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Fulltext Arterial stiffness during acute and recovery phases of children with rheumatic fever

Ibrahim NN, Jaafar H, Rasool AH, Wong AR

Med J Malaysia, 2016 02;71(1):23-5.
PMID: 27130739

Acute rheumatic fever (ARF) is associated with systemic inflammation and arterial stiffness during the acute stage. It has not been reported if arterial stiffness remains after recovery. The aim of this study was to determine the arterial stiffness during acute stage and 6 months after recovery from ARF. Arterial stiffness was assessed by carotid femoral pulse wave velocity (PWV) in 23 ARF patients during the acute stage of ARF and 6 months later. Simultaneously, erythrocyte sedimentation rate (ESR) and other anthropometric measurements were taken during both stages. There was a significant reduction in PWV; 6.5 (6.0, 7.45) m/s to 5.9 (5.38, 6.48) m/s, p=0.003 6 months after the acute stage of ARF. Similarly, ESR was also significantly reduced from 92.0 (37.5, 110.50) mm/hr to 7.0 (5.0, 16.0) mm/hr, p=0.001. In conclusion, arterial stiffness improved 6 months after the acute stage with routine aspirin treatment; this correlates well with the reduction in systemic inflammation.
Fulltext Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats

Ilmie MU, Jaafar H, Mansor SM, Abdullah JM

Front Neurosci, 2015;9:189.
PMID: 26136645 DOI: 10.3389/fnins.2015.00189

Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.
Effects of Malaysian thermal spring water as adjunct therapy for mild to moderate acne vulgaris - a prospective, randomised, controlled, split face study

Faisal UA, Jamil A, Jaafar H, Aqma WS, Arumugam M

Med J Malaysia, 2024 Mar;79(2):157-164.
PMID: 38553920

INTRODUCTION: Acne is a common skin disease with a high psychosocial burden, affecting mostly adolescents and youth worldwide. Management of acne is often challenged by cutaneous side effects that leads to therapeutic intolerance, poor compliance and impaired efficacy.
MATERIALS AND METHODS: This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only.
RESULTS: Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment.
CONCLUSION: TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.
Fulltext Optimization of Flavonoid Extraction from Red and Brown Rice Bran and Evaluation of the Antioxidant Properties

Ghasemzadeh A, Baghdadi A, Z E Jaafar H, Swamy MK, Megat Wahab PE

Molecules, 2018 Jul 26;23(8).
PMID: 30049990 DOI: 10.3390/molecules23081863

Recently, the quality-by-design concept has been widely implemented in the optimization of pharmaceutical processes to improve batch-to-batch consistency. As flavonoid compounds in pigmented rice bran may provide natural antioxidants, extraction of flavonoid components from red and brown rice bran was optimized using central composite design (CCD) and response surface methodology (RSM). Among the solvents tested, ethanol was most efficient for extracting flavonoids from rice bran. The examined parameters were temperature, solvent percentage, extraction time, and solvent-to-solid ratio. The highest total flavonoid content (TFC) in red rice bran was predicted as 958.14 mg quercetin equivalents (QE)/100 g dry matter (DM) at 58.5 °C, 71.5% (v/v), 36.2 min, and 7.94 mL/g, respectively, whereas the highest TFC in brown rice bran was predicted as 782.52 mg QE/100 g DM at 56.7 °C, 74.4% (v/v), 36.9 min, and 7.18 mL/g, respectively. Verification experiment results under these optimized conditions showed that the TFC values for red and brown rice bran were 962.38 and 788.21 mg QE/100 g DM, respectively. No significant differences were observed between the predicted and experimental TFC values, indicating that the developed models are accurate. Analysis of the extracts showed that apigenin and p-coumaric acid are abundant in red and brown rice bran. Further, red rice bran with its higher flavonoid content exhibited higher nitric oxide and 2,2-diphenyl-1-picrylhydrazyl scavenging activities (EC50 values of 41.3 and 33.6 μg/mL, respectively) than brown rice bran. In this study, an extraction process for flavonoid compounds from red and brown rice bran was successfully optimized. The accuracy of the developed models indicated that the approach is applicable to larger-scale extraction processes.
Fulltext The differential roles of caspase family members in mediating PF4-induced breast cancer apoptosis

Tengku Din TADAA, Abdul Jalal MI, Seeni A, Shamsuddin S, Jaafar H

Malays J Pathol, 2018 Dec;40(3):303-312.
PMID: 30580361

INTRODUCTION: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer.

