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- PublicationThe effect of CRX-527 on pro-inflammatory cytokine production against mycobacterium bovis BCG clone expressing the c-terminus of merozoite surface protein-1 of plasmodium falciparum(2021-10)Malaria infection is a leading cause of mortality and morbidity in African and Southeast Asian countries. TLR-4 has been shown to be important in malaria immunity and can be possibly use as an adjuvant to enhance the long-lasting immune response against BCG-MSP1C. This research was conducted to determine the effects of toll-like receptor 4 (TLR-4) agonist, CRX527, on cellular and humoral immune response against Mycobacterium bovis bacille Calmette-Guérin (BCG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum (BCG-MSP1C). In this study six groups of mice (n=6 per group) were injected with 200 μl intraperitoneal phosphate buffered saline T80 (PBS-T80), 200 μl of PBS-T80 containing 2 x 106 cfu/ml of BCG or rBCG in the presence or absence of CRX527. Blood was collected from the tail veins of the mice before the start of the immunisation and 4 weeks after each immunisation. Enzyme linked immunosorbent assay (ELISA) was carried out to measure the production of TNF-α and IL-12 in the sera of the immunized mice. The findings showed that the sera of rBCG without CRX immunised group yielding the most increase in IL-12 followed by the mice injected with rBCG with CRX. In contrast, the entire mice immunised groups showed decrease production for TNF-α after the immunisation. Therefore, this combination of rBCG with TLR4 agonist can be used to create a vaccine that capable of inducing a strong and long-lasting immunity to allow the immune system to be prepared for the emergence of multidrug-resistant strains of malaria diseases.
- PublicationElucidation of the vasorelaxation mechanisms induced by syzygium polyanthum leaves aqueous extract(2021-08)Previous studies have demonstrated that aqueous extract of Syzygium polyanthum leaves (AESP) has vasorelaxation activity. However, there is still very little information on its mechanism of action on direct vasorelaxation activity. Therefore, the present study was designed to determine endothelium-dependant relaxation of the AESP and investigated the mechanism of vasorelaxation. The in vitro method was utilised, mounting the aortic ring into myograph, precontracted with phenylephrine (1 μM) and studied based on the agonist-antagonist inhibition protocols. The endothelium-dependant was studied on endothelium intact and denuded thoracic arterial ring isolated from Wistar-Kyoto (WKY) rats. The vasorelaxation mechanisms of AESP were evaluated on the endothelial-intact aortic rings. This study shown that the AESP relaxation was endothelium-dependant. The vasorelaxant effect of AESP was attenuated by L-NAME (endothelial nitric oxide synthase/eNOS inhibitor, 100 μM) and ODQ (soluble guanylate cyclase/sGC inhibitor, 10 μM). However, methylene blue (cyclic guanosine monophosphate/cGMP lowering agent, 10 μM) and indomethacin (non-selective COX inhibitor, 10 μM) did not produce significant inhibition on the AESP relaxation. Taken together, the findings indicated that vasorelaxation of AESP was endothelium-dependent, through NO/eNOS and sGC pathways.
- PublicationEvaluation of Hibiscus Sabdariffa L. calyx as cardioprotective agents(2021-10)Cardiovascular diseases (CVD), particularly Myocardial Infarction (MI), are the leading cause of mortality and morbidity worldwide. Hypercholesterolaemia increased the risk of developing CVD. Hibiscus sabdariffa L. (Roselle) has been used traditionally to reduce cholesterol levels. However, there is limited evidence of the plant's cardioprotective effects. The present study evaluated the effects of the aqueous extract of H. sabdariffa calyx (AEHS) on hypercholesterolaemia-myocardial infarction (HC-MI) rats. The proximate analysis was conducted to determine the nutritional composition of a self-made high-cholesterol diet (HCD). There are three phases in the animal study. The first phase (induction phase) was aim to develop an HC rat model using HCD for 6 weeks. The second phase (intervention phase) was to evaluate the effects of 30 days of AEHS treatment on body mass index (BMI), fasting blood sugar (FBS), fasting cholesterol (FC) and systolic blood pressure (SBP) in the rat. The third phase is where isoprenaline induced the myocardial infarction in rats (HC-MI) at day- 29 and 30. Although the cholesterol level was normal in HC-MI rats, there was a fatty change in the liver (steatosis). The HC-MI rat was also established based on raised cardiac troponin T level and the necrotic changes on the left ventricle tissue. However, AEHS did not significantly improve the parameters in the intervention phase. Moreover, AEHS did not reduce the cardiac troponin T significantly compared to the untreated-HC-MI, which is concurrent with the histology of the left ventricle. However, RFT and LFT were normal in AEHS-treated HC-MI. Collectively, further studies are needed to elucidate H. sabdariffa as a cardioprotective agent.
