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Fulltext The in vivo rodent micronucleus assay of Kacip Fatimah (Labisia pumila) extract

Zaizuhana S, Puteri J Noor MB, Noral'ashikin Y, Muhammad H, Rohana AB, Zakiah I

Trop Biomed, 2006 Dec;23(2):214-9.
PMID: 17322824 MyJurnal

Kacip Fatimah also known as Labisia pumila (Myrsinaceae), is a traditional herbal medicine with a long history in the Malay community. It has been used by many generations of Malay women to induce and facilitate childbirth as well as a post-partum medicine. We tested the genotoxic potential of Kacip Fatimah in bone marrow cells obtained from Sprague-Dawley rats using micronuclei formation as the toxicological endpoints. Five groups of five male rats each were administered orally for two consecutive days with doses of 100, 700 and 2000 mg/kg body weight of Kacip Fatimah extract dissolved in distilled water. Micronucleus preparation was obtained from bone marrow cells of the animals following standard protocols. No statistically significant increase in micronucleated polychromatic erythrocytes (MNPCEs) was observed at any dose level and sacrifice/harvest time point (24, 48 and 72h). However, a significant decrease in polychromatic erythrocytes/normochromatic erythrocytes (PCE:NCE) ratio was observed from the highest dose level (2000 mg/kg of body weight) at 48h harvest time point. In this study, we investigated the effect of Kacip Fatimah on mammalian bone marrow cells using micronuclei formation to assess the genotoxicity of the herb.
Nonclinical Features in Predictive Modeling of Cardiovascular Diseases: A Machine Learning Approach

Sajid MR, Muhammad N, Zakaria R, Shahbaz A, Bukhari SAC, Kadry S, et al.

Interdiscip Sci, 2021 Jun;13(2):201-211.
PMID: 33675528 DOI: 10.1007/s12539-021-00423-w

BACKGROUND: In the broader healthcare domain, the prediction bears more value than an explanation considering the cost of delays in its services. There are various risk prediction models for cardiovascular diseases (CVDs) in the literature for early risk assessment. However, the substantial increase in CVDs-related mortality is challenging global health systems, especially in developing countries. This situation allows researchers to improve CVDs prediction models using new features and risk computing methods. This study aims to assess nonclinical features that can be easily available in any healthcare systems, in predicting CVDs using advanced and flexible machine learning (ML) algorithms.
METHODS: A gender-matched case-control study was conducted in the largest public sector cardiac hospital of Pakistan, and the data of 460 subjects were collected. The dataset comprised of eight nonclinical features. Four supervised ML algorithms were used to train and test the models to predict the CVDs status by considering traditional logistic regression (LR) as the baseline model. The models were validated through the train-test split (70:30) and tenfold cross-validation approaches.
RESULTS: Random forest (RF), a nonlinear ML algorithm, performed better than other ML algorithms and LR. The area under the curve (AUC) of RF was 0.851 and 0.853 in the train-test split and tenfold cross-validation approach, respectively. The nonclinical features yielded an admissible accuracy (minimum 71%) through the LR and ML models, exhibiting its predictive capability in risk estimation.
CONCLUSION: The satisfactory performance of nonclinical features reveals that these features and flexible computational methodologies can reinforce the existing risk prediction models for better healthcare services.
HLA-A and breast cancer in West Peninsular Malaysia

Leong PP, Muhammad R, Ibrahim N, Cheong SK, Seow HF

Med Oncol, 2011 Mar;28(1):51-6.
PMID: 20069393 DOI: 10.1007/s12032-009-9414-6

Breast cancer is the most common malignancy among females in Malaysia. Attempts have been made to investigate the association between breast cancer and human leukocyte antigen (HLA) types. However, data from those previous studies are highly variable. The aim of this study is to investigate the association between HLA-A types and clinicopathological factors in breast cancer. The frequencies of HLA-A type in 59 female patients with infiltrating ductal of the breast were determined by polymerase chain reaction method. HLA-A2/A30 and A2/A31 haplotype (5.1%; P = 0.045) as well as HLA-A30 (5.1%, P = 0.045) and A31 (6.8%; P = 0.020) allele were significant higher in the patients than controls (0%). HLA-A24 allele was negatively related to lymph node metastasis (r = -0.316; P = 0.021) whereas, A26 (r = -0.430; P = 0.001) and A36 (r = -0.430; P = 0.001) alleles were negatively correlated to distant metastasis in breast cancer. Negative correlations between HLA-A26/A36 (r = -0.430; P = 0.001), A2/A11 (r = -0.276; P = 0.044), A24/A34 (r = -0.430; P = 0.001) haplotypes and distant metastasis were identified. Interestingly, Her2 expression in breast carcinoma was negatively correlated to A11/24 haplotypes (r = -0.294; P = 0.034) but positively correlated to homozygous HLA-A24 (r = 0.396; P = 0.040). In conclusion, HLA-A2, -A30 and A31 were associated with breast cancer.
Effects of diabetes self-management education program on lowering blood glucose level, stress, and quality of life among females with type 2 diabetes mellitus in Thailand

