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Morphological and phenotypical characteristics of human osteoblasts after short-term space mission

Kapitonova MY, Kuznetsov SL, Salim N, Othman S, Kamauzaman TM, Ali AM, et al.

Bull. Exp. Biol. Med., 2014 Jan;156(3):393-8.
PMID: 24771384 DOI: 10.1007/s10517-014-2357-8

Morphological and phenotypical signs of cultured readaptation osteoblasts were studied after a short-term space mission. The ultrastructure and phenotype of human osteoblasts after Soyuz TMA-11 space flight (2007) were evaluated by scanning electron microscopy, laser confocal microscopy, and ELISA. The morphofunctional changes in cell cultures persisted after 12 passages. Osteoblasts retained the drastic changes in their shape and size, contour deformation, disorganization of the microtubular network, redistribution of organelles and specialized structures of the plasmalemma in comparison with the ground control cells. On the other hand, the expression of osteoprotegerin and osteocalcin (bone metabolism markers) increased; the expression of bone resorption markers ICAM-1 and IL-6 also increased, while the expression of VCAM-1 decreased. Hence, space flight led to the development of persistent shifts in cultured osteoblasts indicating injuries to the cytoskeleton and the phenotype changes, indicating modulation of bone metabolism biomarkers.
High-intensity interval training induced PGC-1∝ and AdipoR1 gene expressions and improved insulin sensitivity in obese individuals

Asilah Za'don NH, Amirul Farhana MK, Farhanim I, Sharifah Izwan TO, Appukutty M, Salim N, et al.

Med J Malaysia, 2019 12;74(6):461-467.
PMID: 31929469

INTRODUCTION: High-intensity interval training (HIIT) has been found to improve cardiometabolic health outcome as compared to moderate-intensity continuous exercise. However, there is still limited data on the benefits of HIIT on the expression of regulatory proteins that are linked to skeletal muscle metabolism and insulin sensitivity in obese adults. This study investigated the effects of HIIT intervention on expressions of peroxisome proliferatoractivated receptor-γ coactivator 1-∝ (PGC-1∝) and adiponectin receptor-1 (AdipoR1), insulin sensitivity (HOMAIR index), and body composition in overweight/obese individuals.
METHODS: Fifty overweight/obese individuals aged 22-29 years were assigned to either no-exercise control (n=25) or HIIT (n=25) group. The HIIT group underwent a 12-week intervention, three days/week, with intensity of 65-80% of age-based maximum heart rate. Anthropometric measurements, homeostatic model of insulin resistance (HOMA-IR) and gene expression analysis were conducted at baseline and post intervention.
RESULTS: Significant time-by-group interactions (p<0.001) were found for body weight, BMI, waist circumference and body fat percentage. The HIIT group had lower body weight (2.3%, p<0.001), BMI (2.7%, p<0.001), waist circumference (2.4%, p<0.001) and body fat percentage (4.3%, p<0.001) post intervention. Compared to baseline, expressions of PGC-1∝ and AdipoR1 were increased by approximately three-fold (p=0.019) and two-fold (p=0.003) respectively, along with improved insulin sensitivity (33%, p=0.019) in the HIIT group.
CONCLUSION: Findings suggest that HIIT possibly improved insulin sensitivity through modulation of PGC-1∝ and AdipoR1. This study also showed that improved metabolic responses can occur despite modest reduction in body weight in overweight/obese individuals undergoing HIIT intervention.
Fulltext Gastroprotective effect of Berberis vulgaris on ethanol-induced gastric mucosal injury: Histopathological evaluations

Kapitonova M, Gupalo S, Alyautdin R, Ibrahim IAA, Salim N, Ahmad A, et al.

