1.The synthetic molecules YK51 and YK73 attenuate replication of dengue virus serotype 2
Gan, C.S. ; Yusof, R. ; Othman, S.
Tropical Biomedicine 2017;34(2):270-283
Dengue virus infection has been posing alarming economic and social burden on
affected nations. It is estimated that 50-100 million dengue infections occur annually with
over 2.5 billion people at risk for endemic transmission. In the effort to develop effective
antiviral agents, we previously reported potential antiviral activities from selected array of
natural products and compounds against dengue virus serotype 2 (DV2). In this study, we
report the synthesis of two efficacious novel compounds, YK51 and YK73, and their activities
against DV2 replication. Both compounds were chemically synthesised from nicotinic acid
using a modified method for the synthesis of dihydropyridine. The products were tested with
cell-based assays against DV2 followed by a serine protease assay. As a result, both YK51 and
YK73 exhibited intriguing antiviral properties with EC50 of 3.2 and 2.4 µM, respectively. In
addition, YK51 and YK73 were found to attenuate the synthesis of intracellular viral RNA and
protect the switching of non-classic mechanism of protein translation. These compounds
demonstrated inhibitory properties toward the activity of DV2 serine protease in a dose
dependent manner. These findings demonstrate that both YK51 and YK73 serve as DV2 serine
protease inhibitors that abrogate viral RNA synthesis and translation. Further investigation
on these compounds to corroborate its therapeutic properties towards dengue is warranted.
2.Soil-transmitted helminth infections among malaria patients determined by microscopy and real-time PCR methods at two district hospitals in Sarawak, Malaysia
Othman, N. ; Basuni, M. ; Miswan, N. ; Noordin, R.
Tropical Biomedicine 2015;32(4):710-716
Malaria is still endemic in Sarawak and Sabah. Numerous studies have indicated
that patients with malaria are commonly co-infected with helminthes particularly in endemic
regions. The aim of this study was to investigate the incidence of soil-transmitted helminth
(STH) infection among malaria patients using microscopy and multiplex real-time PCR at two
district hospitals in Sarawak. A total of 94 patients who were clinically-suspected to have
malaria were confirmed to be infected by both microscopy and multiplex real-time PCR. By
the molecular method, 23.4%, 74.5% and 2.1% of the samples were positive for Plasmodium
falciparum, P. vivax and mixed P. falciparum and P. vivax, respectively. Among the malaria
patients, 48.9% were found to be co-infected with STHs. In comparison, microscopic
examinations showed that 6.4% of the malaria patients were infected with STHs. From the
real-time PCR positive samples, 31.9% had single helminth infections while 17% had mixed
infections. In conclusion, this study showed that almost half of the malaria patients at the
two Sarawak hospitals were co-infected with helminth. Future studies should be specifically
designed to determine if there is any correlation between the two infections in terms of
incidence and intensity.
3.Prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinoma: A histochemical study.
Lauren Nieuwenhuizen ; Mohd Khairy Khalil ; Venkatesh R. Naik ; Nor Hayati Othman
Malaysian Journal of Medical Sciences 2007;14(1):56-61
To determine the prevalence of goblet cell metaplasia in endocervical and endometrial adenocarcinomas by histochemial staining and to investigate the most sensitive histochemical staining method to detect this metaplasia, a total of 90 tissue blocks representing 30 non-neoplastic cervix, 30 non-neoplastic endometrium, 30 endocervical and endometrial adenocarcinoma cases were obtained for histochemical staining with Toluidine Blue (TB), Methylene Blue (MB), Mucicarmine (MUC), Periodic Acid Schiff before and after Diastase digestion (PAS, PAS-D), Alcian Blue pH 2.5 (AB), and Periodic Acid Schiff after Alcian Blue pH 2.5 (PAB). The cases were blinded and evaluated by a pathologist [NHO] for the presence of goblet cell metaplasia, the amount of goblet cells present and the histochemical differentiation of the goblet cells compared with its surrounding glandular epithelium. Goblet cell metaplasia was present in 2 out of 30 cases in non-neoplastic cervix, 0 out of 30 cases in non-neoplastic endometrium, 7 out of 15 cases in endocervical adenocarcinoma and in 2 out of 15 cases in endometrial
adenocarcinoma. Relatively few goblet cells were seen in endometrial adenocarcinoma, few to moderate amounts were seen in endocervical adenocarcinoma and relatively more goblet cells were seen in non-neoplastic cervix. The differentiation of the goblet cells with its surrounding glandular epithelium was moderate to strong in non-neoplastic cervix and endocervical adenocarcinoma, while the differentiation in endometrial adenocarcinoma was weak to moderate. The various staining methods showed differences in presence, amount anddifferentiation of the goblet cells. Goblet cell metaplasia of the reproductive organs is not as rare as previously reported. There was no statistical difference in presence, amount and differentiation of goblet cells according to the various cases. The must optimum staining methods for staining goblet cells in non-neoplastic cervix, endocervical adenocarcinoma and endometrial adenocarcinoma were PAS, PASD and AB.