MATERIALS AND METHODS: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 μg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining.

RESULTS: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups.

CONCLUSION: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.
Fulltext Enhancing Photocurrent Performance Based on Photoanode Thickness and Surface Plasmon Resonance Using Ag-TiO2 Nanocomposites in Dye-Sensitized Solar Cells

Lokman MQ, Shafie S, Shaban S, Ahmad F, Jaafar H, Mohd Rosnan R, et al.

Materials (Basel), 2019 Jun 30;12(13).
PMID: 31262020 DOI: 10.3390/ma12132111

This study investigated the different thicknesses of TiO2 photoanode films and the effect of surface plasmon resonance (SPR) of Ag-TiO2 nanocomposites on the current-voltage (I-V) performance of dye-sensitized solar cells (DSSC). The TiO2 layer was deposited using the doctor blade technique and the thickness of the TiO2 films was controlled by using a different number of Scotch tape layers. The silver nanoparticles (AgNP) were synthesised using a chemical reduction method and the concentration of sodium citrate as a reducing agent was varied from 4 to 12 mM to study the effect of citrate ion on the size of the nanoparticles. Ag-TiO2 nanopowder was prepared by adding pure anatase TiO2 powder into AgNP colloidal solution. The mixture was left to dry for 24 h to obtain Ag-TiO2 powder for paste preparation. The three-layer Scotch tape, with thickness of 14.38 µm, achieved a high efficiency of 4.14%. This results showed that three layers was the optimal thickness to improve dye loading and to reduce the charge recombination rate. As for the Ag-TiO2 nanocomposites, 10 mM of AgNP, with a mean diameter of 65.23 nm and high efficiency of 6.92%, proved that SPR can enhance the absorption capability of dye and improve the photon-to-electron generation.
Fulltext Mangosteen (Garcinia mangostana) flesh supplementation attenuates biochemical and morphological changes in the liver and kidney of high fat diet-induced obese rats

Muhamad Adyab NS, Rahmat A, Abdul Kadir NAA, Jaafar H, Shukri R, Ramli NS

BMC Complement Altern Med, 2019 Dec 02;19(1):344.
PMID: 31791316 DOI: 10.1186/s12906-019-2764-5

BACKGROUND: Mangosteen is a native fruit from Southeast Asia. It is rich in phenolic compounds such as xanthones, anthocyanins and phenolic acids. Mangosteen pericarp extract showed inhibitory activity towards pancreatic lipase and may have potential use for obesity treatment. However, there is limited study on the beneficial effects of mangosteen flesh against obesity. This study aimed to investigate the effects of Garcinia mangostana flesh (GMF) on biochemical and morphological changes in the liver and kidney of high-fat diet-induced obese rats.
METHODS: Forty healthy Sprague-Dawley rats were randomised into five groups (n = 8) with four groups were fed with high-fat diet (HFD) for 10 weeks and a control group was fed with rat chow diet. Supplementation with GMF in obese rats was continued for 7 weeks starting from week 10th after the initiation of HFD at different doses (200 mg/kg, 400 mg/kg and 600 mg/kg). The positive and negative control rats were given distilled water via oral gavage. Plasma lipid profile, antioxidant enzymes and pro-inflammatory markers were determined using commercial kits. Liver and kidney structure were defined by histology.
RESULTS: The rats fed with HFD for 10 weeks increased plasma LDL-cholesterol, reduced plasma glutathione peroxidase level and had significantly higher body weight compared to normal control rats (p
Fulltext Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Jaffar NFN, Muhammad Sakri MS, Jaafar H, Wan Abdul Rahman WF, Tengku Din TADA

Asian Pac J Cancer Prev, 2020 Oct 01;21(10):2919-2925.
PMID: 33112549 DOI: 10.31557/APJCP.2020.21.10.2919

OBJECTIVE: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib.
METHODS: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis.
RESULTS: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring.
CONCLUSION: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.
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Fulltext Phenazine from Pseudomonas aeruginosa UPMP3 induced the host resistance in oil palm (Elaeis guineensis Jacq.)-Ganoderma boninense pathosystem