Avicenna J Phytomed, 2022;12(1):30-41.
PMID: 35145893 DOI: 10.22038/AJP.2021.18113

OBJECTIVE: Modern treatment of peptic ulcers includes antibacterial and gastroprotective medications. However, current anti-ulcer drugs possess severe side effects. Therefore, all attempts to find new effective medications free from side effects are justified. Though Berberis vulgaris is a medicinal plant commonly used for the treatment of numerous disorders, gastroprotective effect of its leaf extract was not investigated before.
MATERIALS AND METHODS: Gastric ulcer was modelled in Sprague-Dawley rats after treatment with B. vulgaris leaf extract containing 0.07% of alkaloids, 0.48% of flavonoids and 8.05% of tanning substances, 10 or 50 mg of dry extract/kg, changes in the stomach mucosa were assessed semi-quantitatively, and the gastric wall was evaluated for prostaglandin E2 level using ELISA and assessed histologically by calculation of the lesion index.
RESULTS: B. vulgaris leaf extract at the dose of 50 mg/kg reduced the macroscopic ulcer score and the microscopic lesion index, increased prostaglandin E2 concentration in the gastric wall significantly higher than atropine and B. vulgaris leaf extract 10 mg/kg.
CONCLUSION: The gastroprotective effect of the high dose of B. vulgaris leaf extract may be due to stimulation of prostaglandin E2 secretion in the stomach, and anti-oxidative and anti-inflammatory properties of polyphenolic complex of flavonoids and tannins present in the leaves of this plant.
Fulltext Intelligent bar chart plagiarism detection in documents

Al-Dabbagh MM, Salim N, Rehman A, Alkawaz MH, Saba T, Al-Rodhaan M, et al.

ScientificWorldJournal, 2014;2014:612787.
PMID: 25309952 DOI: 10.1155/2014/612787

This paper presents a novel features mining approach from documents that could not be mined via optical character recognition (OCR). By identifying the intimate relationship between the text and graphical components, the proposed technique pulls out the Start, End, and Exact values for each bar. Furthermore, the word 2-gram and Euclidean distance methods are used to accurately detect and determine plagiarism in bar charts.
Fulltext Alteration of cell cytoskeleton and functions of cell recovery of normal human osteoblast cells caused by factors associated with real space flight

Kapitonova MY, Salim N, Othman S, Muhd Kamauzaman TM, Ali AM, Nawawi HM, et al.

Malays J Pathol, 2013 Dec;35(2):153-63.
PMID: 24362479 MyJurnal

Experiments involving short-term space flight have shown an adverse effect on the physiology, morphology and functions of cells investigated. The causes for this effect on cells are: microgravity, temperature fluctuations, mechanical stress, hypergravity, nutrient restriction and others. However, the extent to which these adverse effects can be repaired by short-term space flown cells when recultured in conditions of normal gravity remains unclear. Therefore this study aimed to investigate the effect of short-term spaceflight on cytoskeleton distribution and recovery of cell functions of normal human osteoblast cells. The ultrastructure was evaluated using ESEM. Fluorescent staining was done using Hoechst, Mito Tracker CMXRos and Tubulin Tracker Green for cytoskeleton. Gene expression of cell functions was quantified using qPCR. As a result, recovered cells did not show any apoptotic markers when compared with control. Tubulin volume density (p<0.001) was decreased significantly when compared to control, while mitochondria volume density was insignificantly elevated. Gene expression for IL-6 (p<0.05) and sVCAM-1 (p<0.001) was significantly decreased while alkaline phosphatase (p<0.001), osteocalcin and sICAM (p<0.05) were significantly increased in the recovered cells compared to the control ones. The changes in gene and protein expression of collagen 1A, osteonectin, osteoprotegerin and beta-actin, caused by short-term spaceflight, were statistically not significant. These data indicate that short term space flight causes morphological changes in osteoblast cells which are consistent with hypertrophy, reduced cell differentiation and increased release of monocyte attracting proteins. The long-term effect of these changes on bone density and remodeling requires more detailed studies.
Arrhythmia recognition and classification using combined linear and nonlinear features of ECG signals

Elhaj FA, Salim N, Harris AR, Swee TT, Ahmed T

Comput Methods Programs Biomed, 2016 Apr;127:52-63.
PMID: 27000289 DOI: 10.1016/j.cmpb.2015.12.024