Nooseisai M, Viwattanakulvanid P, Kumar R, Viriyautsahakul N, Muhammad Baloch G, Somrongthong R

Prim Health Care Res Dev, 2021 Sep 15;22:e46.
PMID: 34521493 DOI: 10.1017/S1463423621000505

AIM: The aim of this study is to assess the effect of diabetes self-management education (DSME) on lowering blood glucose level, stress, and quality of life (QoL) among female patients with type 2 diabetes mellitus (T2DM) in Thailand.
BACKGROUND: The burden of noncommunicable diseases has increased globally, and it has negatively affected the QoL of diabetic patients.
METHODS: A quasi-experimental study was conducted by including 77 T2DM patients selected from 2 public health centers in Thailand. The respondents were randomly selected 38 in control group and 39 in intervention group. Pretested, piloted, and validated tool were used during this study. Knowledge on blood glucose level, stress, and QoL was measured at baseline and then compared to end line after 3 months of the intervention. The effects of intervention were estimated by regression coefficient of intervention on blood glucose level and QoL. The study was ethically approved by the Chulalongkorn University, Thailand.
FINDINGS: Baseline characteristics of both the groups were similar before the start of the intervention and there were no significant differences observed in age, education, blood sugar monitoring behavior, medical checkup, knowledge, self-care, stress, and hemoglobin HbA1c (>0.05). However, blood HbA1c, stress level, and QoL among the T2DM patients had significant changes (<0.05) after the intervention. The control group was remained same and there was no statistically significant difference reported (>0.05).
CONCLUSIONS: The study concluded that the designed intervention of DSME has proved effective in lowering the blood sugar level, HbA1c level, stress level, and improved QoL among T2DM patients during this limited period of time. Hence, policy-makers can replicate this intervention for diabetic patients in a similar context.
Optoelectronic properties of naphtho[2, 1-b:6, 5-b']difuran derivatives for photovoltaic application: a computational study

Chaudhry AR, Ahmed R, Irfan A, Mohamad M, Muhammad S, Ul Haq B, et al.

J Mol Model, 2016 Oct;22(10):248.
PMID: 27683259

Some important optoelectronic properties of naphtho[2,1-b:6,5-b']difuran (DPNDF) and its two derivatives have been limelighted by applying the density functional theory (DFT). Due to their low cost, high stability and earth abundance, the DPNDF and its derivatives are considered as potential organic semiconductor materials for their optoelectronics applications. Highly proficient derivatives are obtained systematically by attaching -CN (cyanide) to DPNDF at various sites. Our calculations indicate that DPNDF has a wide and direct band gap with an energy gap of 3.157 eV. Whereas the band gaps of its derivatives are found to be decreased by 88 meV for derivative "a" and 300 meV for derivative "b" as a consequence of p orbitals present in C and N atoms in derivative structures. The narrowing of the energy gap and density of states for the derivatives of DPNDF in the present investigation suggest that energy gap can be engineered for desirable optoelectronic applications via derivatives designing. Furthermore, their obtained results for optical parameters such as the dielectric and conductivity functions, reflectivity, refractive index, and the extinction coefficients endorses their aptness for optoelectronic applications. Graphical Abstract Real part of dielectric function for derivative "b".
Fulltext Nationwide Survey of Knowledge and Health Beliefs regarding Human Papillomavirus among HPV-Vaccinated Female Students in Malaysia

Wong LP, Raja Muhammad Yusoff RN, Edib Z, Sam IC, Zimet GD

PLoS One, 2016 09 22;11(9):e0163156.
PMID: 27656876 DOI: 10.1371/journal.pone.0163156