Parvin W, Govender N, Othman R, Jaafar H, Rahman M, Wong MY

Sci Rep, 2020 Sep 24;10(1):15621.
PMID: 32973199 DOI: 10.1038/s41598-020-72156-7

Pseudomonas aeruginosa developed its biocontrol agent property through the production of antifungal derivatives, with the phenazine among them. In this study, the applications of crude phenazine synthesized by Pseudomonas aeruginosa UPMP3 and hexaconazole were comparatively evaluated for their effectiveness to suppress basal stem rot infection in artificially G. boninense-challenged oil palm seedlings. A glasshouse experiment under the randomized completely block design was set with the following treatments: non-inoculated seedlings, G. boninense inoculated seedlings, G. boninense inoculated seedlings with 1 mg/ml phenazine application, G. boninense inoculated seedlings with 2 mg/ml phenazine application and G. boninense inoculated seedlings with 0.048 mg/ml hexaconazole application. Seedlings were screened for disease parameters and plant vigour traits (plant height, plant fresh weight, root fresh, and dry weight, stem diameter, and total chlorophyll) at 1-to-4 month post-inoculation (mpi). The application of 2 mg/ml phenazine significantly reduced disease severity (DS) at 44% in comparison to fungicide application (DS = 67%). Plant vigour improved from 1 to 4 mpi and the rate of disease reduction in seedlings with phenazine application (2 mg/ml) was twofold greater than hexaconazole. At 4, 6 and 8 wpi, an up-regulation of chitinase and β-1,3 glucanase genes in seedlings treated with phenazine suggests the involvement of induced resistance in G. boninense-oil palm pathosystem.
Investigating the performance of an amplitude-independent algorithm for detecting the hand muscle activity of stroke survivors

Hameed HK, Wan Hasan WZ, Shafie S, Ahmad SA, Jaafar H, Inche Mat LN

J Med Eng Technol, 2020 Apr;44(3):139-148.
PMID: 32396756 DOI: 10.1080/03091902.2020.1753838

To make robotic hand devices controlled by surface electromyography (sEMG) signals feasible and practical tools for assisting patients with hand impairments, the problems that prevent these devices from being widely used have to be overcome. The most significant problem is the involuntary amplitude variation of the sEMG signals due to the movement of electrodes during forearm motion. Moreover, for patients who have had a stroke or another neurological disease, the muscle activity of the impaired hand is weak and has a low signal-to-noise ratio (SNR). Thus, muscle activity detection methods intended for controlling robotic hand devices should not depend mainly on the amplitude characteristics of the sEMG signal in the detection process, and they need to be more reliable for sEMG signals that have a low SNR. Since amplitude-independent muscle activity detection methods meet these requirements, this paper investigates the performance of such a method on people who have had a stroke in terms of the detection of weak muscle activity and resistance to false alarms caused by the involuntary amplitude variation of sEMG signals; these two parameters are very important for achieving the reliable control of robotic hand devices intended for people with disabilities. A comparison between the performance of an amplitude-independent muscle activity detection algorithm and three amplitude-dependent algorithms was conducted by using sEMG signals recorded from six hemiparesis stroke survivors and from six healthy subjects. The results showed that the amplitude-independent algorithm performed better in terms of detecting weak muscle activity and resisting false alarms.
Fulltext Microvessel density and vascular endothelial growth factor receptors in breast carcinoma under the influence of rapamycin and platelet factor 4

Muhammad Sakri MS, Abdul Rahman WFW, Tengku Din TADA, Idris FM, Jaafar H

Indian J Pathol Microbiol, 2020 4 23;63(2):205-209.
PMID: 32317516 DOI: 10.4103/IJPM.IJPM_496_19

Background: Vascular endothelial growth factor receptors (VEGFRs) are major endothelial growth factor receptors that influence the growth of a tumor. Microvessel density.
(: MVD) is the quantification method of various aspects of tumor vasculature that indicates angiogenic activity. This study aims to analyze the correlation between MVD to the expression of VEGFRs on breast cancer tissue.
Materials and Method: A total of 60 N-methyl-N-nitrosourea (MNU)-induced breast carcinomas in rats were suppressed by using antiangiogenic drugs. The rats were then sacrificed, and the tumor was fixed in 10% formalin, paraffin embedded, and immunohistochemistry stained using VEGFRs and CD34.
Result: One-way ANOVA test showed a significant difference in all markers that have been used (P < 0.05) on MNU-breast tumor treated with rapamycin (M= 90.1664, SD= 7.4487), PF4 (M= 93.7946, SD= 7.1303) and rapamycin + PF4 (M= 93.6990, SD= 1.8432). We obtained a significant reduction of MVD count on breast carcinoma for rapamycin group (M= 25.6786, SD= 9.7075) and rapamycin + PF4 group (M= 30.5250, SD= 13.6928) while PF4 group (M=47.7985, SD=4.8892) showed slightly increase compared to control (M= 45.1875, SD= 4.4786). There was a moderately strong, positive correlation between angiogenic markers; Flt-1 (r= 0.544, n=60, P < 0.005) and Flt-4 (r= 0.555, n= 60, P < 0.005) while Flk-1 (r= 0.797, n= 60, P < 0.005) showed a strong, positive correlation with MVD.
Conclusion: MVD was strongly correlated to the VEGFRs expression on breast carcinoma.
Fulltext Malignant rhabdoid tumour of the brain