Arrhythmia is a cardiac condition caused by abnormal electrical activity of the heart, and an electrocardiogram (ECG) is the non-invasive method used to detect arrhythmias or heart abnormalities. Due to the presence of noise, the non-stationary nature of the ECG signal (i.e. the changing morphology of the ECG signal with respect to time) and the irregularity of the heartbeat, physicians face difficulties in the diagnosis of arrhythmias. The computer-aided analysis of ECG results assists physicians to detect cardiovascular diseases. The development of many existing arrhythmia systems has depended on the findings from linear experiments on ECG data which achieve high performance on noise-free data. However, nonlinear experiments characterize the ECG signal more effectively sense, extract hidden information in the ECG signal, and achieve good performance under noisy conditions. This paper investigates the representation ability of linear and nonlinear features and proposes a combination of such features in order to improve the classification of ECG data. In this study, five types of beat classes of arrhythmia as recommended by the Association for Advancement of Medical Instrumentation are analyzed: non-ectopic beats (N), supra-ventricular ectopic beats (S), ventricular ectopic beats (V), fusion beats (F) and unclassifiable and paced beats (U). The characterization ability of nonlinear features such as high order statistics and cumulants and nonlinear feature reduction methods such as independent component analysis are combined with linear features, namely, the principal component analysis of discrete wavelet transform coefficients. The features are tested for their ability to differentiate different classes of data using different classifiers, namely, the support vector machine and neural network methods with tenfold cross-validation. Our proposed method is able to classify the N, S, V, F and U arrhythmia classes with high accuracy (98.91%) using a combined support vector machine and radial basis function method.
Fulltext Optimization and Characterization of Palm Oil-based Nanoemulsion Loaded with Parthenium hysterophorus Crude Extract for Natural Herbicide Formulation

Zainuddin NJ, Ashari SE, Salim N, Asib N, Omar D, Lian GEC

J Oleo Sci, 2019 Aug 01;68(8):747-757.
PMID: 31292338 DOI: 10.5650/jos.ess18209

The present study revealed the optimization of nanoemulsion containing palm oil derivatives and Parthenium hysterophorus L. crude extract (PHCE) as pre-emergence herbicide formulation against Diodia ocimifolia. The nanoemulsion formulation was prepared by high energy emulsification method, and it was optimized by mixture experimental design (MED). From the optimization process, analysis of variance (ANOVA) showed a fit quadratic polynomial model with an optimal formulation composition containing 30.91% of palm kernel oil ester (PKOE), 28.48% of mixed surfactants (Tensiofix and Tween 80, 8:2), 28.32% of water and 12.29% of PHCE. The reading of both experimental and predicted particle size in the verification experiment were acceptable with a residual standard error (RSE) was less than 2%. Under the optimal condition, the smallest particle size obtained was 140.10 nm, and the particle was shown by morphology analysis to be spherical and demonstrated good stability (no phase separation) under centrifugation and different storage conditions (25 ± 5°C and 45°C). Nanoemulsion stored for 60 days exhibits monodisperse emulsion with a slight increase of particle size. The increase in particle size over time might have contributed by Ostwald ripening phenomenon which is shown by a linear graph from Ostwald ripening rate analysis. In the in vitro germination test, P. hysterophorus nanoemulsion (PHNE) was shown to cause total inhibition of D. ocimifolia seed at lower concentration (5 g L-1) as compared to PHCE (10 g L-1). The finding of the research could potentially serve as a platform for the development of palm oil based formulation containing plant crude extract for green weed management.
Extraction, anti-tyrosinase, and antioxidant activities of the collagen hydrolysate derived from Rhopilema hispidum

Ab Aziz NA, Salim N, Zarei M, Saari N, Yusoff FM

Prep Biochem Biotechnol, 2021;51(1):44-53.
PMID: 32701046 DOI: 10.1080/10826068.2020.1789991

The study was conducted to determine anti-tyrosinase and antioxidant activities of the extracted collagen hydrolysate (CH) derived from Malaysian jellyfish, Rhopilema hispidum. Collagen was extracted using 1:1 (w:v) 0.1 M NaOH solution at temperature 25 °C for 48 hr followed by treatment of 1:2 (w:v) distilled water for another 24 hr and freeze-dried. The extracted collagen was hydrolyzed using papain at optimum temperature, pH and enzyme/substrate ratio [E/S] of 60 °C, 7.0 and 1:50, respectively. CH was found to exhibit tyrosinase inhibitory activity, DPPH radical scavenging and metal ion-chelating assays up to 64, 28, and 83%, respectively, after 8 hr of hydrolysis process. The molecular weight of CH was found <10 kDa consisting of mainly Gly (19.219%), Glu (10.428%), and Arg (8.848%). The UV-visible spectrum analysis showed a major and minor peak at 218 and 276 nm, accordingly. The FTIR spectroscopy confirmed the amide groups in CH. The SEM images demonstrated spongy and porous structure of CH. In the cytotoxicity study, CH has no cytotoxicity against mouse embryonic 3T3 fibroblast cell line with IC50 value >500 µg/ml. Results revealed that the CH generated from this study has a potential to be developed as active ingredient in cosmeceutical application.
Fulltext Modeling and optimization of nanoemulsion containing Sorafenib for cancer treatment by response surface methodology

