Infection results in heightened pro-inflammatory response which contributes to the pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed therapy is a plausible approach. Glycogen synthase kinase-3β (GSK3β), a serine/threonine kinase plays a pivotal role in the regulation of inflammatory response during pathogenic infections. The present study was conducted to investigate the chemo-suppressive and cytokine-modulating effects of insulin administration in malaria-infected mice and the involvement of GSK3β. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice resulted in chemo-suppression exceeding 60% and improved median survival time of infected mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control). Western analysis revealed that pGSK3β (Ser9) intensity in brain samples from insulin-treated (0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than that in control. In liver samples, pGSK3β (Ser9) intensity from insulin-treated infected mice were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities (to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times)) whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3β and consequent inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic for malaria.
  16. Fulltext Eradication of malaria through genetic engineering: the current situation
    Chong WC, Basir R, Fei YM
    Asian Pac J Trop Med, 2013 Feb;6(2):85-94.
    PMID: 23339908 DOI: 10.1016/S1995-7645(13)60001-2
    Malaria is an intra-cellular parasitic protozoon responsible for millions of deaths annually. Host and parasite genetic factors are crucial in affecting susceptibility to malaria and progression of the disease. Recent increased deployment of vector controls and new artemisinin combination therapies have dramatically reduced the mortality and morbidity of malaria worldwide. However, the gradual emergence of parasite and mosquito resistance has raised alarm regarding the effectiveness of current artemisinin-based therapies. In this review, mechanisms of anti-malarial drug resistance in the Plasmodium parasite and new genetically engineered tools of research priorities are discussed. The complexity of the parasite lifecycle demands novel interventions to achieve global eradication. However, turning laboratory discovered transgenic interventions into functional products entails multiple experimental phases in addition to ethical and safety hurdles. Uncertainty over the regulatory status and public acceptance further discourage the implementation of genetically modified organisms.
  17. IL-8 as a potential in-vitro severity biomarker for dengue disease
    Soo KM, Tham CL, Khalid B, Basir R, Chee HY
    Trop Biomed, 2019 Dec 01;36(4):1027-1037.
    PMID: 33597472
    Dengue is a common infection, caused by dengue virus. There are four different dengue serotypes, with different capacity to cause severe dengue infections. Besides, secondary infections with heterologous serotypes, concurrent infections of multiple dengue serotypes may alter the severity of dengue infection. This study aims to compare the severity of single infection and concurrent infections of different combinations of dengue serotypes in-vitro. Human mast cells (HMC)-1.1 were infected with single and concurrent infections of multiple dengue serotypes. The infected HMC-1.1 supernatant was then added to human umbilical cord vascular endothelial cells (HUVEC) and severity of dengue infections was measured by the percentage of transendothelial electrical resistance (TEER). Levels of IL10, CXCL10 and sTRAIL in HMC-1.1 and IL-8, IL-10 and CXCL10 in HUVEC culture supernatants were measured by the ELISA assays. The result showed that the percentage of TEER values were significantly lower in single infections (p< 0.05), compared to concurrent infections on day 2 and 3, indicating that single infection increase endothelial permeability greater than concurrent infections. IL-8 showed moderate correlation with endothelial permeability (r > 0.4), indicating that IL-8 may be suitable as an in-vitro severity biomarker. In conclusion, this in-vitro model presented few similarities with regards to the conditions in dengue patients, suggesting that it could serve as a severity model to test for severity and levels of severity biomarkers upon different dengue virus infections.
  18. Fulltext Meta-analysis of biomarkers for severe dengue infections
    Soo KM, Khalid B, Ching SM, Tham CL, Basir R, Chee HY
    PeerJ, 2017;5:e3589.
    PMID: 28929009 DOI: 10.7717/peerj.3589
    BACKGROUND: Dengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI.

    METHODS: Data concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines. The keywords "(IL1* or IL-1*) AND (dengue*)" were used and the same process was repeated for other potential biomarkers, according to Medical Subject Headings terms suggested by PubMed and Ovid. Meta-analysis of the mean difference in plasma or serum level of biomarkers between DF and SDI patients was performed, separated by different periods of time (days) since fever onset. Subgroup analyses comparing biomarker levels of healthy plasma and sera controls, biomarker levels of primary and secondary infection samples were also performed, as well as analyses of different levels of severity and biomarker levels upon infection by different dengue serotypes.

    RESULTS: Fifty-six studies of 53 biomarkers from 3,739 dengue cases (2,021 DF and 1,728 SDI) were included in this meta-analysis. Results showed that RANTES, IL-7, IL-8, IL-10, IL-18, TGF-b, and VEGFR2 levels were significantly different between DF and SDI. IL-8, IL-10, and IL-18 levels increased during SDI (95% CI, 18.1-253.2 pg/mL, 3-13 studies, n = 177-1,909, I(2) = 98.86%-99.75%). In contrast, RANTES, IL-7, TGF-b, and VEGFR2 showed a decrease in levels during SDI (95% CI, -3238.7 to -3.2 pg/mL, 1-3 studies, n = 95-418, I(2) = 97.59%-99.99%). Levels of these biomarkers were also found to correlate with the severity of the dengue infection, in comparison to healthy controls. Furthermore, the results showed that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 display peak differences between DF and SDI during or before the critical phase (day 4-5) of SDI.

    DISCUSSION: This meta-analysis suggests that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 may be used as potential early laboratory biomarkers in the diagnosis of SDI. This can be used to predict the severity of dengue infection and to monitor the effectiveness of treatment. Nevertheless, methodological and reporting limitations must be overcome in future research to minimize variables that affect the results and to confirm the findings.
  19. Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice
    Jabbarzare M, Chin VK, Talib H, Yam MF, Adam SK, Hassan H, et al.
    Iran J Parasitol, 2015 Jul-Sep;10(3):389-401.
    PMID: 26622294
    Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice.
  20. Fulltext Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum
    Ibraheem ZO, Abd Majid R, Noor SM, Sedik HM, Basir R
    Malar Res Treat, 2014;2014:950424.
    PMID: 25506039 DOI: 10.1155/2014/950424
    Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
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