The National HPV Immunization Programme, which offers free human papillomavirus (HPV) vaccines to teenaged female students, was launched in Malaysia in 2010. HPV vaccination paired with adequate knowledge about HPV infection provides the best protection against cervical cancer. To identify the level of knowledge and the health beliefs towards HPV and the HPV vaccine among HPV-vaccinated female students in Malaysia. A nationwide cross-sectional survey among 14 years old female students who had received three doses of the HPV vaccine was conducted in 32 randomly selected schools from 13 states and 3 federal territories in Malaysia between February 2013 and April 2013. Among 2482 respondents, knowledge about HPV infection and the HPV vaccine was extremely poor. The mean total knowledge score was only 3.56 (SD ± 1.76), out of a possible score of 10. The majority of respondents were unaware that vaccinating boys with HPV can help protect girls against HPV infection (91.6%), HPV cannot be cured (81.6%) and that HPV is a sexually transmitted infection (70.3%). Most of the respondents had the misconception that only females get HPV (95.1%), and that the HPV vaccine eliminates the need for Pap smear tests (68.3%). Most respondents (91.6%) believed that they would not get an HPV infection. Almost half of the respondents (42.9%) held the misconception that HPV infection could not lead to serious illness. Findings revealed poor knowledge about both HPV and the HPV vaccine, low perceived susceptibility to HPV infection and misinformation about HPV infection among HPV-vaccinated girls. Therefore, it is essential to increase the knowledge and awareness of health risks regarding HPV infection among teenaged girls who have received the HPV vaccine.
Fabrication of pristine Mn2O3 and Ag-Mn2O3 composite thin films by AACVD for photoelectrochemical water splitting

Naeem R, Ali Ehsan M, Yahya R, Sohail M, Khaledi H, Mazhar M

Dalton Trans, 2016 Oct 14;45(38):14928-39.
PMID: 27549401 DOI: 10.1039/c6dt02656g

Pristine Mn2O3 and Ag-Mn2O3 composite thin films have been developed on fluorine doped tin oxide (FTO) coated glass substrates at 450 °C by aerosol assisted chemical vapor deposition (AACVD) using a methanol solution of a 1 : 2 mixture of acetatoargentate(i), Ag(CH3COO), and a newly synthesized manganese complex, [Mn(dmae)2(TFA)4] (1) (dmae = N,N-dimethylaminoethanolate, TFA = trifluoroacetate). The phase purity and stoichiometric composition of the films were investigated by X-ray diffraction (XRD) and Raman spectroscopy techniques. Energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analyses revealed a Ag to Mn ratio of 1 : 2 and further confirmed the uniform dispersion of Ag nanoparticles into the Mn2O3 structure. Optical studies showed a direct band gap of 2.0 eV for the pristine Mn2O3 film that was lowered to 1.8 eV for Ag-Mn2O3 due to the plasmonic interaction of Ag with Mn2O3. The Ag-Mn2O3 composite film displayed enhanced photocatalytic activity in photoelectrochemical (PEC) water splitting and yielded a photocurrent of 3 mA cm(-2) at 0.7 V versus Ag/AgCl which was 1.6 times higher than a pristine Mn2O3 film alone, under AM 1.5 G illumination (100 mW cm(-2)). The high PEC efficiency is mainly due to the plasmonic effect of Ag nanoparticles, which enhances the visible light absorption, efficient electron-hole separation and high carrier mobility of the Ag-Mn2O3 photoelectrode. The charge carrier density of Ag-Mn2O3 is two times higher than the pristine Mn2O3 as calculated by the Mott-Schottky plot. Based on the PEC studies a mechanism is proposed to elucidate the high activity of Ag-Mn2O3 in PEC water splitting.
Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies

Taha M, Ismail NH, Ali M, Rashid U, Imran S, Uddin N, et al.

Bioorg Chem, 2017 04;71:192-200.
PMID: 28228228 DOI: 10.1016/j.bioorg.2017.02.005

The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies

Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.