Izadiyan Z, Basri M, Fard Masoumi HR, Abedi Karjiban R, Salim N, Shameli K

Chem Cent J, 2017;11:21.
PMID: 28293282 DOI: 10.1186/s13065-017-0248-6

The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib, which is a poorly soluble drug with no parenteral treatment. The formulation was prepared by a high energy emulsification method and optimized by response surface methodology. The effects of overhead stirring time, high shear rate, high shear time, and cycles of high-pressure homogenizer were studied in the preparation of nanoemulsion loaded with Sorafenib. Most of the particles in nanoemulsion are spherical in shape, the smallest particle size being 82.14 nm. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole reveal that the optimum formulation does not affect normal cells significantly in low drug concentrations but could remove the cancer cells. Finally, a formulation containing Sorafenib retained its properties over a period of 90 days. With characterization, the study of the formulated nanoemulsion has the potential to be used as a parenteral nanoemulsion in the treatment of cancer. Graphical abstractSchematic figure of high pressure homogenizer device.
Fulltext Enhancement of physicochemical properties of nanocolloidal carrier loaded with cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo hydrating action

Musa SH, Basri M, Fard Masoumi HR, Shamsudin N, Salim N

Int J Nanomedicine, 2017;12:2427-2441.
PMID: 28405165 DOI: 10.2147/IJN.S125302

Psoriasis is a chronic autoimmune disease that cannot be cured. It can however be controlled by various forms of treatment, including topical, systemic agents, and phototherapy. Topical treatment is the first-line treatment and favored by most physicians, as this form of therapy has more patient compliance. Introducing a nanoemulsion for transporting cyclosporine as an anti-inflammatory drug to an itchy site of skin disease would enhance the effectiveness of topical treatment for psoriasis. The addition of nutmeg and virgin coconut-oil mixture, with their unique properties, could improve cyclosporine loading and solubility. A high-shear homogenizer was used in formulating a cyclosporine-loaded nanoemulsion. A D-optimal mixture experimental design was used in the optimization of nanoemulsion compositions, in order to understand the relationships behind the effect of independent variables (oil, surfactant, xanthan gum, and water content) on physicochemical response (particle size and polydispersity index) and rheological response (viscosity and k-value). Investigation of these variables suggests two optimized formulations with specific oil (15% and 20%), surfactant (15%), xanthan gum (0.75%), and water content (67.55% and 62.55%), which possessed intended responses and good stability against separation over 3 months' storage at different temperatures. Optimized nanoemulsions of pH 4.5 were further studied with all types of stability analysis: physical stability, coalescence-rate analysis, Ostwald ripening, and freeze-thaw cycles. In vitro release proved the efficacy of nanosize emulsions in carrying cyclosporine across rat skin and a synthetic membrane that best fit the Korsmeyer-Peppas kinetic model. In vivo skin analysis towards healthy volunteers showed a significant improvement in the stratum corneum in skin hydration.
Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment

Asmawi AA, Salim N, Ngan CL, Ahmad H, Abdulmalek E, Masarudin MJ, et al.

Drug Deliv Transl Res, 2019 04;9(2):543-554.
PMID: 29691812 DOI: 10.1007/s13346-018-0526-4

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.
Fulltext Optimization of Quercetin loaded Palm Oil Ester Based Nanoemulsion Formulation for Pulmonary Delivery