- PublicationDevelopment and optimization of rapid resolution liquid chromatography (RRLC) method following solid-phase extraction for determination of anthocyanin in rat plasma(2021-08)The growing interest of anthocyanins in roselle has brought upon the importance of the compound’s analysis to investigate its pharmacological properties. Sensitive and specific analytical methods are required to accurately analyse the anthocyanin present in the sample. In this study, rapid resolution liquid chromatography (RRLC) was used to analyse cyanidin-3-O-glucoside chloride, one of the anthocyanins found in roselle. Spectrophotometric analysis and optimization of chromatographic conditions were performed to develop a suitable and precise RRLC method for the determination of the selected anthocyanin. Both liquid-liquid extraction (LLE) and solid-phase extraction (SPE) method were performed to evaluate the best extraction method of anthocyanin in the rat plasma sample. The optimised chromatographic method demonstrated that the mobile phase composition of 0.1% trifluoroacetic acid aqueous solution and acetonitrile in the ratio of 81:19, respectively with a flow rate of 0.5 mL/min, at 30°C column temperature and detection wavelength of 525 nm were suitable for RRLC analysis of cyanidin-3-O-glucoside chloride. SPE was chosen as the final extraction method in the study as it produced better peaks in the chromatogram compared to LLE. In conclusion, the developed RRLC method in this study can be used to determine anthocyanins in the future pharmacokinetic study of roselle.
- PublicationEvaluation of the male reproductive toxicity of the anthocyanin-rich standardized extract of hibiscus sabdariffa L.loaded niosomes in sprague dawley rats(2021-08)Hibiscus sabdariffa has long been widely utilised for medicinal purposes. Aqueous extract of H. sabdariffa encapsulated in niosome (AEHS-Nio) was formulated to improve the effectiveness of this plant extract. It was administered to forty male Sprague Dawley rats at four different dosages 0 (control), 250, 500, and 1000 mg/kg/day by oral gavage for 63 days to evaluate the potential effects of AESHNio on the male reproductive system. A substantial number of parameters were evaluated throughout the treatment period that was comprised of three phases; premating, mating, and post-mating. Results obtained demonstrated that the effects of AEHS-Nio on the male rat reproductive system were slightly significant for certain doses. No mortality and any signs of physical toxicity were observed. The mating performance was also not affected. However, due to the established anti-obesity effects of H. sabdariffa extract, the bodyweight of rats were considerably changed. As a consequence, the reproductive organ weights were found to be statistically different. Furthermore, AEHS-Nio increased the testosterone levels and sperm counts of the 250 and 1000 mg/kg dose groups, while the 500 mg/kg dose group showed considerably low levels for both parameters. The 500 mg/kg dose group was detected to exhibit inconsistent data for certain parameters when compared to other groups, which might be caused by confounding factors instead of AEHS-Nio. Therefore, the current data suggest that AEHS-Nio did not toxic to the reproductive system of male rats. Nevertheless, AEHS-Nio should be consumed with caution as long as the dose administered does not exceed 250 mg/kg of bodyweight a day.The human risk on male reproductive parameters associated with its use should also be reasonably estimated.
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- PublicationZinc removal from the industrial wastewater using activated carbon synthesized from mangrove(2021-06-01)Most of wastewater effluent contains dangerous heavy metals that must be appropriately handled. Heavy metal pollution is a serious problem in developing countries, as most industrial operations have increased heavy metal contamination in lakes, rivers, and other water sources. Thus, a substantial amount of research has been performed on low-cost adsorbents to examine their potential in heavy metal removal. As a result, a summary and assessment of mangrove as a low-cost adsorbent have been completed in this report. This study assesses the potential of activated carbon derived from mangroves for the removal of a specific heavy metal, zinc. Aside from that, the examination of the key factors that impact heavy metal removal, which are the effect of temperature, initial concentration, and contact duration on heavy metal removal, is also being examined. The adsorption capacity increased with the increase of initial concentration of Zn2+ from 1 ppm to 7 ppm resulted in an increase in adsorption capacity from 0.1604 mg/g to 1.1627 mg/g. As the temperature raised from 30°C to 60°C, the adsorption capability of Zn2+ were decreased indicating the process was exothermic. The capacity for Zn2+ adsorption reduced from 1.241 mg/g to 1.1627 mg/g as the temperature increased. For adsorption isotherm model, Freundlich isotherm model at temperature of 60°C is more suitable to describe Zn2+ adsorption on mangrove activated carbon due to higher correlation coefficient, R2 value at 0.5984. The correlation coefficient, R2 from the pseudo second order model for Zn2+ adsorption was 0.9959 which is higher than pseudo-first order model, 0.9695. This indicate that pseudo-second order is more suitable more kinetic adsorption model for Zn2+ adsorption.