4.Optimal protein extraction methods from diverse sample types for protein profiling by using Two-Dimensional Electrophoresis (2DE)
Tan, A.A. ; Azman, S.N. ; Abdul Rani, N.R. ; Kua, B.C. ; Sasidharan, S. ; Kiew, L.V. ; Othman, N. ; Noordin, R. ; Chen, Y.*
Tropical Biomedicine 2011;28(3):620-629
There is a great diversity of protein samples types and origins, therefore the
optimal procedure for each sample type must be determined empirically. In order to obtain a
reproducible and complete sample presentation which view as many proteins as possible on
the desired 2DE gel, it is critical to perform additional sample preparation steps to improve
the quality of the final results, yet without selectively losing the proteins. To address this, we
developed a general method that is suitable for diverse sample types based on phenolchloroform
extraction method (represented by TRI reagent). This method was found to yield
good results when used to analyze human breast cancer cell line (MCF-7), Vibrio cholerae,
Cryptocaryon irritans cyst and liver abscess fat tissue. These types represent cell line,
bacteria, parasite cyst and pus respectively. For each type of samples, several attempts were
made to methodically compare protein isolation methods using TRI-reagent Kit, EasyBlue Kit,
PRO-PREPTM Protein Extraction Solution and lysis buffer. The most useful protocol allows the
extraction and separation of a wide diversity of protein samples that is reproducible among
repeated experiments. Our results demonstrated that the modified TRI-reagent Kit had the
highest protein yield as well as the greatest number of total proteins spots count for all type
of samples. Distinctive differences in spot patterns were also observed in the 2DE gel of
different extraction methods used for each type of sample.
6.Cytotoxicity and scanning electron microscopy study of gentamycin-coated HA effect on biofilm.
Au LF ; Othman F ; Mustaffa R ; Vidyadaran S ; Rahmat A ; Besar I ; Akim AM ; Khan MA ; Saidi M ; Shamsudin MN ; Froemming GA ; Ishak AK
The Medical Journal of Malaysia 2008;63 Suppl A():16-17
Biofilms are adherent, multi-layered colonies of bacteria that are typically more resistant to the host immune response and routine antibiotic therapy. HA biomaterial comprises of a single-phased hydroxyapatite scaffold with interconnected pore structure. The device is designed as osteoconductive space filler to be gently packed into bony voids or gaps following tooth extraction or any surgical procedure. Gentamycin-coated biomaterial (locally made hydroxyapatite) was evaluated to reduce or eradicate the biofilm on the implant materials. The results indicated that the HA coated with gentamycin was biocompatible to human osteoblast cell line and the biofilm has been reduced after being treated with different concentrations of gentamycin-coated hydroxyapatite (HA).