Arbain NH, Salim N, Wui WT, Basri M, Rahman MBA

J Oleo Sci, 2018 Aug 01;67(8):933-940.
PMID: 30012897 DOI: 10.5650/jos.ess17253

In this research, the palm oil ester (POE)- based nanoemulsion formulation containing quercetin for pulmonary delivery was developed. The nanoemulsion formulation was prepared by high energy emulsification method and then further optimized using D-optimal mixture design. The concentration effects of the mixture of POE:ricinoleic acid (RC), ratio 1:1 (1.50-4.50 wt.%), lecithin (1.50-2.50 wt.%), Tween 80 (0.50-1.00 wt.%), glycerol (1.50-3.00 wt.%), and water (88.0-94.9 wt.%) towards the droplet size were investigated. The results showed that the optimum formulation with 1.50 wt.% POE:RC, 1.50 wt.% lecithin, 1.50 wt.% Tween 80, 1.50 wt.% glycerol and 93.90 % water was obtained. The droplet size, polydispersity index (PDI) and zeta potential of the optimized formulation were 110.3 nm, 0.290 and －37.7 mV, respectively. The formulation also exhibited good stability against storage at 4℃ for 90 days. In vitro aerosols delivery evaluation showed that the aerosols output, aerosols rate and median mass aerodynamic diameter of the optimized nanoemulsion were 99.31%, 0.19 g/min and 4.25 µm, respectively. The characterization of physical properties and efficiency for aerosols delivery results suggest that POE- based nanoemulsion containing quercetin has the potential to be used for pulmonary delivery specifically for lung cancer treatment.
Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology

Izadiyan Z, Basri M, Fard Masoumi HR, Abedi Karjiban R, Salim N, Kalantari K

Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:841-849.
PMID: 30423770 DOI: 10.1016/j.msec.2018.10.015

Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).
Fulltext Genetic diversity of Plasmodium knowlesi among human and long-tailed macaque populations in Peninsular Malaysia: The utility of microsatellite markers

Saleh Huddin A, Md Yusuf N, Razak MRMA, Ogu Salim N, Hisam S

Infect Genet Evol, 2019 11;75:103952.
PMID: 31279818 DOI: 10.1016/j.meegid.2019.103952

It has been discovered that Plasmodium knowlesi (P. knowlesi) is transmitted from macaque to man. Thus, the aim of the present study was to determine P. knowlesi genetic diversity in both human (n = 147) and long-tailed macaque (n = 26) samples from high- and low-endemicity localities. Genotyping was performed using seven neutral microsatellite loci markers. The size of the alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (HE), linkage disequilibrium (LD), and genetic differentiation (FST) were determined. In highly endemic P. knowlesi localities, the MOI for human and long-tailed macaque isolates was 1.04 and 1.15, respectively, while the Na was 11.14 and 7.86, respectively. Based on the allele frequency distribution for all loci, and with FST 
Fulltext Movie Review Summarization Using Supervised Learning and Graph-Based Ranking Algorithm

Khan A, Gul MA, Zareei M, Biswal RR, Zeb A, Naeem M, et al.

Comput Intell Neurosci, 2020;2020:7526580.
PMID: 32565772 DOI: 10.1155/2020/7526580

With the growing information on web, online movie review is becoming a significant information resource for Internet users. However, online users post thousands of movie reviews on daily basis and it is hard for them to manually summarize the reviews. Movie review mining and summarization is one of the challenging tasks in natural language processing. Therefore, an automatic approach is desirable to summarize the lengthy movie reviews, and it will allow users to quickly recognize the positive and negative aspects of a movie. This study employs a feature extraction technique called bag of words (BoW) to extract features from movie reviews and represent the reviews as a vector space model or feature vector. The next phase uses Naïve Bayes machine learning algorithm to classify the movie reviews (represented as feature vector) into positive and negative. Next, an undirected weighted graph is constructed from the pairwise semantic similarities between classified review sentences in such a way that the graph nodes represent review sentences, while the edges of graph indicate semantic similarity weight. The weighted graph-based ranking algorithm (WGRA) is applied to compute the rank score for each review sentence in the graph. Finally, the top ranked sentences (graph nodes) are chosen based on highest rank scores to produce the extractive summary. Experimental results reveal that the proposed approach is superior to other state-of-the-art approaches.
Investigation and Optimization of Hydrogel Microneedles for Transdermal Delivery of Caffeine

Chandran R, Mohd Tohit ER, Stanslas J, Salim N, Tuan Mahmood TM

Tissue Eng Part C Methods, 2022 10;28(10):545-556.
PMID: 35485888 DOI: 10.1089/ten.TEC.2022.0045