- PublicationLocal Government Administration And Rural Transformation In Nasarawa State, Nigeria(2023-08)There is an interface that exists between government at the rural or grass root level and rural transformation or development which is the main reason why Local Government Administrations were established all over the world. This research work seeks to examine the role of Local Government Administrations in Rural Development in Nasarawa State, Nigeria, with a particular focus on three key variables of rural development which are: Agriculture, Health and Education. The main objectives of this study are (i) to examine the extent to which Local Government Administrations in Nasarawa state have contributed to Rural Development in terms of Agriculture, Health and Education, (ii) to investigate the factors responsible for the underdevelopment of the rural areas in Nasarawa state in terms of Agriculture, Health and Education, (iii) to suggest the ways forward on how the rural areas of Nasarawa state can be better developed. The study employed the qualitative research method, where an in- depth interview was conducted. The data were coded and analyzed using the thematic analysis with the help of Nvivo 12 software. The findings in the study reveal that local government administrations in Nasarawa state have failed to deliver on their mandate of developing the rural areas as expected of them, most especially in the areas of Agriculture, Health and Education. The study therefore recommends that the Local Government Administrations in the state should do their best by ensuring good service delivery in the rural areas in terms of Agriculture, Health, and Education.
- PublicationThe determination of agreement between transducer-like enhancer split-1 (TLE-1) and fluorescence in situ hybridization (fish) in synovial sarcoma cases(2018)The emergence of transducer-like enhancer of split 1 (TLE-1) as a new immunohistochemical (IHC) marker for synovial sarcoma (SS) have recently offered an alternative diagnostic strategy to pathologists in differentiating SS from other histologic mimics. Our major aim is to determine the agreement between TLE-1 IHC expression with the translocation X;18 in fluorescence in situ hybridization (FISH) for diagnosing SS. However, due to poor t(X;18) FISH signal, this paper describes troubleshooting plans for FISH analysis that were carried out in determining positive signals for t(X;18). We conducted a cross sectional study using 27 archived formalin-fixed paraffin embedded tissue blocks of synovial sarcoma, which was diagnosed in Hospital Universiti Sains Malaysia from year 1999 to July 2017. Histology assesment was performed to identify SS morphology subtypes. All samples were stained for TLE-1 by immunohistochemistry (IHC) and correlate morphology subtypes. In addition, (FISH) study were performed on formalin-fixed paraffin embedded tissue sections using break-apart SYT probe ,which hybridized to target the breakpoint gene. Troubleshooting for FISH were carried out in obtaining positive t(X;18) signal in SS cells From IHC analysis, 74.1% (20 cases) of synovial sarcoma showed positive nuclear immunoreactivity to TLE-1. Strong nuclear immunoreactivity (3+) was 48.% and moderate nuclear immunoreactivity (2+) was 25.9%. Seven cases (25.9%) were negative to TLE-1 (score 0 or 1+). The cases with no nuclear staining (0) was 18.5% and weak nuclear immunoreactivity (1+) was 7.4%. TLE-1 expression was not statistically significant with tumour morphology subtypes. Due to poor t(X;18) FISH signal, several troubleshooting plans were carried out i.e. pretreatment step, enzyme digestion and hybridization step, which the steps are known to be very sensitive to temperature, time and pH. TLE-1 is a useful marker in diagnosing SS and to distinguish from its histological mimickers. The final diagnosis of SS is only by pathologist eyes, as we still rely on morphology and IHC interpretation. The presence of agreement between TLE-1 IHC and its gold standard test (FISH) is a ticket for not to proceed with the later, which is more laborious and expensive. However, failure of signal detection due to technical and wrong methodology, we unable to proof the agreement.
