Displaying publications 1 - 20 of 48 in total

Abstract:
Sort:
  1. Unusual presence of Wormian (sutural) bones in human skulls
    Khan AA, Asari MA, Hassan A
    Folia Morphol (Warsz), 2011 Nov;70(4):291-4.
    PMID: 22117248
    Wormian bones are a subset of the small intrasutural bones that lie between the cranial sutures formed by the bones of the skull vault. They are formed due to additional ossification centres in or near sutures. They are usually considered as normal variants and seem to be determined genetically in certain populations. They have been linked with rapid cranial expansion as they appear in great number in hydrocephalic skulls. They are commonly found in the lambdoid suture and fontanelles but are occasionally seen in other sutures especially the coronal, squamosal, and sagittal sutures. We examined 25 dried human skulls with the aim to find out the occurrence and variations of Wormian bones, and surprisingly we found Wormian bones in the coronal, squamosal, and sagittal sutures in 6 skulls. These are uncommon sites of occurrence of sutural bones as reported in the literature. These findings prompted us to report these cases as their presence can lead to confusion in diagnosis in cases of skull fractures.
  2. The sciatic nerve in human cadavers - high division or low formation?
    Khan AA, Asari MA, Pasha MA
    Folia Morphol (Warsz), 2015 12 29;75(3):306-310.
    PMID: 26711654 DOI: 10.5603/FM.a2015.0130
    Variations of the sciatic nerve have been extensively studied in the past including its relationship with the piriformis muscle and associated clinical conditions like piriformis syndrome and sciatica. In the present study we noticed some interesting variations of the sciatic nerve, which were slightly different from the cases described earlier. In the previous studies most of the authors described the higher division of sciatic nerve and none of them discussed its formation. In this study we tried to look its formation from the sacral plexus and its divisions in the thigh. We noticed that in one cadaver the two components of the sciatic nerve originated directly from the sacral plexus and coursed down without merging in the thigh. Should this be called a higher division or non formation of the sciatic nerve? On the other hand in two other cadavers, the two divisions after emerging separately from the sacral plexus, united in the gluteal region and in the thigh respectively. Should we call this as higher division or low formation of the sciatic nerve? In two other cadavers the sciatic nerve emerged from the greater sciatic foramen below the piriformis and divided in the gluteal region itself. Ideally this should be called as higher division of sciatic nerve.
  3. The Impact of Private Standards on Corporate Social Responsibility Compliance and Rural Workers' Motivation in Developing Countries: A Study of Mango Farms in Pakistan
    Tang H, Rasool Z, Khan AI, Khan AA, Khan MA, Azaz GA
    Int J Food Sci, 2021;2021:9985784.
    PMID: 34476257 DOI: 10.1155/2021/9985784
    This study examines the role of a private standard on corporate social responsibility (CSR) compliance in the Pakistani mango industry and how this compliance affects rural workers' motivation. Pakistan is the fifth largest mango producer in the world and the fourth largest exporter in global mango trade; also, mango is the biggest fruit crop within the country. Mango trade is subject to trade terms, where buyers decide the conditions of trade agreements by means of codes of conduct. The key dimensions of the codes involved in agrofood trade are food safety, traceability, worker welfare, and environmental consideration, issues which are all connected with CSR. Private standards ensure compliance with these codes of conduct. This study draws on interviews and a questionnaire survey with certified mango producers and farm workers in Pakistan. The mango industry also involves other stakeholders such as government institutes and NGOs; interviews were also conducted with their representatives. Given that this study is an impact assessment research, the researcher designed a theoretical framework using a mixed method approach to investigate the rationale behind acquiring the standard by the mango growers in Pakistan and what impact (if any) this shift has generated with regard to the farm workers' job satisfaction and motivation. This study is the first to empirically examine good agricultural practices in Pakistan and evaluate their impact. This study shows that private standards play a significant role in ensuring compliance, and CSR practices implemented through them were found to be positively related to the rural workers' job satisfaction and motivation. Furthermore, this study has made separate contributions to theory, methodology, and practice. The production of the synergistic model for improving compliance is among the key highlights of the study. The findings of this study can extend to other agriculture and primary production industry workers in Pakistan and even beyond to other developing countries' rural agriculture workers.
  4. Fulltext Synthesis of diindolylmethane (DIM) bearing thiadiazole derivatives as a potent urease inhibitor
    Taha M, Rahim F, Khan AA, Anouar EH, Ahmed N, Shah SAA, et al.
    Sci Rep, 2020 05 14;10(1):7969.
    PMID: 32409737 DOI: 10.1038/s41598-020-64729-3
    The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1-18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.
  5. Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents
    Ghani U, Syed SA, Aljunidel S, Khan AA, Nur-E-Alam M, AlNoshan A, et al.
    Chem Biodivers, 2024 Feb 23.
    PMID: 38393939 DOI: 10.1002/cbdv.202301399
    Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.
  6. Synthesis of 4-thiazolidinone analogs as potent in vitro anti-urease agents
    Rahim F, Zaman K, Ullah H, Taha M, Wadood A, Javed MT, et al.
    Bioorg Chem, 2015 Dec;63:123-31.
    PMID: 26520885 DOI: 10.1016/j.bioorg.2015.10.005
    4-Thiazolidinone analogs 1-20 were synthesized, characterized by (1)H NMR and EI-MS and investigated for urease inhibitory activity. All twenty (20) analogs exhibited varied degree of urease inhibitory potential with IC50 values 1.73-69.65μM, if compared with standard thiourea having IC50 value of 21.25±0.15μM. Among the series, eight derivatives 3, 6, 8, 10, 15, 17, 19, and 20 showed outstanding urease inhibitory potential with IC50 values of 9.34±0.02, 14.62±0.03, 8.43±0.01, 7.3±0.04, 2.31±0.002, 5.75±0.003, 8.81±0.005, and 1.73±0.001μM, respectively, which is better than the standard thiourea. The remaining analogs showed good to excellent urease inhibition. The binding interactions of these compounds were confirmed through molecular docking studies.
  7. Fulltext Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF
    Khan AA, Huat TJ, Al Mutery A, El-Serafi AT, Kacem HH, Abdallah SH, et al.
    Cell Biosci, 2020;10:126.
    PMID: 33133516 DOI: 10.1186/s13578-020-00487-z
    Introduction: Mesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis.