Caffeine is therapeutically effective for treating apnea, cellulite formation, and pain management. It also exhibits neuroprotective and antioxidant activities in different models of Parkinson's disease and Alzheimer's disease. However, caffeine administration in a minimally invasive and sustainable manner through the transdermal route is challenging owing to its hydrophilic nature. Therefore, this study demonstrated a transdermal delivery approach for caffeine by utilizing hydrogel microneedle (MN) as a permeation enhancer. The influence of formulation parameters such as molecular weight (MW) of PMVE/MA (polymethyl vinyl ether/maleic anhydride) copolymer and sodium bicarbonate (NaHCO3) concentration on the swelling kinetics and mechanical integrity of the hydrogel MNs was investigated. In addition, the effect of different MN application methods and needle densities of hydrogel MN on the skin insertion efficiency and penetration depth was also evaluated. The swelling degree at equilibrium percentage (% Seq) recorded for hydrogels fabricated with Gantrez S-97 (MW = 1,500,000 Da) was significantly higher than formulation with Gantrez AN-139 (MW = 1,080,000 Da). Increasing the concentration of NaHCO3 also significantly increased the % Seq. Moreover, a 100% penetration was recorded for both the applicator and combination of applicator and thumb pressure compared with only 11% for thumb pressure alone. The average diameter of micropores created by the applicator method was 62.94 μm, which was significantly lower than the combination of both applicator and thumb pressure MN application (100.53 μm). Based on histological imaging, the penetration depth of hydrogel MN increased as the MN density per array decreased. The hydrogel MN with the optimized formulation and skin insertion parameters was tested for caffeine delivery in an in vitro Franz diffusion cell setup. Approximately 2.9 mg of caffeine was delivered within 24 h, and the drug release profile was best fitted to the Korsmeyer-Peppas model, displaying Super Case II kinetics. In conclusion, a combination of thumb and impact application methods and reduced needle density improved the skin penetration efficiency of hydrogel MNs. The results also show that hydrogel MNs fabricated from 3% w/w NaHCO3 and high MW of copolymer exhibit optimum physical and swelling properties for enhanced transdermal delivery.
Fulltext Convolutional Neural Network Model Based on 2D Fingerprint for Bioactivity Prediction

Hentabli H, Bengherbia B, Saeed F, Salim N, Nafea I, Toubal A, et al.

Int J Mol Sci, 2022 Oct 30;23(21).
PMID: 36362018 DOI: 10.3390/ijms232113230

Determining and modeling the possible behaviour and actions of molecules requires investigating the basic structural features and physicochemical properties that determine their behaviour during chemical, physical, biological, and environmental processes. Computational approaches such as machine learning methods are alternatives to predicting the physiochemical properties of molecules based on their structures. However, the limited accuracy and high error rates of such predictions restrict their use. In this paper, a novel technique based on a deep learning convolutional neural network (CNN) for the prediction of chemical compounds' bioactivity is proposed and developed. The molecules are represented in the new matrix format Mol2mat, a molecular matrix representation adapted from the well-known 2D-fingerprint descriptors. To evaluate the performance of the proposed methods, a series of experiments were conducted using two standard datasets, namely the MDL Drug Data Report (MDDR) and Sutherland, datasets comprising 10 homogeneous and 14 heterogeneous activity classes. After analysing the eight fingerprints, all the probable combinations were investigated using the five best descriptors. The results showed that a combination of three fingerprints, ECFP4, EPFP4, and ECFC4, along with a CNN activity prediction process, achieved the highest performance of 98% AUC when compared to the state-of-the-art ML algorithms NaiveB, LSVM, and RBFN.
Ocular co-morbidities in patients with atopic dermatitis - a cross-sectional study from a tertiary referral hospital, Malaysia