Abdullah JM, Rahman ZA, Ariff AR, Jaafar H, Phang KS

Singapore Med J, 2004 Jun;45(6):286-8.
PMID: 15181525

Rhabdoid tumour is a rare childhood tumour with poor prognosis. We report a 13-month-old Malay girl suffering from this tumour that was located at the left fronto-temporo-parietal region of the brain. Computed tomography showed a large irregular enhancing mass that caused obstructive hydrocephalus. The tumour did not reduce in size after three operations and finally the patient succumbed to the disease four months after diagnosis.
Fulltext What We Know about the Molecular Genetics of Central Nervous System (CNS) Tumours in Malaysia

Sulong S, Yusoff AA, Zainuddin N, Abdullah JM, Pannatil JG, Jaafar H, et al.

Malays J Med Sci, 2004 Jan;11(1):37-43.
PMID: 22977358 MyJurnal

The new millennium has been regarded as a genomic era. A lot of researchers and pathologists are beginning to understand the scientific basis of molecular genetics and relates with the progression of the diseases. Central nervous system (CNS) tumours are among the most rapidly fatal of all cancers. It has been proposed that the progression of malignant tumours may result from multi-step of genetic alterations, including activation of oncogenes, inactivation of tumour suppressor genes and also the presence of certain molecular marker such as telomerase activity. In this paper, we review some recent data from the literature, including our own studies, on the molecular genetics analysis in CNS tumours. Our studies have shown that two types of tumour suppressor genes, p53 and PTEN were involved in the development of these tumours but not in p16 gene among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase activity also has been detected in various types of CNS tumours. Thus, it is important to assemble all data which related to this study and may provide as a vital information in a new approach to neuro-oncology studies in Malaysia.
PF4-Induced apoptosis in breast cancer in vivo study: The role of the caspases family

Din TA, Seeni A, Yusoff MS, Shamsuddin S, Jaafar H

Pathology, 2016 Feb;48 Suppl 1:S122.
PMID: 27772839 DOI: 10.1016/j.pathol.2015.12.324
Fulltext Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

Tang SP, Kuttulebbai Nainamohamed Salam S, Jaafar H, Gan SH, Muzaimi M, Sulaiman SA

Oxid Med Cell Longev, 2017;2017:4605782.
PMID: 28127418 DOI: 10.1155/2017/4605782

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
Fulltext The Relationship between Internet Addiction, Internet Gaming and Anxiety among Medical Students in a Malaysian Public University during COVID-19 Pandemic

Ismail N, Tajjudin AI, Jaafar H, Nik Jaafar NR, Baharudin A, Ibrahim N

Int J Environ Res Public Health, 2021 11 12;18(22).
PMID: 34831627 DOI: 10.3390/ijerph182211870

The internet has become an important medium for learning and communication during the COVID-19 pandemic, particularly for university students. Nevertheless, an increase in internet usage could predispose people to internet addiction (IA) and internet gaming (IG). Equally, there is concern that anxiety levels have increased during the pandemic. The aim of this study is to determine the prevalence of IA and IG, and their associations with anxiety among medical students during the pandemic. Data were collected during the second wave of the "Conditional Movement Control Order" (CMCO) in Malaysia between 12 November and 10 December 2020. A total of 237 students participated through proportionate stratified random sampling in this cross-sectional study. They completed a set of online questionnaires which consisted of a sociodemographic profile, the Malay version of the internet addiction test (MVIAT), the Malay version of the internet gaming disorder-short form (IGDS9-SF) and the Malay version of the depression, anxiety and stress scale (DASS-21). The prevalence of IA and internet gaming disorder (IGD) were 83.5% and 2.5%, respectively. A multiple logistic regression showed that those in pre-clinical years had a greater risk of anxiety than those in clinical years [(AOR) = 2.49, p-value 0.01, 95% CI = 1.22-5.07]. In contrast, those who scored high on IA were protected against anxiety [AOR = 0.100, p-value 0.03, 95% CI = 0.01-0.76)]. In conclusion, IA was highly prevalent during the COVID-19 pandemic and its high usage might serve as a protective factor against anxiety among the medical students in this study sample.
Fulltext Evaluation of Cyclooxygenase-2 and p53 Expression in Pterygium Tissue Following Preoperative Intralesional Ranibizumab Injection