Bioorg Chem, 2017 06;72:89-101.
PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014

Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
Fulltext Physical and psychosocial impacts of pregnancy on adolescents and their coping strategies: a descriptive study in Kuala Lumpur, Malaysia

Su XV, Muhammad NA, Tan PS, Tan KTM, Tohid H, Omar K

Malaysian Journal of Public Health Medicine, 2014;14(3):0-0.
MyJurnal

Teenage pregnancy carries serious impacts on adolescent health. This study aimed to examine the effects of pregnancy on adolescents and to explore how they cope with the problems they faced during the pregnancy. It involved 26 adolescents residing in a government shelter home in Kuala Lumpur. A self-administered questionnaire containing a mixture of open- and closed-ended questions was used. Among physical (sleeping problem and self-care problem), psychological (emotional difficulties and low self-efficacy) and social (stigma and discrimination, financial difficulty, friendship problem and school dropout) problems, emotional difficulties were the most common problems, whereas stigma and discrimination was the least common. Young adolescents aged less than 16 years old were significantly associated with poor self-care (p=0.01). To cope with their problems, the adolescents generally used avoidance, withdrawal, and social support, particularly from parents and peers. Doctors were the least popular among all. In conclusion, holistic and individualised care is needed. Strategies to reduce emotional problem experienced by pregnant adolescents should be implemented. The available healthcare services for teenage pregnancy should also be promoted.
Fulltext The Effect of Microwave Roasting Over the Thermooxidative Degradation of Perah Seed Oil During Heating

Li KS, Ali MA, Muhammad II, Othman NH, Noor AM

J Oleo Sci, 2018 May 01;67(5):497-505.
PMID: 29628486 DOI: 10.5650/jos.ess17203

The impact of microwave roasting on the thermooxidative degradation of perah seed oil (PSO) was evaluated during heating at a frying temperature (170°C). The roasting resulted significantly lower increment of the values of oxidative indices such as free acidity, peroxide value, p-anisidine, total oxidation (TOTOX), specific extinctions and thiobarbituric acid in oils during heating. The colour L* (lightness) value dropped gradually as the heating time increased up to 12 h, whereas a*(redness) and b* (yellowness) tended to increase. The viscosity and total polar compound in roasted PSO was lower as compared to that in unroasted one at each heating times. The tocol retention was also high in roasted samples throughout the heating period. The relative contents of polyunsaturated fatty acids (PUFAs) were decreased to 94.42% and saturated fatty acids (SFAs) were increased to 110.20% in unroasted sample, after 12 h of heating. On the other hand, in 3 min roasted samples, the relative contents of PUFAs were decreased to 98.08% and of SFAs were increased to 103.41% after 12 h of heating. Outcome from analyses showed that microwave roasting reduced the oxidative deteriorations of PSO during heating.
Economic Impact of Pneumococcal Protein-D Conjugate Vaccine (PHiD-CV) on the Malaysian National Immunization Programme

Aljunid S, Maimaiti N, Ahmed Z, Muhammad Nur A, Md Isa Z, Azmi S, et al.

Value Health Reg Issues, 2014 May;3:146-155.
PMID: 29702920 DOI: 10.1016/j.vhri.2014.04.008

OBJECTIVE: To assess the cost-effectiveness of introducing pneumococcal polysaccharide and nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in the National Immunization Programme of Malaysia. This study compared introducing PHiD-CV (10 valent vaccine) with current no vaccination, as well as against the alternative 13-valent pneumococcal conjugate vaccine (PCV13).

METHODS: A lifetime Markov cohort model was adapted using national estimates of disease burden, outcomes of pneumococcal disease, and treatment costs of disease manifestations including pneumonia, acute otitis media, septicemia, and meningitis for a hypothetical birth cohort of 550,000 infants. Clinical information was obtained by review of medical records from four public hospitals in Malaysia from the year 2008 to 2009. Inpatient cost from the four study hospitals was obtained from a diagnostic-related group-based costing system. Outpatient cost was estimated using clinical pathways developed by an expert panel. The perspective assessed was that of the Ministry of Health, Malaysia.

RESULTS: The estimated disease incidence was 1.2, 3.7, 70, and 6.9 per 100,000 population for meningitis, bacteremia, pneumonia, and acute otitis media, respectively. The Markov model predicted medical costs of Malaysian ringgit (RM) 4.86 billion (US $1.51 billion) in the absence of vaccination. Vaccination with PHiD-CV would be highly cost-effective against no vaccination at RM30,290 (US $7,407) per quality-adjusted life-year gained. On comparing PHiD-CV with PCV13, it was found that PHiD-CV dominates PCV13, with 179 quality-adjusted life-years gained while saving RM35 million (US $10.87 million).