Gan TS, Juares Rizal A, Salim NL, Lau LL, Voo SYM

Med J Malaysia, 2022 Jan;77(1):6-11.
PMID: 35086988

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing pruritic inflammatory skin disease that commonly occurs among children as well as adults. AD patients were reported to have high prevalence of ocular manifestations, which may be due to the disease nature or drug complications. This study aimed to determine the prevalence of ocular manifestations in patients with AD.
MATERIALS AND METHODS: Eighty patients who fulfilled the UK Working Party's Diagnostic Criteria for Atopic Dermatitis were included in the cross-sectional study. A standardized case report form was formulated to collect the demographic data and disease profile of the participants. AD severity was evaluated using the EASI and SCORAD score. All patients underwent a complete ophthalmological evaluation.
RESULTS: The prevalence of ocular manifestations among the patients with AD was 48.8%. Fifty-four (67.5%) patients had facial dermatitis and 37 (46.2%) showed periorbital signs. The mean AD disease duration was 10.99 ± 11.20 years. Majority of the patients had mild to moderate AD. The most frequent ocular manifestation was allergic conjunctivitis (18.75%) followed by cataract (8.75%) and ocular hypertension (8.75%). Among the patients with ocular manifestations, 27 (69.2%) patients regularly applied topical corticosteroids on the face. The use of systemic corticosteroids was seen in 19 (42.2%) patients. Prolonged AD duration was significantly associated with the development of ocular manifestations.
CONCLUSIONS: Nearly half of the patients with AD were complicated with ocular disease regardless of the AD severity, facial dermatitis and presence of periorbital signs. Long disease duration is associated with ocular manifestations, especially steroid related complications.
In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery

Arbain NH, Salim N, Masoumi HRF, Wong TW, Basri M, Abdul Rahman MB

Drug Deliv Transl Res, 2019 04;9(2):497-507.
PMID: 29541999 DOI: 10.1007/s13346-018-0509-5

Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter. The droplet size, polydispersity index, and zeta potential of the optimized formulation were 131.4 nm, 0.257, and 51.1 mV, respectively. The formulation exhibited high drug entrapment efficiency and good stability against phase separation and storage at temperature 4 °C for 3 months. It was discovered that the system had an acceptable median mass aerodynamic diameter (3.09 ± 0.05 μm) and geometric standard deviation (1.77 ± 0.03) with high fine particle fraction (90.52 ± 0.10%), percent dispersed (83.12 ± 1.29%), and percent inhaled (81.26 ± 1.28%) for deposition in deep lung. The in vitro release study demonstrated that the sustained release pattern of quercetin from naneomulsion formulation up to 48 h of about 26.75% release and it was in adherence to Korsmeyer's Peppas mechanism. The cytotoxicity study demonstrated that the optimized nanoemulsion can potentially induce cyctotoxicity towards A549 lung cancer cells without affecting the normal cells. These results of the study suggest that nanoemulsion is a potential carrier system for pulmonary delivery of molecules with low water solubility like quercetin.
MGACA-Net: a novel deep learning based multi-scale guided attention and context aggregation for localization of knee anterior cruciate ligament tears region in MRI images

Awan MJ, Mohd Rahim MS, Salim N, Nobanee H, Asif AA, Attiq MO

PeerJ Comput Sci, 2023;9:e1483.
PMID: 37547408 DOI: 10.7717/peerj-cs.1483

Anterior cruciate ligament (ACL) tears are a common knee injury that can have serious consequences and require medical intervention. Magnetic resonance imaging (MRI) is the preferred method for ACL tear diagnosis. However, manual segmentation of the ACL in MRI images is prone to human error and can be time-consuming. This study presents a new approach that uses deep learning technique for localizing the ACL tear region in MRI images. The proposed multi-scale guided attention-based context aggregation (MGACA) method applies attention mechanisms at different scales within the DeepLabv3+ architecture to aggregate context information and achieve enhanced localization results. The model was trained and evaluated on a dataset of 917 knee MRI images, resulting in 15265 slices, obtaining state-of-the-art results with accuracy scores of 98.63%, intersection over union (IOU) scores of 95.39%, Dice coefficient scores (DCS) of 97.64%, recall scores of 97.5%, precision scores of 98.21%, and F1 Scores of 97.86% on validation set data. Moreover, our method performed well in terms of loss values, with binary cross entropy combined with Dice loss (BCE_Dice_loss) and Dice_loss values of 0.0564 and 0.0236, respectively, on the validation set. The findings suggest that MGACA provides an accurate and efficient solution for automating the localization of ACL in knee MRI images, surpassing other state-of-the-art models in terms of accuracy and loss values. However, in order to improve robustness of the approach and assess its performance on larger data sets, further research is needed.

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