    Method: Total RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq®500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR.

    Results: In total, of the 3,252 differentially regulated genes between MSCs and NPCs with two or more folds, 1,771 were upregulated genes, whereas 1,481 were downregulated in NPCs. Amongst these differential genes, 104 transcription factors were upregulated, and 45 were downregulated in NPCs. Neurogenesis related genes were upregulated in NPCs and the main non-redundant gene ontology (GO) terms enriched in NPCs were the autonomic nervous system, cell surface receptor signalling pathways), extracellular structure organisation, and programmed cell death. The main non-redundant GO terms enriched in MSCs included cytoskeleton organisation cytoskeleton structural constituent, mitotic cell cycle), and the mitotic cell cycle process Gene set enrichment analysis also confirmed cell cycle regulated pathways as well as Biocarta integrin pathway were upregulated in MSCs. Transcription factors enrichment analysis by ChEA3 revealed Foxs1 and HEYL, amongst the top five transcription factors, inhibits and enhances, respectively, the NPCs differentiation of MSCs.

    Conclusions: The vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.

  8. Fulltext Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation
    Mudassir J, Darwis Y, Muhamad S, Khan AA
    Int J Nanomedicine, 2019;14:4895-4909.
    PMID: 31456636 DOI: 10.2147/IJN.S199507
    Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.
  9. Fulltext Ride or Not to Ride: Does the Customer Deviate toward Ridesharing?
    Shamim A, Khan AA, Qureshi MA, Rafique H, Akhunzada A
    Int J Environ Res Public Health, 2021 10 01;18(19).
    PMID: 34639652 DOI: 10.3390/ijerph181910352
    Traditional taxi services have now been transformed into e-hailing applications (EHA) such as Uber, Careem, Hailo, and Grab Car globally due to the proliferation of smartphone technology. On the one hand, these applications provide transport facilities. On the other hand, users are facing multiple issues in the adoption of EHAs. Despite problems, EHAs are still widely adopted globally. However, a sparse amount of research has been conducted related to EHAs, particular in regards to exploring the significant factors of intention behind using EHAs Therefore, there is a need to identify influencing factors that have a great impact on the adoption and acceptance of these applications. Hence, this research aims to present an empirical study on the factors influencing customers' intentions towards EHAs. The Technology Acceptance Model (TAM) was extended with four external factors: perceived mobility value, effort expectancy, perceived locational accuracy, and perceived price. A questionnaire was developed for the measurement of these factors. A survey was conducted with 211 users of EHAs to collect data. Structural equation modeling (SEM) was used to analyze the collected data. The results of this study exposed that perceived usefulness, perceived price, and perceived ease of use affect behavior intention to use EHAs. Furthermore, perceived ease of use was impacted by effort expectancy, perceived locational accuracy, and perceived mobility. The findings of the study provide a foundation to develop new guidelines for such applications that will be beneficial for developers and designers of these applications.
  10. Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): a narrative review and the implications
    Saleem Z, Godman B, Azhar F, Kalungia AC, Fadare J, Opanga S, et al.
    Expert Rev Anti Infect Ther, 2022 Jan;20(1):71-93.
    PMID: 34038294 DOI: 10.1080/14787210.2021.1935238
    INTRODUCTION: The emergence of antimicrobial resistance (AMR) is a threat to public health. In 2015, the World Health Organization (WHO) introduced a global action plan to tackle AMR in the World Health Assembly. Pakistan's national action plan (NAP) for AMR was released in May 2017 by the Ministry of National Health Services. Based on the NAP, strategies have been initiated on a national and provincial scale in Pakistan.

    AREAS COVERED: This narrative review of the five components of the Pakistan NAP has been undertaken to discuss some of the challenges in implementation of the NAP for AMR in Pakistan including different opinions and views of key stakeholders, combined with suggestions on potential ways to reduce the burden of the AMR.