CONCLUSIONS: It is cost-effective to incorporate pneumococcal vaccination in the National Immunization Programme of Malaysia. Our model suggests that PHiD-CV would be more cost saving than PCV13 from the perspective of the Ministry of Health of Malaysia.

Study site: UKM Medical Centre, Hospital Kuala Lumpur, Hospital
Alor Setar, and Hospital Queen Elizabeth, Kota Kinabalu
Fulltext Integrated Characterization of MicroRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma

Mohamad Yusof A, Jamal R, Muhammad R, Abdullah Suhaimi SN, Mohamed Rose I, Saidin S, et al.

Front Endocrinol (Lausanne), 2018;9:158.
PMID: 29713312 DOI: 10.3389/fendo.2018.00158

The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA-genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value
High angiotensin-I converting enzyme (ACE) inhibitory activity of Alcalase-digested green soybean (Glycine max) hydrolysates

Hanafi MA, Hashim SN, Chay SY, Ebrahimpour A, Zarei M, Muhammad K, et al.

Food Res Int, 2018 04;106:589-597.
PMID: 29579964 DOI: 10.1016/j.foodres.2018.01.030

As a protein-rich, underutilized crop, green soybean could be exploited to produce hydrolysates containing angiotensin-I converting enzyme (ACE) inhibitory peptides. Defatted green soybean was hydrolyzed using four different food-grade proteases (Alcalase, Papain, Flavourzyme and Bromelain) and their ACE inhibitory activities were evaluated. The Alcalase-generated green soybean hydrolysate showed the highest ACE inhibitory activity (IC50: 0.14 mg/mL at 6 h hydrolysis time) followed by Papain (IC50: 0.20 mg/mL at 5 h hydrolysis time), Bromelain (IC50: 0.36 mg/mL at 6 h hydrolysis time) and Flavourzyme (IC50: 1.14 mg/mL at 6 h hydrolysis time) hydrolysates. The Alcalase-generated hydrolysate was profiled based on its hydrophobicity and isoelectric point using reversed phase high performance liquid chromatography (RP-HPLC) and isoelectric point focusing (IEF) fractionators. The Alcalase-generated green soybean hydrolysate comprising of peptides EAQRLLF, PSLRSYLAE, PDRSIHGRQLAE, FITAFR and RGQVLS, revealed the highest ACE inhibitory activity of 94.19%, 99.31%, 92.92%, 101.51% and 90.40%, respectively, while their IC50 values were 878 μM, 532 μM, 1552 μM, 1342 μM and 993 μM, respectively. It can be concluded that Alcalase-digested green soybean hydrolysates could be exploited as a source of peptides to be incorporated into functional foods with antihypertensive activity.
Fracture risk prediction in post-menopausal women with osteopenia and osteoporosis: preliminary findings

Nik Mohd Hatta NNK, Lokman M, Said N M, Daud A, Ibrahim M, Sharifudin MA, et al.

Enferm Clin, 2018 Feb;28 Suppl 1:232-235.
PMID: 29650194 DOI: 10.1016/S1130-8621(18)30074-3

OBJECTIVE: The study aims to identify the risk of obtaining a fracture among post-menopausal women with osteopenia and osteoporosis.

METHOD: This work was a cross-sectional study involving a purposive sample of 87 post-menopausal women who attended the orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan, Kuantan. The data were entered into the WHO fracture risk assessment tool (FRAX®) to predict major fracture and risk for hip fracture in 10 years' time.

RESULTS: The mean age of the respondents was 61.6 years (SD=7.9). Among the respondents, 50.6% had osteopenia and nearly half (48.3%) had osteoporosis. The mean number of menopausal years of the respondents was 11.9 (SD=8.5), ranging between 1 and 44 years. The FRAX findings indicated 9.7% major osteoporotic fracture probability and 3.5% hip fracture probability, which were denoted as high risk. A Pearson correlation coefficient was computed to assess the relationship between menopausal years and the FRAX major osteoporotic fracture probability. A significant positive correlation was found between the two, but the correlation was weak (r=0.581, n=87, p < 0.001).

CONCLUSIONS: The present findings indicate that menopausal years have a positive correlation with the risk of obtaining a fracture.