- PublicationProseal laryngeal mask airway versus endotracheal tube for delivering positive pressure ventilation during lap aroscopic surgery.(2007-05)The purpose of our study is to assess whether the new Proseal Laryngeal Mask airway (PLMA) can be a suitable alternative to the standard use of Endotracheal Tube (ETT) as an airway adjunct to deliver positive pressure ventilation during laparoscopic surgeries. We compared haemodynamic changes (by measuring heart rates, systolic blood pressures, diastolic blood pressures and mean arterial pressures at different time intervals) throughout the surgery, the quality of airway maintenance by measuring Sp02 and ETC02 and recorded intra operative as well as post operative complications related to use of both airway devices. We performed a prospective single blinded study on 64 patients undergoing laparoscopic surgical procedures. These patients were randomized using block randomization and divided into two groups; PLMA and ETT group. Both groups have 32 patients. After standardized induction of anaesthesia, PLMA or ETT was inserted and the patient was connected to ventilator that delivered positive pressure ventilation at set tidal volume and rate. Anaesthesia was maintained with Nitrous oxide, Oxygen and Isoflurane. Both airway devices were removed at the end of surgery with the patients fully awake. The haemodynamic changes were recorded at different time intervals, together with Sp02 and ETC02 changes. The incidences of intra operative complications (coughing, regurgitation, bronchospasm, desaturation and gas leaking) were recorded if present. The presence of blood upon airway device removal that indicates airway trauma was also recorded. Then we recorded post operative complications if present (persistent cough, vomiting and sore throat). We found that there were no statistical differences in HR changes measured at different time intervals between PLMA and ETT. However there were statistically significant decrease in systolic blood pressures and mean arterial pressures for PLMA group at 1 minute, 5 minute, 10 minute and 15 minute post intubation. For diastolic blood pressures, the lower values in PLMA group were only significant at 10 and 15 minutes post intubations. Comparing Sp02 and ETC02 monitoring, generally there were no significant statistical differences for both groups studied. Our findings on intra operative complications were that both groups have no statistical difference in the incidence of coughing, regurgitation, desaturation, bronchospasm and gas leaking. For presence of blood upon airway devices removal, we found no statistical difference between PLMA and ETT groups. The incidence of post operative persistent coughing and vomiting were also found to be statistically insignificant for both groups, however incidence of post operative sore throat was significantly higher in ETT group compared to PLMA with p value ofO.OOl. Therefore we concluded that for laparoscopic surgery with positive pressure ventilation, PLMA is a suitable alternative to standard ETI use and may offer advantages in terms of haemodynamic changes, with lower incidences or no statistically significant peri operative complications related to its use.
- PublicationAntimetastatic and immunomodulatory potential of strobilanthes crispus subfraction and its specific major components in experimental breast cancer model(2018-02)Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‗Pecah kaca‘ or ‗Jin batu‘ which have demonstrated potent anticancer effects in both in vitro and in vivo models. However, there is paucity of information on the inhibition of metastasis and immune activation potentials of S. crispus as part of its anticancer mechanism. Thus in this study, the antimetastatic and immunomodulatory activities of S. crispus subfraction (SCS) and its specific major constituents, lutein and β-sitosterol were investigated, particularly to unravel the underlying mechanisms involved, using in vitro and in vivo models of breast cancer. In the in vitro study, murine and human breast cancer cell (BCC) lines, 4T1 and MDA-MB-231, respectively, were treated with SCS and investigated for antimetastatic activity using cell proliferation, wound-healing and invasion assays. The results showed that SCS induced moderate cell growth arrest after 24h (100 μg/ml) and 48h (75 μg/ml) treatment of 4T1 and MDA-MB-231 BCC lines compared to the untreated control cells. SCS moderately inhibited metastasis independent of its cytotoxic effects due to inhibition of migration and invasion of cancer cells below the half maximal inhibitory concentration compared to the untreated control cells. In addition, flow cytometry was carried out to evaluate the expression of cell surface immune markers (CIITA, MHC I and MHC II) in 4T1 cells treated with SCS (50 μg/ml) for 24h, and the results showed considerable expression of all the tested proteins compared to the isotype control. The in vivo study evaluated the antimetastatic and immunomodulatory activities of SCS, lutein and β-sitosterol in 4T1-induced mouse mammary carcinoma model. Beginning from 2 mm tumor size, five each (n = 5) from tumor bearing mice (TM) were administered SCS (TM-S group), lutein (TM-L group) and β-sitosterol (TM-β group) by oral gavage daily for 30 days, and the response to treatment was assessed based on the outcome of the tumor growth parameters, as well as hematological and histomorphological analyses. The results demonstrated a few complete regression of primary tumor (20%) in TM-S (100 mg/kg/day) and partial tumor regression in the rest of TM-S, TM-L and TM-β (50 mg/kg/day), and without secondary tumor formation or tumor-associated lesions in the major organs of treated groups compared to the TM group. The tumor regression was linked to blockage of tumor evasion of the immune system and activation of T cell-mediated tumor destruction, as indicated by significant increase in CD4, CD8, CD45RO, CIITA, IL2, MHCI and MHCII expression with concomitant decrease in CD68 expression compared to the TM group. In addition, SCS relatively modulated tumor cell migration, invasion and angiogenesis, through downregulation of MMP9, MUC1 and VEGF in comparison with the TM group. Additionally, TM-S showed significant increase in E-cadherin expression with resultant decrease in N-cadherin, vimentin and Twist expression SCS. In general, these results demonstrate for the first time that SCS induced antimetastasis and immune system activation effects as part of its anticancer mechanism in 4T1-induced mouse mammary tumor model, and SCS-related bioactive constituents, especially lutein could perhaps contribute significantly to the anticancer potential of SCS.
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