Omar AR, Ibrahim M, Jaafar H, Siti-Azrin AH, Zunaina E

Front Med (Lausanne), 2021;8:733523.
PMID: 35004714 DOI: 10.3389/fmed.2021.733523

Introduction: Overexpression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and p53 are the postulated aetiopathogenesis in pterygium. VEGF is responsible for the induction of COX-2 expression, whereas p53 plays an important role in the regulation of VEGF. This study aimed to evaluate the immunohistochemistry of COX-2 and p53 expressions from excised pterygium tissue from patients who received intralesional ranibizumab (anti-VEGF) injection 2 weeks prior to pterygium surgery. Materials and Methods: An interventional comparative study involving patients presenting with primary pterygium was conducted between September 2015 and November 2017. The patients were randomized into either the intervention or control group. Patients in the intervention group were injected with intralesional ranibizumab (0.5 mg/0.05 ml) 2 weeks prior to surgery. Both groups underwent pterygium excision followed by conjunctival autograft. Immunohistochemistry staining was performed to evaluate COX-2 and p53 expressions in the excised pterygium tissue. Results: A total of 50 patients (25 in both the intervention and control groups) were recruited. There were 34 (68%) patients with grade III pterygium and 16 (32%) patients with grade IV pterygium. There was statistically significant difference in reduction of COX-2 expression in the epithelial layer [84.0% (95% CI: 63.9, 95.5)] (p = 0.007) and stromal layer [84.0% (95% CI: 63.9, 95.5)] (p < 0.001) between intervention and control groups. There was no significant difference in the reduction of p53 expression between the two groups. Conclusion: This study demonstrated the possible use of intralesional anti-VEGF treatment prior to pterygium excision as a potential future modality of adjunctive therapy for pterygium surgery.
Fulltext Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma

Muhammad Sakri MS, Tengku Din TADA, Jaafar H, Gopalan V, Wan Abdul Rahman WF

Int J Immunopathol Pharmacol, 2022;36:20587384211059673.
PMID: 35037503 DOI: 10.1177/20587384211059673

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.
Fulltext IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells

Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H

BMC Neurosci, 2014;15:91.
PMID: 25047045 DOI: 10.1186/1471-2202-15-91

There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.
Normabaric Hyperoxia Treatment Improved Locomotor Activity of C57BL/6J Mice through Enhancing Dopamine Genes Following Fluid-Percussion Injury in Striatum

Muthuraju S, Taha S, Pati S, Rafique M, Jaafar H, Abdullah JM

Int J Biomed Sci, 2013 Dec;9(4):194-204.
PMID: 24711754

Closed traumatic brain injury (CTBI) leads to increase mortality rates in developing countries. However, a sustainable therapeutic approach has not been established yet. Therefore, the present study was designed to evaluate the impact of normabaric hyperoxia treatment (NBOT) on striatum associated Locomotor Activity (LA) in IntelliCage after Fluid-Percussion Injury (FPI). Animals were divided in four groups: Group I control (n=24), Group II sham (n=24), Group III FPI (n=24) and Group IV FPI with NBOT (n=24). Animals were habituated in IntelliCage for 4 days following transponder implanted in mice neck region on day 5. Then the LA of all groups was assessed 6hr daily for 5 days before inducing FPI. On day 6, cannula was implanted on the striatum, on day 7 FPI was performed in Group III (kept in normal environment) and IV (immediately exposed to NBOT for 3 hr). LA (in terms of number of visits in all four corners) was assessed 6 hr at days 1, 7, 14, 21 and 28 following FPI. After the animals were sacrificed to study the neuronal damage, dopamine receptors and transporters expression in striatum. The results suggested that the LA of FPI impaired mice as compared to the control and sham showed less number of visits in all four corners in IntelliCage. Morphological results revealed that FPI induced neuronal damage as compared to sham and control. Dopamine receptors and transporters were down regulated in the FPI group as compared to the control. Immediate exposure to NBOT improved LA in terms of increased number of visits in all four corners, reduced number of cell death and improved receptor expression as compared to FPI. In conclusion, NBOT exposure could improve the LA of mice following FPI through prevention of neuronal damage, improved dopamine receptors and transporters.

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