Study site: orthopedic and menopause clinics of Hospital Tengku Ampuan Afzan, Kuantan.
Gene Expression Profiling associated with Hepatoxicity in Pregnant Rats treated with Ubi Gadong (Dioscorea hispida) Extract

Faradianna Lokman E, Muhammad H, Awang N, Hasyima Omar M, Mansor F, Saparuddin F

Int J Biomed Sci, 2017 Mar;13(1):26-34.
PMID: 28533734

Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called 'ubi gadong'. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.
Fulltext Treating an infected transcatheter pacemaker system via percutaneous extraction

Koay A, Khelae S, Wei KK, Muhammad Z, Mohd Ali R, Omar R

HeartRhythm Case Rep, 2016 Jul;2(4):360-362.
PMID: 28491710 DOI: 10.1016/j.hrcr.2016.04.006
Fulltext Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies

Ashraf Z, Rafiq M, Nadeem H, Hassan M, Afzal S, Waseem M, et al.

PLoS One, 2017;12(5):e0178069.
PMID: 28542395 DOI: 10.1371/journal.pone.0178069

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver-Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.
Fulltext Synthesis, in-Vitro and in Silico Studies of Azo-Based Calix[4]arenes as Antibacterial Agent and Neuraminidase Inhibitor: A New Look Into an Old Scaffold

Ali Y, Muhamad Bunnori N, Susanti D, Muhammad Alhassan A, Abd Hamid S

Front Chem, 2018;6:210.
PMID: 29946538 DOI: 10.3389/fchem.2018.00210

Calixarene derivatives are reported as potential therapeutic agents. Azo derivatives of calixarenes have not been given much consideration to explore their biomedical applications. In the present study, some azo-based derivatives of calix[4]arene were synthesized and characterized and their antibacterial and antiviral potentials were studied. The mono azo products of sulphanilamide, sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against bacterial strains with minimum inhibition concentration values ranging from 0.97 to 62.5 μg/mL. For mono azo products, the diazotized salt was applied as a limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3 (molar ratio) helped in partial substitution. Molecular docking was performed to see the interaction of the designed compounds with two bacterial and one viral (neuraminidase) receptor. Some of the derivatives showed good interaction with the active site of bacterial and neuraminidase enzymes through hydrogen, hydrophobic and pi-pi interactions, and could inhibit the activity of the selected enzymes.
Genomic evaluations of Wolbachia and mtDNA in the population of coconut hispine beetle, Brontispa longissima (Coleoptera: Chrysomelidae)

Ali H, Muhammad A, Bala NS, Wang G, Chen Z, Peng Z, et al.

Mol Phylogenet Evol, 2018 10;127:1000-1009.
PMID: 29981933 DOI: 10.1016/j.ympev.2018.07.003

Wolbachia pipientis is a diverse, ubiquitous and most prevalent intracellular bacterial group of alpha-Proteobacteria that is concerned with many biological processes in arthropods. The coconut hispine beetle (CHB), Brontispa longissima (Gestro) is an economically important pest of palm cultivation worldwide. In the present study, we comprehensively surveyed the Wolbachia-infection prevalence and mitochondrial DNA (mtDNA) polymorphism in CHB from five different geographical locations, including China's Mainland and Taiwan, Vietnam, Thailand, Malaysia and Indonesia. A total of 540 sequences were screened in this study through three different genes, i.e., cytochrome oxidase subunit I (COI), Wolbachia outer surface protein (wsp) and multilocus sequencing type (MLST) genes. The COI genetic divergence ranges from 0.08% to 0.67%, and likewise, a significant genetic diversity (π = 0.00082; P = 0.049) was noted within and between all analyzed samples. In the meantime, ten different haplotypes (H) were characterized (haplotype diversity = 0.4379) from 21 different locations, and among them, H6 (46 individuals) have shown a maximum number of population clusters than others. Subsequently, Wolbachia-prevalence results indicated that all tested specimens of CHB were found positive (100%), which suggested that CHB was naturally infected with Wolbachia. Wolbachia sequence results (wsp gene) revealed a high level of nucleotide diversity (π = 0.00047) under Tajima's D test (P = 0.049). Meanwhile, the same trend of nucleotide diversity (π = 0.00041) was observed in Wolbachia concatenated MLST locus. Furthermore, phylogenetic analysis (wsp and concatenated MLST genes) revealed that all collected samples of CHB attributed to same Wolbachia B-supergroup. Our results strongly suggest that Wolbachia bacteria and mtDNA were highly concordant with each other and Wolbachia can affect the genetic structure and diversity within the CHB populations.

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