    EXPERT OPINION: Going forward, healthcare authorities should focus on screening and monitoring of all the objectives of the NAP by establishing proper policies as well as promoting antimicrobial stewardship interventions and Infection prevention and control (IPC) practices. Overall, the comprehensive strengthening of the healthcare system is required to adequately implement the NAP, tackle continued inappropriate antimicrobial use and high AMR rates in Pakistan.

  11. Fulltext Phytochemical characterization and anti-arthritic potential of Croton bonplandianus leaves extract: In-vivo and in-silico approach
    Javed E, Khan HM, Shahzad Q, Shahzad Y, Yasin H, Ul-Haq Z, et al.
    Saudi Pharm J, 2023 Dec;31(12):101860.
    PMID: 38192284 DOI: 10.1016/j.jsps.2023.101860
    Croton bonplandianus, a natural source traditionally used for treating various illnesses, including rheumatoid arthritis, was evaluated in this study. The effects of ethanolic extracts (CBEE) and aqueous fractions (CBAF) of C. bonplandianus leaves on arthritis-induced inflammation were studied using an albino rat model of inflammation induced by Freund's complete adjuvant. Eight test groups (n = 5 per group) and one vehicle control were used to evaluate the antiarthritic effects of different doses of CBEE and CBAF (125 mg.kg-1, 250 mg.kg-1, and 500 mg.kg-1) on days 5, 10, 15, and 20 compared to arthritic and vehicle controls. Arthritis severity was assessed using macroscopic arthritis grading, histological analysis, body weights, and paw thickness. CBEE and CBAF were found to reduce the prevalence of arthritis, increase body weight, and decrease paw inflammation compared to the vehicle control group by the 23rd day. In addition, they showed no effect on biochemical parameters, but a significant difference (p 
  12. Fulltext Phylogeography of the smooth-coated otter (Lutrogale perspicillata): distinct evolutionary lineages and hybridization with the Asian small-clawed otter (Aonyx cinereus)
    Moretti B, Al-Sheikhly OF, Guerrini M, Theng M, Gupta BK, Haba MK, et al.
    Sci Rep, 2017 Jan 27;7:41611.
    PMID: 28128366 DOI: 10.1038/srep41611
    We investigated the phylogeography of the smooth-coated otter (Lutrogale perspicillata) to determine its spatial genetic structure for aiding an adaptive conservation management of the species. Fifty-eight modern and 11 archival (dated 1882-1970) otters sampled from Iraq to Malaysian Borneo were genotyped (mtDNA Cytochrome-b, 10 microsatellite DNA loci). Moreover, 16 Aonyx cinereus (Asian small-clawed otter) and seven Lutra lutra (Eurasian otter) were sequenced to increase information available for phylogenetic reconstructions. As reported in previous studies, we found that L. perspicillata, A. cinereus and A. capensis (African clawless otter) grouped in a clade sister to the genus Lutra, with L. perspicillata and A. cinereus being reciprocally monophyletic. Within L. perspicillata, we uncovered three Evolutionarily Significant Units and proved that L. p. maxwelli is not only endemic to Iraq but also the most recent subspecies. We suggest a revision of the distribution range limits of easternmost L. perspicillata subspecies. We show that smooth-coated otters in Singapore are L. perspicillata x A. cinereus hybrids with A. cinereus mtDNA, the first reported case of hybridization in the wild among otters. This result also provides evidence supporting the inclusion of L. perspicillata and A. cinereus in the genus Amblonyx, thus avoiding the paraphyly of the genus Aonyx.
  13. Outcome of Palliative and Radical Radiotherapy in Patients with Oral Squamous Cell Carcinoma - a Retrospective Study
    Rai NP, Divakar DD, Al Kheraif AA, Ramakrishnaiah R, Mustafa SM, Durgesh BH, et al.
    Asian Pac J Cancer Prev, 2015;16(16):6919-22.
    PMID: 26514468
    BACKGROUND: The treatment selection for the oral squamous cell carcinoma remains controversial. Radiation therapy or surgical excision of the lesion can be applied as the sole treatment or it can be used in combination with other treatment modalities. Radiotherapy is considered to be the safest of all the treatment modalities and can be used in several situations for oral and oropharyngeal cancers. The aim of this study was to evaluate the survival outcome differences in patients treated with radical and palliative radiotherapy as the primary treatment modality.