7.Psychotherapy For Prison Populations: A Review
Mohammad Rahim Kamaluddin ; Linthini Gannetion ; Maria Magdalina anak Dennis Janting ; Nur Deanna Rosli ; R Nurul Najwa Baharuddin ; Geshina Ayu Mat Saat ; Kamsiah Kamin ; Azizah Othman
ASEAN Journal of Psychiatry 2018;19(1):1-
Introduction: Psychotherapy is a form of treatment intervention targeting problematical human behaviour, emotion, and cognition using various psychological techniques and approaches. In Malaysia, the application of psychotherapy in ameliorating criminality among forensic populations is developing and evidence shows that some therapies like Cognitive-Behavioural Therapy and Reality Therapy have been practiced in many correctional institutions. Objective: This paper aims to review the role of psychotherapy for help in correctional settings as a means to ameliorate criminal behaviour and reduce recidivism rates. Method: An archival research was utilised, where articles and books regardless of the year of publication from different countries, including Malaysia were examined. Several keywords were used for the purpose of retrieval of related articles. Results and Discussion: Three different approaches of psychotherapies, i.e. Behavioural Therapy, Cognitive Therapy and Cognitive-Behavioural Therapy and their principles and effectiveness in rehabilitating the forensic populations were elaborated in this review. The principle behind the effectiveness of the psychotherapy was different, and this influences the choice of treatment that should be used in dealing with the forensic populations. Conclusion: Â Forensic populations have rights to obtain treatment, and the choice of therapy has to be relevant within the context of cost-effectiveness to ensure optimum effectiveness in ameliorating criminal tendencies. Â
8.Adipose tissue-derived mesenchymal stem cells reduce endometriosis cellular proliferation through their anti-inflammatory effects
Fatma Y. MELIGY ; Dalia A. ELGAMAL ; Lobna A. ABDELZAHER ; Maha Y. KHASHBAH ; Mohamed A. EL-MOKHTAR ; Ayat A. SAYED ; Abeer M. REFAIY ; Essam R. OTHMAN
Clinical and Experimental Reproductive Medicine 2021;48(4):322-336
Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role. Methods: Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats’ peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1β, IL-10, and transforming growth factor β expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status. Results: The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines. Conclusion: Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.
9.Phytochemical screening, cytotoxic and antimicrobial activities of Limonium socotranum and Peperomia blanda extracts
Al-Madhagi, W.M. ; Hashim, N.M. ; Ali, N.A.A. ; Othman, R.
Tropical Biomedicine 2019;36(1):11-21
Limonium socotranum and Peperomia blanda are used in ethnomedicine to treat
several diseases, such as infection, cancer, and inflammation. P. blanda (family: Piperaceae)
is from the genus Peperomia, and mostly found in Madagascar, Yemen, USA to South America,
while L. socotranum (family: Plumbaginaceae) from the genus Limonium and this species
is found only on Socotra Island, Yemen. These plants have attracted great interest in recent
years because of their phytochemical contents. Consequently, the current study is aimed to
investigate the phytochemical constituents, the cytotoxic and antimicrobial activities of L.
socotranum (leaves and stem) and P. blanda extracts. Successive extraction had been
performed which resulted in nine crude extracts. Phytochemical screening of the extracts
was then conducted using qualitative chemical analysis. The antimicrobial activity of the
plant extracts was determined using the well diffusion method against eleven selected
pathogenic microbes and the minimum inhibitory concentrations (MIC) were measured. The
cytotoxic activities of the plant extracts against MCF-7 and HepG2 cell lines were investigated
using sulforhodamine B assay. It was noted that methanol leaves extract from L. socotranum
exhibited higher antibacterial activity against Micrococcus luteus (MIC 15.6 μg/mL),
Staphylococcus aureus (MIC 125 μg/mL) and Pseudomonas aeruginosa (MIC 125 μg/mL),
than stem parts, while petroleum ether extract displayed stronger antifungal activity, with
MIC of 125 μg/mL. On the other hand, petroleum ether extract of P. blanda was effective
against Gram-positive bacteria and exhibited moderate antifungal activity. Petroleum ether
extract of P. blanda displayed cytotoxic activity against MCF-7 cells, with an IC50 of 4.60 ±
0.02 μg/mL, while the methanol extracts showed higher activity against the HepG2 cell line,
with an IC50 of 13.90 ± 0.14 μg/mL. Phytochemical findings confirmed the presence of
flavonoids, alkaloids and terpenoids. The promising obtained results suggest the potential
use of these plants in cancer and antimicrobial therapies.
10.Dengue protease inhibition activity of selected Malaysian medicinal herbs
Salleh, H.M. ; Chong, S.-L. ; Othman, R. ; Hazni, H. ; Ahmad, K. ; Mohd Yusof, M.Y.Z. ; Fauzi, N.W. ; Wahab, H.A. ; Liew, S.Y. ; Awang, K.
Tropical Biomedicine 2019;36(2):357-366
Dengue fever is one of major health problem around the world including Malaysia.
It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes
aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes
(DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various
Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops
aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited
potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of
Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with
IC50 value of 0.30 ± 0.16 μg/mL.