    MATERIALS AND METHODS: The study included a total of 47 patients with oral cancer reporting to our hospital between years 2009 to 2010. The age group for the selected patients was more than 65 years, treated with radical and palliative radiotherapy with no prior surgical interventions. Patients were evaluated till Dec 2013 for overall survival time.

    RESULTS: Twenty nine patients were treated with radical radiotherapy as main stay of treatment, out of which 21 died during the follow up time with median survival of 352 ± 281.7 days with 8 patients alive. All the 16 patients were dead who received palliative radiotherapy with a median survival time of 112 ± 144.0 days.

    CONCLUSIONS: This retrospective study showed improved overall survival time, loco regional control rates and reduced morbidity in patients treated with radical radiotherapy when compared to patients treated with palliative radiotherapy.

  14. New triazinoindole bearing thiazole/oxazole analogues: Synthesis, α-amylase inhibitory potential and molecular docking study
    Rahim F, Tariq S, Taha M, Ullah H, Zaman K, Uddin I, et al.
    Bioorg Chem, 2019 11;92:103284.
    PMID: 31546207 DOI: 10.1016/j.bioorg.2019.103284
    New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.
  15. New biologically dynamic hybrid pharmacophore triazinoindole-based-thiadiazole as potent α-glucosidase inhibitors: In vitro and in silico study
    Khan AA, Rahim F, Taha M, Rehman W, Iqbal N, Wadood A, et al.
    Int J Biol Macromol, 2022 Feb 28;199:77-85.
    PMID: 34968547 DOI: 10.1016/j.ijbiomac.2021.12.147
    Triazinoindole bearing thiadiazole derivatives (1-25) have been synthesized and characterized through different spectroscopic techniques such as 1H, 13C-NMR and HREI-MS. The purpose of the study was to investigate the anti-diabetic activity of the synthesized triazinoindole bearing thiadiazole derivatives by inhibition of α-glucosidase. All synthesized analogues showed outstanding inhibition of α-glucosidase enzyme with IC50 values ranging from 2.5 ± 0.10 to 38.10 ± 0.10 µM as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Analogue 4 (IC50 = 2.5 ± 0.10 µM) was identifies as the most potent analogue in the series with fifteen folds more active than standard acarbose. Structure activity relationship (SAR) studies suggested that α-glucosidase activities of triazinoindole bearing thiadiazole are primarily dependent upon on number and position of different substitutions present on phenyl parts. Molecular docking study were conducted of the optimized compounds (i.e., compound 4, 6, and 3 etc. using MOE default parameters), the results revealed that compound 4, 6, and 3 showed numerous key interactions with the target protein, which indicate the high potential of these compounds against the target compound. All these compounds were screened for cytotoxic activity against normal normal Vero cell line and found non-toxic.
  16. Fulltext MicroRNA expression profile of bone marrow mesenchymal stem cell-derived neural progenitor by microarray under the influence of EGF, bFGF and IGF-1
    Huat TJ, Khan AA, Abdullah JM, Idris FM, Jaafar H
    Genom Data, 2015 Sep;5:201-5.
    PMID: 26484256 DOI: 10.1016/j.gdata.2015.06.015
    Recently there has been growing interest in the differentiation of mesenchymal stem cells (MSCs) into neural lineages. Research suggests that MSCs can be differentiated into neural progenitor-like cells (NPCs) under the specific influence of paracrine factors particularly epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Our recent research has found that the addition of insulin-like growth factor 1 (IGF-1) with the combination of the EGF and bFGF could significantly improve the growth and survivability of MSC-derived NPCs. To unravel the molecular mechanism of the improved differentiation we compared the microRNA expression profiles of the differentiation under various combinations of growth factors. MSCs were differentiated into neural lineage in 3 groups; Group A (EGF + bFGF), Group B (EGF + bFGF + IGF-1), and Group C (without growth factor). Regulated microRNAs during the early differentiation were identified by detailed microRNA profiling using Affymetrix GeneChip version 2.0 at three time intervals (day 1, day 3 and day 5). The data were deposited in the Gene Expression Omnibus, series GSE60060.
  17. Fulltext MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF
    Huat TJ, Khan AA, Abdullah JM, Idris FM, Jaafar H
    Int J Mol Sci, 2015;16(5):9693-718.
    PMID: 25938966 DOI: 10.3390/ijms16059693
    Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance.
  18. Fulltext Lyophilized Hybrid Nanostructured Lipid Carriers to Enhance the Cellular Uptake of Verapamil: Statistical Optimization and In Vitro Evaluation
    Khan AA, Abdulbaqi IM, Abou Assi R, Murugaiyah V, Darwis Y
    Nanoscale Res Lett, 2018 Oct 15;13(1):323.
    PMID: 30324291 DOI: 10.1186/s11671-018-2744-6
    Verapamil is a calcium channel blocker and highly effective in the treatment of hypertension, angina pectoris, and other diseases. However, the drug has a low bioavailability of 20 to 35% due to the first pass effect. The main objective of this study was to develop hybrid verapamil-dextran nanostructured lipid carriers (HVD-NLCs) in an attempt to increase verapamil cellular uptake. The formulations were successfully prepared by a high-shear homogenization method and statistically optimized using 24 full factorial design. The HVD-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. The results showed that the optimized formula (VER-9) possessed a particle size (PS), polydispersity index (PDI), and the percentage of entrapment efficiency (%EE) of 192.29 ± 2.98, 0.553 ± 0.075, and 93.26 ± 2.66%, respectively. The incorporation of dextran sulfate in the formulation had prolonged the release of verapamil (~ 85% in 48 h) in the simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The differential scanning calorimetry analysis showed no chemical interaction between verapamil and the excipients in the formulation. While wide-angle X-ray scattering studies demonstrated the drug in the amorphous form after the incorporation in the NLCs. The transmission electron microscopy and scanning electron microscopy images revealed that the nanoparticles had spherical shape. The cellular uptake study using Caco-2 cell line showed a higher verapamil uptake from HVD-NLCs as compared to verapamil solution and verapamil-dextran complex. The optimized formulation (VER-9) stored in the refrigerated condition (5 °C ± 3 °C) was stable for 6 months. In conclusion, the HVD-NLCs were potential carriers for verapamil as they significantly enhanced the cellular uptake of the drug.
  19. Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake
    Khan AA, Akhtar S, Yadav Y, Atiya A, Alelwani W, Bannunah AM, et al.
    Curr Drug Deliv, 2023;20(10):1474-1486.
    PMID: 35980056 DOI: 10.2174/1567201819666220817111054
    BACKGROUND: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.

    METHODS: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.

    RESULTS: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).

    CONCLUSION: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.

  20. Letter to the editor: Cardiovascular risk prediction with cardio-ankle vascular index in the Malaysian cohort study
    Burki AUH, Khan AA, Ashraf DA, Rizvi A, Hassan S
    Curr Probl Cardiol, 2024 Apr;49(4):102462.
    PMID: 38346612 DOI: 10.1016/j.cpcardiol.2024.102462
Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links